Stress Echocardiography Testing Research Articles

Combined use of stress echocardiography and cardiopulmonary exercise testing to assess exercise intolerance in patients treated for acute myocardial infarction.

Exercise intolerance after acute myocardial infarction (AMI) is a predictor of worse prognosis, but its causes are complex and poorly studied. This study assessed the determinants of exercise intolerance using combined stress echocardiography and cardiopulmonary exercise testing (CPET-SE) in patients treated for AMI. We prospectively enrolled patients with left ventricular ejection fraction (LV EF) ≥40% for more than 4 weeks after the first AMI. Stroke volume, heart rate, and arteriovenous oxygen difference (A-VO2Diff) were assessed during symptom-limited CPET-SE. Patients were divided into four groups according to the percentage of predicted oxygen uptake (VO2) (Group 1, <50%; Group 2, 50–74%; Group 3, 75–99%; and Group 4, ≥100%). Among 81 patients (70% male, mean age 58 ± 11 years, 47% ST-segment elevation AMI) mean peak VO2 was 19.5 ± 5.4 mL/kg/min. A better exercise capacity was related to a higher percent predicted heart rate (Group 2 vs. Group 4, p <0.01), higher peak A-VO2Diff (Group 1 vs. Group 3, p <0.01) but without differences in stroke volume. Peak VO2 and percent predicted VO2 had a significant positive correlation with percent predicted heart rate at peak exercise (r = 0.28, p = 0.01 and r = 0.46, p < 0.001) and peak A-VO2Diff (r = 0.68, p <0.001 and r = 0.36, p = 0.001) but not with peak stroke volume. Exercise capacity in patients treated for AMI with LV EF ≥40% is related to heart rate response during exercise and peak peripheral oxygen extraction. CPET-SE enables non-invasive assessment of the mechanisms of exercise intolerance.

Characterization of hemodynamic and metabolic abnormalities in the heart failure spectrum: the role of combined cardiopulmonary and exercise echocardiography stress test.

Heart failure (HF) is a complex clinical syndrome characterized by different etiologies and a broad spectrum of cardiac structural and functional abnormalities. Current guidelines suggest a classification based on left ventricular ejection fraction (LVEF), distinguishing HF with reduced (HFrEF) from preserved (HFpEF) LVEF. HF should also be thought of as a continuous range of conditions, from asymptomatic stages to clinically manifest syndrome. The transition from one stage to the next is associated with a worse prognosis. While the rate of HF-related hospitalization is similar in HFrEF and HFpEF once clinical manifestations occur, accurate knowledge of the steps and risk factors leading to HF progression is still lacking, especially in HFpEF. Precise hemodynamic and metabolic characterization of patients with or at risk of HF may help identify different disease trajectories and risk factors, with the potential to identify specific treatment targets that might offset the slippery slope towards overt clinical manifestations. Exercise can unravel early metabolic and hemodynamic alterations that might be silent at rest, potentially leading to improved risk stratification and more effective treatment strategies. Cardiopulmonary exercise testing (CPET) offers valuable aid to investigate functional alterations in subjects with or at risk of HF, while echocardiography can assess cardiac structure and function objectively, both at rest and during exercise (exercise stress echocardiography [ESE]). The purpose of this narrative review was to summarize the potential advantages of using an integrated CPET-ESE evaluation in the characterization of both subjects at risk of developing HF and patients with stable HF.

The role of contractile reserve by stress test echocardiography for predicting cardiac resynchronization therapy responder: systematic review and meta-analysis

Introduction: Up to one-third of patients who received resynchronization devices do not experience full benefit of cardiac resynchronization therapy (CRT). Echocardiography plays an important role in heart failure patients treated with CRT. Contractile reserved is a strong prognostic factor to predict positive response to CRT (CRT responder).&#x0D; Objective: We perform a systematic review and meta-analysis of published data to assess the relationship between contractile reserve (CR) and response to CRT.&#x0D; Methods: We conduct a systematic search from major medical databases on all clinical trials published up to June 2020, written in English, full-text availability, and human subject. We used Newcastle-Ottawa Scale to measure the quality of evidence. We employed the Mantel–Haenszel random-effects meta-analysis of using RevMan 5.4.&#x0D; Results: We identified 17 studies involving 1399 patients. The type of stress was either dobutamine (n=15) or exercise (n=2). The presence of CR was associated with a higher chance of CRT responder (OR 7.68, 95%CI 4.27–13.82, p&lt;0.001) using a random-effects model. The ORs slightly differed when studies were analyzed separately based on the stress test type and definition of CR. Contractile reserve, assessed with dobutamine stress echocardiography (DSE), defined as an increase in LVEF (OR 5.10, 95% CI 2.29–11.32, P &lt;0.00001) was numerically lower than defined as increased LV contractility (OR 6.86, 95% CI 3.36–12.88, P &lt;0.00001). The presence of CR assessed with exercise stress test are associated with higher chance of CRT responder (OR 49.11, 95% CI 15.04–160.36, P &lt;0.00001). From our meta-analysis, we found non-ischemic has better respond to CRT compare to patient with ischemic etiology (OR 0.41; 95% CI 0.31-0.55, P &lt;0.01).&#x0D; Conclusion: The presence of CR during stress test echocardiography with either dobutamine or exercise stress test is associated with a higher chance of CRT responder.

