Stress Echocardiography Research Articles

Long-Term outcomes after stress echocardiography in real world practice: five-year follow-up of the UK Evarest study.

Stress echocardiography is widely used to assess patients with chest pain. The clinical value of a positive or negative test result to inform on likely longer-term outcomes when applied in real world practice across a healthcare system has not been previously reported. 5503 patients recruited across 32 UK NHS hospitals between 2018 and 2022, participating in the EVAREST/BSE-NSTEP prospective cohort study, with data on medical outcomes up to 2023 available from NHS England were included in analysis. Stress echocardiography results were related to outcomes, including death, procedures, hospital admissions and relevant cardiovascular diagnoses, based on Kaplan-Meier analysis and Cox proportional hazard ratios. Median follow-up was 829 days (IQR 224-1434). A positive stress echocardiogram was associated with a greater risk of myocardial infarction (HR 2.71, 95% CI 1.73-4.24, P<0.001), and a composite endpoint of cardiac-related mortality and myocardial infarction (HR 2.03, 95% CI 1.41-2.93, P<0.001). Hazard ratios increased with ischaemic burden. A negative stress echocardiogram identified an event-free 'warranty period' of at least five years in patients with no prior history of coronary artery disease, and four years for those with disease. In real-world practice, the degree of myocardial ischaemia recorded by clinicians at stress echocardiography correctly categorises risk of future events over the next five years. Reporting a stress echocardiogram as negative correctly identifies patients with no greater than a background risk of cardiovascular events over a similar time period.

Abstract 4121840: Contemporary Safety of Ultrasound Enhancing Agents in a Nationwide Analysis

Background: Ultrasound enhancing agents (UEAs) are an important diagnostic tool for transthoracic or stress echocardiography (TTE/SE) but recent concerns have been raised about their safety in reports from individual health systems. Objectives: To identify if UEAs for TTE/SE are associated with serious adverse events within 48 hours of receipt in nationwide claims data. Methods: All-payor nationwide claims from 320 million insured individuals across the US, 2018-2022 from the Komodo Health database were used to evaluate rates of death or the composite of death, anaphylaxis, MI, coronary angiography, PCI, CABG, ventricular tachycardia or cardiac arrest within 48 hours of UEA receipt for TTE/SE among adults. Propensity score matching (PSM) was used to account for baseline imbalances. Results: Of the 11,421,463 individuals included (mean age 57.5 ± 16.2, 54.0% female, 46.2% White), a total of 500,073 (4.4%) received TTE/SE with UEAs. Individuals receiving Lumason™ or Definity™ more frequently had TTEs/SEs performed in the emergency department/inpatient setting and had more comorbidities than those receiving Optison™. After PSM, the odds of death were lower in those receiving UEAs (receipt vs. non-receipt, 0.02% vs. 0.14%, OR 0.23, 95% CI 0.19-0.28, p &lt; 0.001) and were similar across agents ( Table; Definity™: 0.02%, OR 0.22, 95% CI 0.18-0.28; Lumason™: 0.03%, OR 0.33, 95% CI 0.18-0.28; Optison™: 0.01%, OR 0.17, 95% CI 0.08-0.38; all p &lt; 0.001). Rates of the composite outcome were essentially unchanged after excluding claims for anaphylaxis. Rates of all outcomes were stable across study years, including considering pre-COVID (2018-2019) and post-COVID (2020-2022) periods. Conclusions: In this large nationwide claims analysis from 2018-2022, serious adverse events from UEAs for TTE/SE were uncommon and overall similar across agents and years of study. Receipt of UEAs was associated with a lower odds of death at 48 hours.

Abstract 4124430: Calcinosis Cutis and Heart Failure---A Rare Manifestation Which Should Never Be Ignored!