Predicting heart failure transition and progression: a weighted risk score from bio-humoral, cardiopulmonary and echocardiographic stress testing

Abstract Funding Acknowledgements Type of funding sources: None. Aims. We tested the prognostic role of a risk score including bio-humoral evaluation, cardiopulmonary-echocardiographic stress (CPET-ESE) and lung ultrasound, in patients with heart failure (HF) with reduced and preserved ejection fraction (HFrEF and HFpEF), and subjects at risk of developing HF (American College of Cardiology/American Heart Association Stages A and B). Methods and results. We evaluated 318 subjects: 94 in Stages A-B, 194 in Stage C (85 HFpEF and 109 HFrEF), and 30 age and sex-matched controls (Stage 0). During a median follow-up of 18.5 months, we reported 40 urgent HF visits, 31 HF hospitalisations and 10 cardiovascular deaths. Cox proportional-hazards regression for predicting adverse events identified five independent predictors and each was assigned a number of points proportional to its regression coefficient: Δstress-rest B-lines &amp;gt;10 (3 points), peak oxygen consumption &amp;lt;16 mL/kg/min (2 points), minute ventilation/carbon dioxide production slope ≥36 (2 points), peak systolic pulmonary artery pressure ≥50 mmHg (1 point) and resting N-terminal pro-brain natriuretic peptide (NT-proBNP) &amp;gt;900 pg/mL (1 point). We defined three risk categories: low-risk (&amp;lt;3 points), intermediate-risk (3-6 points), and high-risk (&amp;gt;6 points). The event-free survival probability for these three groups were 93%, 52% and 20%, respectively. Hazard Ratio was 4.55 for each risk category upgrade (95% confidence interval [CI], 3.44-5.93). The area-under-curve for the scoring system to predict events was 0.92 (95% CI 0.88-0.96). Conclusion. A multiparametric risk score including indices of exercise-induced pulmonary congestion, markers of cardiopulmonary dysfunction and NT-proBNP identifies patients at increased risk for HF events across the HF spectrum. Table 1 Variable EPYC score EPYC score &amp;lt;3 (low risk) n = 217 EPYC score 3-6 (intermediate risk) n = 70 EPYC score &amp;gt;6 (high risk) n = 31 p-value (between risk categories) Event-free (n = 244) 0 (0 - 2) 210 (97) 32 (46) 2 (6) &amp;lt;0.0001 With events (n = 74) 6 (4 - 9) 7 (3) 38 (54) 29 (94) &amp;lt;0.0001 p-value (event-free vs with events) &amp;lt;0.0001 &amp;lt;0.0001 &amp;lt;0.0001 &amp;lt;0.0001 Stage 0-Controls (n = 30) 0 (0 - 1) 30 0 0 &amp;lt;0.0001 Stages A-B (n = 94) 1 (0 - 2) 85 (45) 6 (9) 3 (10) &amp;lt;0.0001 Stage C-HFpEF (n = 85) 3 (1 - 6)*† 46 (25) 29 (41) 10 (32) &amp;lt;0.0001 Stage C-HFrEF (n = 109) 4 (2 - 7)*† 56 (30) 35 (50) 18 (58) &amp;lt;0.0001 p-value (between HF Stages) &amp;lt;0.0001 &amp;lt;0.0001 &amp;lt;0.0001 &amp;lt;0.0001 Values are mean ± standard deviation, n (%), or median [25th quartile, 75th quartile]. * p &amp;lt; 0.01 vs Stage 0-Controls; † p &amp;lt; 0.01 vs Stages A-B. Abstract Figure 1

Additional prognostic value of vasodilator stress CMR in patients with inconclusive stress test to detect coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Guidelines recommend performing a non-invasive testing for ischemia to diagnose coronary artery disease (CAD). However, these tests are frequently inconclusive (25%). This population has been poorly studied because of its heterogeneity. In such cases, stress cardiac magnetic resonance (CMR) may be useful to improve diagnostic certainty. To date, no study has evaluated the prognostic value of stress CMR in these patients presenting with prior inconclusive test. PURPOSE To assess the additional prognostic value of vasodilator stress perfusion CMR in patients with a first inconclusive stress test to detect CAD. METHODS Between 2008 and 2018, consecutive patients with inconclusive stress test prospectively referred for vasodilator stress perfusion CMR with dipyridamole were followed for major adverse cardiovascular events (MACE) defined as cardiac death or myocardial infarction. Inconclusive stress test was defined by echocardiography or nuclear stress testing with uncertain conclusion about the diagnosis of CAD. To characterize this population, an unsupervised clustering analysis was performed using 18 variables. Univariable and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia by stress CMR in each cluster. RESULTS Of 1502 patients with inconclusive stress test (62 ± 12 years, 59% men), 1441 (96%) completed the CMR protocol and 1397(93%) completed the follow-up (median 5.5 ± 2.3 years). Stress CMR was well tolerated without occurrence of death or severe adverse event. The clustering analysis identified 3 clusters: Cluster 1 (n = 524, 35%) had the highest prevalence of previous percutaneous coronary intervention (PCI), the highest presence of myocardial scar on CMR, the lowest LVEF(35 ± 7%) and the highest degree of LV dilatation. Cluster 2 (n = 406, 27%) had the highest prevalence of previous coronary artery bypass grafting (CABG), preserved LVEF(54 ± 10%), absence of LV dilatation and rate of male(89%). Cluster 3 (n = 572, 38%) had the lowest rate of previous PCI/CABG and of myocardial scar. This cluster gathered the oldest patients (73 ± 11 years), predominantly female (60%), with the highest rate of atrial fibrillation and body mass index. Survival analysis found significant differences across clusters for the occurrence of MACE (p = 0.02). Moreover, inducible ischemia was significantly associated with the occurrence of MACE in each cluster (cluster 1, HR 2.28; [95%CI: 1.31-3.99]; p = 0.0028; cluster 2, HR 3.37; [95%CI, 1.97-5.75]; p &amp;lt; 0.0001; cluster 3, HR 2.73; [95%CI, 1.67-4.46]; p &amp;lt; 0.0001). In multivariable Cox regression, inducible ischemia was an independent predictor of a higher incidence of MACE in each cluster (p &amp;lt; 0.001). CONCLUSIONS Cluster analysis identified 3 different phenotypes of patients with inconclusive stress test that were associated with distinct clinical and prognostic profiles. Within these clusters, CMR stress has an additional prognostic value to predict the occurrence of MACE. Abstract Figure. Kaplan-Meier for MACE in each cluster

Cardiac reserve and exercise capacity: insights from combined cardiopulmonary and exercise echocardiography stress testing

Abstract Funding Acknowledgements Type of funding sources: None. Aims. Combined cardiopulmonary exercise test (CPET) and exercise stress echocardiography (ESE) provides a non-invasive tool to study cardiopulmonary pathophysiology. We analyzed how cardiac functional reserve during exercise relates to peak oxygen consumption (VO2). Methods and Results. We performed a symptom-limited graded ramp bicycle CPET-ESE in 30 healthy controls and 357 patients: 113 at risk of developing heart failure (American College of Cardiology/American Heart Association HF Stages A-B) and 244 in HF Stage C with preserved (HFpEF, n = 101) or reduced ejection fraction (HFrEF, n = 143). Peak VO2 significantly decreased from controls to Stage A-B and Stage C (Table 1). A multivariable regression model to predict peak VO2 revealed peak left ventricular systolic annulus tissue velocity (S"), peak TAPSE/PAPs (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) and low-load left atrial reservoir strain/E/e’ were independent predictors, in addition to peak heart rate, stroke volume and workload (adjusted R²=0.76, p &amp;lt; 0.0001). The model was successfully tested in subjects with atrial fibrillation (n = 49), and with (n = 224) and without (n = 163) beta-blockers (all p &amp;lt; 0.01). Peak S’ showed the highest accuracy in predicting peak VO2 &amp;lt; 10 mL/kg/min (cut-point ≤ 7.5 cm/s; AUC = 0.92, p &amp;lt; 0.0001) and peak VO2 &amp;gt; 20 mL/kg/min (cut-point &amp;gt; 12.5 cm/s; AUC = 0.84, p &amp;lt; 0.0001) in comparison to the other cardiac variables of the model (p &amp;lt; 0.05). Conclusions. A model incorporating different measures of cardiac mechanics is strongly related to peak aerobic capacity and may help in identifying different causes of effort intolerance from HF Stage A to C. Table 1 Variable Overall population (n = 387) Controls (n = 30) Stage A-B (n = 113) Stage C-HFpEF (n = 101) Stage c-HFrEF (n = 143) p-value Age, years 68.9 ± 11.1 67.1 ± 10.6 67.7 ± 10.4 70.5 ± 10.1 68.5 ± 11 0.1 Male, n (%) 247 (64) 18 (60) 70 (62) 57 (56) 102 (71) 0.1 VO2 @peak, mL/min/kg 15.7 (12.1-19.6) 23 (21.7- 29.7) 18 (15.4- 20.7)* 13.6 (11.8- 16.8)*† 14.2 (10.7- 17.5)*† &amp;lt;0.0001 Workload @peak, W 90 (65-120) 130 (115-195) 110 (84-130)* 70 (55-100)*† 80 (60-110)*† &amp;lt;0.0001 Heart rate @peak, bpm 123 ± 22 142 ± 12 130 ± 20* 115 ± 17*† 119 ± 23*† &amp;lt;0.0001 Stroke volume @peak, mL 83 (71-99) 98 (85-114) 86 (76-107) 83 (74-97)* 75 (63-95)*† &amp;lt;0.0001 Average S" @peak, cm/s 11.2 ± 3.8 17.1 ± 3.9 13.3 ± 2.9* 10.6 ± 2.5*† 8.7 ± 2.7*†‡ &amp;lt;0.0001 TAPSE/PAPs @peak, mm/mmHg 0.75 (0.46-0.97) 1.05 (0.93- 1.16) 0.81 (0.52- 0.91)* 0.52 (0.38- 0.83)*† 0.58 (0.41- 0.89)*† &amp;lt;0.0001 Left atrial reservoir strain/E/e" @low-load, % 2.25 (1.17-5.04) 6.23 (4.45-6.77) 4.34 (3.89- 5.58)* 2.23 (1.31- 2.86)*† 1.91 (1.07-2.44)*†‡ &amp;lt;0.0001 * p &amp;lt; 0.01 vs Controls; † p &amp;lt; 0.01 vs Stage A-B; ‡ p &amp;lt; 0.01 vs Stage C-HFpEF. PAPs systolic pulmonary artery pressure; TAPSE: tricuspid annular plane systolic excursion; VO2: oxygen consumption. Abstract Figure 1

Rest NT-proBNP but not MR-proANP predicts positive diastolic stress echocardiography test result in patients with preserved left ventricle ejection fraction and heart failure symptoms

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Silesia Introduction Diastolic dysfunction and heart failure (HF) with preserved ejection fraction are diagnostic challenges in rest transthoracic echocardiography (TTE) and clinical practice. The aim of our study was to evaluate the clinical value of diastolic stress echocardiography (DSE) and its corelation with NT-proBNP and MR-proANP testing in patients with preserved left ventricle ejection fraction (LVEF) and HF symptoms. Methods: All the consecutive patients with HF symptoms, preserved LVEF and suspected diastolic dysfunction were examined with DSE with the protocol according to the EACVI 2016 recommendations. Patients with cardiomyopahties, significant valve defects or extracardiac diseases causing similar symptoms were excluded. The assessment of diastolic function was obtained at rest transthoracic echocardiography (TTE) and at peak exertion in DSE: left atrium volume index (LAVI), average E/e’ &amp;gt;14, peak tricuspid regurgitation velocity &amp;gt;2,8 m/s, septal e’ velocity &amp;lt;7 cm/s or lateral e’&amp;lt; 10cm/s (&amp;gt;50% positive – diastolic dysfunction). Moreover, blood samples for NT-proBNP and MR-proANP were taken just before and 30 minutes after DSE. Results The study group included 80 patients (age: 69 ± 8.3 years; 24% males) with dyspnea (NYHA IIa – 53pts; IIb – 17pts; III – 10pts) and risk factors: hypertension (77pts), diabetes (33pts), known coronary artery disease (8pts) and chronic kidney disease (21pts). The rest TTE showed preserved systolic function (LVEF 61.6 ± 8.8%) and normal or indeterminate diastolic function in all patients. DSE revealed positive result for diastolic dysfunction in 17 patients (21%). The levels of NT-proBNP :267(160-518) vs 310(172-522) (p = 0.46) and MR-proANP: 16,2(7,8-542) vs 14,7(6,1-646) p = 0,38 did not significantly change before and after DSE. The ROC analysis showed that age (AUC = 0.720; p &amp;lt; 0.001), LAVI rest (AUC = 0.722, p &amp;lt; 0.01), E/e’ rest (AUC 0.790;p &amp;lt; 0.001) and baseline NT-proBNP (AUC 0.770; p = 0.002) predicted positive DSE. Other parameters, including BMI, baseline E/A, DT or e’ and MR-proANP were not predictive for DSE result. There was a positive correlation between stress NTproBNP and stress LAVI (r = 0.3;p &amp;lt; 0.05) and stress E/e’ (r = 0.5; p &amp;lt; 0.05) There wasn’t such correlation between MRproANP and stress LAVI and stress E/e’. Conclusions Diastolic stress echocardiography revealed diastolic dysfunction in 21% of study patients and improved the diagnostic value of echocardiography. Rest NT-proBNP but not rest MR-proANP predicted positive DSE.

Cardiovascular effects of COVID-19 lockdown in professional football players.

The COVID-19 pandemic with the stay-at-home orders and lockdown has dramatically forced athletes to stop team training and competitions, causing deep changes in habits and lifestyle. Aim of this study was to evaluate in a retrospective single center study the cardiovascular (CV) health and fitness of elite football player after COVID-19 lockdown in Italy and to compare such findings with the 2019 off-season period, in order to identify potential differences in the CV features and outcomes. All 29 professional football players of the first male team were enrolled before resuming training and competition after COVID-19 lockdown and underwent several exams including physical examination, resting and stress electrocardiography (ECG), echocardiography, spirometry and blood tests. Median age was 27 years (23; 31), with no athlete being COVID-19 positive at the time of the evaluation. In comparison with the usual off-season 2-month detraining, significant differences were found for left ventricular (LV) mass (189 g [172; 212] vs. 181 g [167; 206], P=0.024) and LV Mass Index for body surface area (94 g/m2 [85; 104] vs. 88 g/m2 [79.5; 101.5], P=0.017), while LV mass/fat free mass remained unchanged (2.8 g/kg [2.6; 2.9] vs. 2.9 g/kg [2.6; 3.2], P=0.222). Respiratory function and metabolic profile were improved, while no significant changes were found in ECG findings, at rest and during exercise. Prolonged abstinence from training and competitions induced by lockdown elicited significant changes in comparison with off-season in parameters ascribable to detraining, as the changes in LV mass, in respiratory function and in metabolic profile.

Impact of left atrial strain mechanics on exercise intolerance and need for septal reduction therapy in hypertrophic cardiomyopathy.

We sought to assess the relationship between left atrial (LA) strain mechanics and exercise intolerance, and to evaluate the prognostic impact of LA strain mechanics on clinical deterioration necessitating septal reduction therapy in hypertrophic cardiomyopathy (HCM). Consecutive HCM patients who underwent exercise stress echocardiography and cardiopulmonary exercise testing on the same day between October 2015 and April 2019 were enrolled prospectively. LA strain mechanics were analysed using speckle tracking echocardiography. LA stiffness was calculated as the ratio of E/e' ratio to LA reservoir strain. The study cohort was divided into four groups based on the quartile of percent-predicted peak VO2, and exercise intolerance was defined as the lowest quartile (≤51%). Of 532 patients studied (mean age: 51 ± 15 years, 42% female), 138 patients demonstrated exercise intolerance. As exercise capacity worsened, LA strain mechanics worsened along a continuum (P < 0.001). LA contractile strain with a cut-off of -13.9% was optimal at identifying exercise intolerance. On multivariable analysis, worse LA contractile strain was an independent predictor for exercise intolerance (P = 0.002). Of patients with left ventricular outflow tract obstruction, patients with LA stiffness worse than the median value (≥0.41) were significantly more likely to require septal reduction therapy than those with better LA stiffness (P = 0.026). Worse LA contractile strain was an independent predictor for exercise intolerance in HCM. Patients with worse LA stiffness had a higher probability of clinical deterioration necessitating septal reduction therapy.

Additional prognostic value of vasodilator stress cardiovascular magnetic resonance in patients with inconclusive stress test to detect coronary artery disease

Guidelines recommend performing a non-invasive testing for ischemia to diagnose coronary artery disease (CAD). However, these tests are frequently inconclusive (25%). To assess the additional prognostic value of vasodilator stress perfusion CMR in patients with a first inconclusive stress test to detect CAD. Between 2008 and 2018, consecutive patients with inconclusive stress test to detect CAD prospectively referred for vasodilator stress perfusion CMR with dipyridamole were followed for major adverse cardiovascular events(MACE) defined as cardiac death or myocardial infarction. Inconclusive stress test was defined by stress echocardiography or nuclear stress testing with uncertain conclusion. To characterize this population, an unsupervised clustering analysis of these patients was performed using 18 variables. Univariable and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia in each of the clusters identified. Of 1502 patients with inconclusive stress test (62 ± 12 years, 59% men), 1397 (93%) completed the follow-up (median 5.5 ± 2.3 years). Stress CMR was well tolerated without severe adverse event. An unsupervised clustering analysis of those patients identified 3 clusters:. – Cluster 1 (n = 524, 35%) had the highest prevalence of previous PCI, the highest presence of a myocardial scar defined by CMR, the lowest LVEF (35 ± 7%) and the highest degree of LV dilatation. – Cluster 2 ( n = 406, 27%) had the highest prevalence of previous CABG (82%), preserved LVEF(54 ± 10%), absence of LV dilatation, and presence of myocardial scar(52%). This cluster comprised predominantly male patients (89%), with the highest rate of dyslipidemia(81%) or hypertension(71%). – Cluster 3 ( n = 572, 38%) had the lowest rate of previous PCI/CABG (9%) and the lowest rate of myocardial scar in CMR(6%). This cluster gathered the oldest patients(73 ± 11 years) and was predominantly female(60%) with the highest rate of atrial fibrillation(51%) or body mass index. Survival analysis found significant differences across clusters for the occurrence of MACE ( P = 0.02). Moreover, the presence of inducible ischemia was significantly associated with the occurrence of MACE in each cluster (cluster 1, hazard ratio HR 2.28; [95% confidence interval CI: 1.31–3.99]; P = 0.0028; cluster 2, HR 3.37; [95%CI, 1.97–5.75]; P < 0.0001; cluster 3, HR 2.73; [95%CI, 1.67–4.46]; P < 0.0001). In a multivariable Cox regression including clinical characteristics and CMR indexes, the presence of inducible ischemia was an independent predictor of a higher incidence of MACE in each cluster ( P < 0.001 for all) ( Fig. 1 ) Cluster analysis of clinical and CMR variables identified 3 different phenotypes with distinct clinical and prognostic profiles. Within these clusters, CMR stress has an additional prognostic value to predict MACE.

Clustering for identification of patients with inconclusive non-invasive testing for ischaemia to detect coronary artery disease

Guidelines recommend performing a non-invasive testing for ischemia to diagnose coronary artery disease (CAD). However, these tests are frequently inconclusive (20–30%) and can lead to uncertainty about the likelihood of CAD. This population has been poorly studied because it is a heterogeneous population difficult to characterise. To characterise a population of patients with inconclusive test using an unsupervised classification algorithm, then to compare the prognosis of each clusters identified. Between 2008 and 2018, consecutive patients with inconclusive stress test to detect CAD prospectively referred for a second stress test were followed for major adverse cardiovascular events (MACE) defined as cardiac death or non-fatal myocardial infarction (MI). Inconclusive stress test was defined by stress echocardiography or nuclear stress testing with uncertain conclusion. Data were analysed by a hierarchical clustering on principal components (HCPC) to perform this unsupervised classification algorithm. Among baseline, clinical and CMR characteristics, 18 variables were used for the clustering of patients. Of 1502 patients with inconclusive stress test (61.9 ± 11.8 years, 59% men), 1397 (93%) completed the follow-up (median 5.5 ± 2.3 years). An unsupervised clustering analysis of those patients identified 3 clusters of phenotypes: cluster 1 ( n = 524, 35%) had the highest prevalence of previous PCI (59%), the highest presence of a myocardial scar defined by CMR (58%), the lowest LVEF (35 ± 7%) and the highest degree of LV dilatation (LVEDVi = 124 ± 25 mL/m 2 ). Cluster 2 ( n = 406, 27%) had the highest prevalence of previous CABG (82%), preserved LVEF (54 ± 10%), absence of LV dilatation (LVEDVi = 82 ± 20 mL/m 2 ), and presence of myocardial scar defined by CMR (52%). This cluster comprised predominantly male patients (89%), with the highest rate of dyslipidemia (81%) or hypertension (71%). Cluster 3 ( n = 572, 38%) had the lowest rate of previous CABG or PCI (9%) and the lowest rate of myocardial scar in CMR (6%). This cluster gathered the oldest patients (73 ± 11 years) and was predominantly female (60%) with the highest rate of atrial fibrillation (51%) or body mass index (31 ± 7.8 kg/m 2 ). Survival analysis found significant differences across clusters for the occurrence of MACE ( P = 0.02) et cardiovascular mortality ( P < 0.0001) ( Fig. 1 ). Using Cox proportional hazards modelling, clusters 1 (hazard ratio: 0.72; 95% confidence interval: 0.50 to 1.04) and 3 (hazard ratio: 0.62; 95% confidence interval: 0.30 to 1.25) had a similar prognostic, which was better than cluster 2 (HR: 1.00 [reference]). Cluster analysis of clinical and CMR variables identified 3 different phenotypes of patients with inconclusive stress test to detect CAD that were associated with distinct clinical and prognostic profiles.

Impact of Medicare Benefits Schedule (MBS) Item Number Changes on Cardiac Investigations (Plain Echocardiography, Stress Echocardiography, Electrocardiography Stress Testing)

Cardiac investigations are one of the most common investigations conducted in Australia. The Australian Government Department of Health has introduced changes to item numbers in the Medicare Benefits Schedule (MBS) for Plain echocardiography, Stress echocardiography and Electrocardiography Stress Testing, effective from 1 August 2020. The major change is that these investigations cannot be claimed if done in previous 24 months.

A novel numerical model of combination levels of C-peptide and insulin in coronary artery disease risk prediction.

Insulin resistance is a major risk factor for coronary artery disease (CAD). The C-peptide-to-insulin ratio (C/I) is associated with hepatic insulin clearance and insulin resistance. The current study was designed to establish a novel C/I index (CPIRI) model and provide early risk assessment of CAD. A total of 865 adults diagnosed with new-onset diabetes mellitus (DM) within one year and 54 healthy controls (HC) were recruited to develop a CPIRI model. The CPIRI model was established with fasting C/I as the independent variable and homeostasis model assessment of insulin resistance (HOMA-IR) as the dependent variable. Associations between the CPIRI model and the severity of CAD events were also assessed in 45 hyperglycemic patients with CAD documented via coronary arteriography (CAG) and whom underwent stress echocardiography (SE) and exercise electrocardiography test (EET). Fasting C-peptide/insulin and HOMA-IR were hyperbolically correlated in DM patients and HC, and log(C/I) and log(HOMA-IR) were linearly and negatively correlated. The respective correlational coefficients were -0.83 (p < 0.001) and -0.76 (p < 0.001). The equations CPIRI(DM) = 670/(C/I)2.24 + 0.25 and CPIRI(HC) = 670/(C/I)2.24 - 1 (F = 1904.39, p < 0.001) were obtained. Patients with insulin resistance exhibited severe coronary artery impairment and myocardial ischemia. In CAD patients there was no significant correlation between insulin resistance and the number of vessels involved. CPIRI can be used to effectively evaluate insulin resistance, and the combination of CPIRI and non-invasive cardiovascular examination is of great clinical value in the assessment of CAD.

Preconception consultation using treadmill exercise stress echocardiography for pregnant women with the left-sided heart valve stenosis: A preliminary report.

Pregnancy can increase gradients across the heart valves and consequently deteriorates maternal and fetoneonatal conditions. Hence, pregnancy during heart valve diseases can be challenging and we need to risk stratify patients before conception. We tried to assess the role of preconception consultation using treadmill stress echocardiography (TSE) testing for identifying pregnancy outcomes in women with mitral valve stenosis (MS) or aortic valve stenosis (AS). Pregnant patients with a diagnosis of MS or AS were evaluated from January 2015 to December 2018. First group included patients undergoing the TSE testing and they were permitted to get pregnant if they met pre-defined criteria. Second group comprised women who did not undergo TSE testing. Maternal and fetoneonatal outcomes were also recorded. A total of 29 and 18 patients with MS and AS, respectively, were recruited. Among MS patients, individuals without TSE had more functional deterioration (11.1% vs. 35%) and more fetoneonatal events (FNE) (22.2% vs. 55%) compared with those undergoing TSE. The rates of maternal events and mitral valvuloplasty during pregnancy were significantly higher in patients without TSE compared with those undergoing TSE (p=0.015 and p=0.042, respectively). Among AS patients, maternal and FNE were higher in patients without TSE compared with those undergoing TSE, but those were comparable. Pregnant patients with the left-sided valvular stenosis who received preconception TSE testing had better outcomes compared with those who did not undergo preconception consultation. This underscores the utility of stress echocardiography in the risk stratification of pregnancies.

Predicting the transition to and progression of heart failure with preserved ejection fraction: a weighted risk score using bio-humoural, cardiopulmonary, and echocardiographic stress testing.

Risk stratification of heart failure (HF) patients with preserved ejection fraction (HFpEF) can promote a more personalized treatment. We tested the prognostic value of a multi-parametric evaluation, including biomarkers, cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE), and lung ultrasound, in HFpEF patients and subjects at risk of developing HF (HF Stages A and B). Risk stratification of heart failure (HF) patients with preserved ejection fraction (HFpEF) can promote a more personalized treatment. We tested the prognostic value of a multi-parametric evaluation, including biomarkers, cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE), and lung ultrasound, in HFpEF patients and subjects at risk of developing HF (HF Stages A and B). We performed a resting clinical/bio-humoural evaluation and a symptom-limited CPET-ESE in 274 patients (45 Stage A, 68 Stage B, and 161 Stage C-HFpEF) and 30 age- and sex-matched healthy controls. During a median follow-up of 18.5 months, we reported 71 HF hospitalizations and 10 cardiovascular deaths. Cox proportional-hazards regression identified five independent predictors and each was assigned a number of points proportional to its regression coefficient: stress-rest ΔB-lines >10 (3 points), peak oxygen consumption <16 mL/kg/min (2 points), minute ventilation/carbon dioxide production slope ≥36 (2 points), peak systolic pulmonary artery pressure ≥50 mmHg (1 point) and resting N-terminal pro-brain natriuretic peptide (NT-proBNP) >900 pg/mL (1 point). The event-free survival probability for low risk (<3 points), intermediate risk (3-6 points), and high risk (>6 points) were 93%, 52%, and 20%, respectively. The area under the curve (AUC) for the scoring system to predict events was 0.92 (95% CI 0.88-0.96), with an accuracy significantly higher than the individual components of the score (all P < 0.01 vs. individual AUCs). A weighted risk score including NT-proBNP, markers of cardiopulmonary dysfunction and indices of exercise-induced pulmonary congestion identifies HFpEF patients at increased risk for adverse events and Stage A and B subjects more likely to progress towards more advanced HF stages.

Abstract 16032: Determinants of Exercise Capacity Assessed Using Combined Stress Echocardiography and Cardiopulmonary Exercise Testing in Patients Treated for Acute Myocardial Infarction

Introduction: Exercise capacity (EC) after acute myocardial infarction (AMI) influences prognosis, but the causes of its reduction are complex and not sufficiently studied. Methods: We prospectively enrolled consecutive patients who underwent percutaneous coronary intervention for their first AMI without residual coronary stenosis and with left ventricular ejection fraction (LVEF) &gt; 40% more than 4 weeks after the AMI. We performed combined stress echocardiography and cardiopulmonary exercise testing (CPET-SE) using a semi-supine cycle ergometer to determine predictors of EC (peak oxygen uptake [VO 2 ]). Results: Among 81 patients (70% male, mean age 58 ± 11 years), 40% suffered AMI with ST-segment elevation (STEMI), and 60% non-STEMI, LVEF was 57 ± 7%; wall motion score index, 1.18 (IQR 1.06 - 1.31); peak VO 2 , 19.5 ± 5.4 mL/kg/min. Multivariate analysis ( Table ) revealed that parameters at peak exercise: heart rate (β = 0.17, p &lt; 0.001), stroke volume (β = 0.09, p &lt; 0.001), and arteriovenous oxygen difference (β = 93.51, p &lt; 0.001) were independently positively correlated with peak VO 2 , with arteriovenous oxygen difference being its strongest contributor. At rest, left ventricular systolic and diastolic function parameters and the extent of myocardial scarring (wall motion score index) did not predict EC (p &gt; 0.05). Conclusions: In patients treated for AMI with normal/mildly reduced LVEF, EC is associated with peak peripheral oxygen extraction as well as peak heart rate and peak stroke volume. CPET-SE is a useful tool to evaluate decreased fitness in this group.

Abstract 13038: Utility of Left Atrial Strain Mechanics and Stiffness in Patients With Hypertrophic Cardiomyopathy

Introduction: Llittle is known about the relationship between LA strain mechanics and exercise intolerance in hypertrophic cardiomyopathy (HCM), or whether LA strain mechanics might serve as novel imaging markers in predicting the need for septal myectomy. Hypothesis: LA mechanical dysfunction would be associated with impaired exercise capacity and clinical deterioration necessitating septal myectomy in HCM. Methods: Consecutive patients with HCM who underwent exercise stress echocardiography and cardiopulmonary exercise testing between October 2015 and April 2019 were enrolled prospectively. LA structure parameters (maximum and minimum LA volume indices) and LA function parameters were measured. LA strain mechanics (reservoir, conduit and contractile strains) were analyzed by speckle tracking echocardiography. LA stiffness was calculated as the ratio of E/e’ to reservoir strain. Based on the quartile of percent-predicted peak VO 2 , the study cohort was divided into four groups. Exercise intolerance was defined as the lowest quartile of percent-predicted peak VO 2 (≤52%). Results: Of 536 HCM patients studied (mean age: 51 ± 15 years, 42% female), 212 (40%) demonstrated exercise intolerance. Receiver operating characteristics analysis demonstrated LA contractile strain, using a cut-off of 13.8%, to be optimal for predicting exercise intolerance (AUC: 0.68, p &lt;0.001). On multivariable logistic regression analysis, impaired LA contractile strain was an independent predictor for exercise intolerance (p &lt;0.001). Among 258 patients who were followed up at our center, patients with LA stiffness worse than the median value (≥0.41) had significantly higher probability of requiring myectomy, compared with those with LA stiffness below the median (p = 0.02, Figure ). Conclusions: Impaired LA contractile strain was an independent predictor of exercise intolerance in HCM. Patients with worse LA stiffness were more likely to require septal myectomy.

Abstract 13471: Additional Prognostic Value of Vasodilator Stress Cardiovascular Magnetic Resonance in Patients With Inconclusive Stress Test to Detect Coronary Artery Disease

Introduction: Non-invasive testing for ischemia to diagnose coronary artery disease(CAD) are frequently inconclusive(25%). Hypothesis: To assess the prognostic value of stress CMR in patients with a first inconclusive stress test. Methods: Between 2008 and 2018, consecutive patients with inconclusive stress test, defined by stress echocardiography or nuclear testing with uncertain conclusion, prospectively referred for stress CMR with dipyridamole were followed for major adverse cardiovascular events(MACE): cardiac death or myocardial infarction. An unsupervised clustering analysis was performed. Results: Of 1502 patients (62±12yrs, 59%men), 1397 completed the follow-up (median 5.5±2.3yrs). Three clusters were identified: Cluster 1 (n=524) had the highest prevalence of previous PCI, the highest presence of a myocardial scar defined, the lowest LVEF (35±7%) and the highest LV dilatation. Cluster 2 (n=406) had the highest previous CABG prevalence, preserved LVEF, absence of LV dilatation, and presence of myocardial scar. This cluster comprised predominantly male patients, with the highest rate of hypertension. Cluster 3 (n=572) had the lowest rate of previous PCI/CABG, the lowest rate of myocardial scar, predominantly female, the highest atrial fibrillation rate and body mass index. Survival analysis found significant differences across clusters for the occurrence of MACE (p=0.02). Inducible ischemia was associated with MACE occurrence in each cluster (C1, HR 2.28; 95%CI[1.31-3.99]; p=0.0028; C2, HR 3.37; 95%CI[1.97-5.75]; p&lt;0.0001; C3, HR 2.73; 95%CI[1.67-4.46]; p&lt;0.0001). In multivariable analysis, inducible ischemia predicted MACE in each cluster (p&lt;0.001 for all). Conclusions: Cluster analysis identified 3 different phenotypes with distinct clinical and prognostic profiles. Within these clusters, stress CMR has an additional prognostic value to predict MACE..

Aortic stiffness and distensibility in elite athletes: impact of discipline and gender

Abstract Background Aortic remodeling in athletes is variable among sports disciplines with more ascending aorta (Asc Ao) dilatation in endurance (EAs) as compared to power athletes (PAs). Nevertheless, the impact of this differential remodeling on the Asc Ao functional properties is not well established. The aim of this study was to assess the distensibility and stiffness of the ascending aorta in endurance and power elite athletes in order to evaluate if this aortic remodeling implies functional changes. Methods 119 elite athletes (61 EA and 58 PA, 49% female sex, mean age: 18.7±7.1 years) underwent standardized pre-participation screening with 12 lead ECG, transthoracic echocardiography and maximum stress test. Asc Ao diameter was measured from parasternal long axis views in 2D echocardiography. The aortic distensibility index (ADi) was calculated as 2 × (systolic Asc Ao diameter − diastolic Asc Ao diameter) / (diastolic Asc Ao diameter) × (pulse pressure) (cm–2 dyn–1 10–6). Aortic stiffness (AS) index was defined as Ln (systolic blood pressure/diastolic blood pressure) / (systolic Asc Ao diameter − diastolic Asc Ao diameter)/diastolic proximal Asc Ao diameter. Results Globally, EA presented larger AscAO, both in absolute and indexed values, than PA (28±3.0 vs 26±3.0cm, p&amp;lt;0.001 and 16.4±1.5 vs 15.7±1.9cm, p&amp;lt;0.05, while were no differences in AS or ADi) (Figure 1A). Nevertheless, ADi in male EAs was higher than in male PAs (ADi: 4.3±1.7 vs 3.2±1.3 cm2/dyn/10–6, p&amp;lt;0.05) and AS was lower (AS: 4.7±1.7 vs 6.3±3.8, P&amp;lt;0.005) (Figure 1B and 1C). Female athletes presented higher ADi (ADi: 4.7±1.9 vs 4.0±1.6 cm, p&amp;lt;0.05) and a trend towards lower AS (4.8±2.9 vs 5.1±2.6, p: 0.4) than male athletes. There were no differences in AS or ADi between female EAs and PAs. Conclusion Male EAs showed an increased aortic distensibility with lower stiffness as compared to that observed in male PAs. This difference was not observed in female EAs and PAs, potentially due to better baseline distensibility with less room for improvement with endurance training. Funding Acknowledgement Type of funding source: None

Additional prognostic value of vasodilator stress CMR in patients with inconclusive stress test to detect coronary artery disease

Abstract Background Guidelines recommend performing a non-invasive testing for ischemia to diagnose coronary artery disease (CAD). However, these tests are frequently inconclusive (25%). This population has been poorly studied because of its heterogeneity. In such cases, stress cardiac magnetic resonance (CMR) may be useful to improve diagnostic certainty. To date, no study has evaluated the prognostic value of stress CMR in these patients presenting with prior inconclusive test. Purpose To assess the additional prognostic value of vasodilator stress perfusion CMR in patients with a first inconclusive stress test to detect CAD. Material Between 2008 and 2018, consecutive patients with inconclusive stress test prospectively referred for vasodilator stress perfusion CMR with dipyridamole were followed for major adverse cardiovascular events (MACE) defined as cardiac death or myocardial infarction. Inconclusive stress test was defined by echocardiography or nuclear stress testing with uncertain conclusion about the diagnosis of CAD. To characterize this population, an unsupervised clustering analysis was performed using 18 variables. Univariable and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia by stress CMR in each cluster. Results Of 1502 patients with inconclusive stress test (62±12 years, 59% men), 1441 (96%) completed the CMR protocol and 1397 (93%) completed the follow-up (median 5.5±2.3 years). Stress CMR was well tolerated without occurrence of death or severe adverse event. The clustering analysis identified 3 clusters: Cluster 1 (n=524, 35%) had the highest prevalence of previous percutaneous coronary intervention (PCI), the highest presence of myocardial scar on CMR, the lowest LVEF (35±7%) and the highest degree of LV dilatation. Cluster 2 (n=406, 27%) had the highest prevalence of previous coronary artery bypass grafting (CABG), preserved LVEF (54±10%), absence of LV dilatation and rate of male (89%). Cluster 3 (n=572, 38%) had the lowest rate of previous PCI/CABG and of myocardial scar. This cluster gathered the oldest patients (73±11 years), predominantly female (60%), with the highest rate of atrial fibrillation and body mass index. Survival analysis found significant differences across clusters for the occurrence of MACE (p=0.02). Moreover, inducible ischemia was significantly associated with the occurrence of MACE in each cluster (cluster 1, HR 2.28; [95% CI: 1.31–3.99]; p=0.0028; cluster 2, HR 3.37; [95% CI, 1.97–5.75]; p&amp;lt;0.0001; cluster 3, HR 2.73; [95% CI, 1.67–4.46]; p&amp;lt;0.0001). In multivariable Cox regression, inducible ischemia was an independent predictor of a higher incidence of MACE in each cluster (p&amp;lt;0.001). Conclusions Cluster analysis identified 3 different phenotypes of patients with inconclusive stress test that were associated with distinct clinical and prognostic profiles. Within these clusters, CMR stress has an additional prognostic value to predict the occurrence of MACE. Kaplan-Meier for MACE in each cluster Funding Acknowledgement Type of funding source: None