Introduction: Heart failure can be a manifestation of underlying immune mediated myopathies like dermatomyositis/polymyositis which can present in broad range of clinical manifestations and sometimes dermatologic lesions can be the only manifestation of these underlying pathologies without typically involving the muscle weakness. Calcinosis cutis is the deposition of calcium salts in the skin and subcutaneous tissue. There are five subtypes of calcinosis cutis, dystrophic, metastatic, idiopathic, iatrogenic and calciphylaxis. Case summary: 70-year-old female was evaluated for bilateral lower extremity swelling. Past medical history was significant for Graves’ disease, atrial fibrillation, mechanical aortic valve on warfarin, hypertension, hyperlipidemia, ascending aortic aneurysm. Work up showed BNP of 4700 pg/ml with normal cardiac enzymes. Transthoracic echocardiogram revealed newly reduced ejection fraction of 25—30% with severely dilated left ventricle. Patient refused cardiac catheterization. Nuclear stress test showed no evidence of ischemia. Patient was started on guideline directed medical therapy and biventricular Implantable cardioverter defibrillator device was placed as per cardiology recommendation. Six months later patient developed multiple calcinosis cutis lesions on abdominal wall requiring surgical excisions. Endocrine work up including PTH, serum Ca level was normal, however creatin kinase level was high normal (150 U/L). Serum aldolase was ordered which was found to be elevated(25U/L). Muscle biopsy was performed as per recommendations of rheumatology which was diagnostic of dermatomyositis. Patient was started on high dose steroids and methotrexate and eventually IV immunoglobulins as per rheumatology recommendation. Follow up echocardiogram revealed improved ejection fraction to 40--45% with resolution of any further lesion of calcinosis cutis afterwards. Conclusion: Cardiac involvement such as congestive heart failure can be a part of presentation of underlying untreated myopathies. Calcinosis cutis can be the only clinical manifestation of dermatomyositis affecting heart. Etiology of calcinosis cutis in patients with heart failure should be worked up properly. Dystrophic calcinosis cutis is the subtype associated with underlying autoimmune connective tissue diseases.

Abstract 4144526: A Case Presentation of Severe Left Ventricular Dysfunction from Focal Myocarditis due to Immune Checkpoint Inhibitor

Introduction: Immune checkpoint inhibitors (ICI), such as pembrolizumab, are an effective immunotherapy for several malignancies, however, have been associated with adverse events including myocarditis and accelerated atherosclerosis. ICI myocarditis is associated with a mortality rate of up to 33%. This case reports a patient on pembrolizumab with an atypical presentation. Case presentation: A 75-year-old female with a past medical history significant for lung cancer on pembrolizumab and myasthenia gravis presented to the hospital with dyspnea and mild, intermittent exertional chest discomfort. She denied nausea, radiation of pain, diplopia, weakness in extremities, or dysphagia. Workup revealed a leucocyte count of 13,500 cells/uL, pro-brain natriuretic peptide of 13,458 pg/mL, troponin of 26 ng/L, and a normal erythrocyte sedimentation rate and C reactive protein. A chest computed tomography was performed that showed mild bilateral pleural effusion and no pulmonary embolism. A nuclear stress test showed no evidence of ischemia but showed a severely reduced left ventricular ejection fraction (LVEF) at 29%. An echocardiogram confirmed that the ejection fraction was reduced at 23% (baseline LVEF was 60% from 1 year ago). Cardiac MRI revealed a mildly increased regional T2 signal in the anterolateral wall, mildly elevated extracellular volume fraction, and no late gadolinium enhancement. With ongoing clinical suspicion despite equivocal findings on cardiac MRI, an endomyocardial biopsy was done that revealed a single small aggregate of lymphocytes present in 1 of 6 tissue samples. Ultimately, with the single site of aggregated lymphocytes on biopsy, a diagnosis of ICI myocarditis was determined, and the patient was started on high-dose intravenous glucocorticoids as well as bisoprolol, empagliflozin, spironolactone, and Entresto for heart failure management as she was able to tolerate. Discussion: Myocarditis due to pembrolizumab is a rare, but potentially lethal adverse effect. Patients typically have abnormal electrocardiograms and elevated cardiac biomarkers. Cardiac MRIs have sensitivity and specificity of 68% and 91% respectively for diagnosis, and the gold standard is endomyocardial biopsy however, it is limited due to sampling error. Our patient had an unusual presentation, but with both imaging and biopsy, we found a case of focal myocarditis with severe left ventricular dysfunction, which typically is seen with fulminant myocarditis.

Abstract 4118444: Right Ventricular Contractile Reserve and Right Ventricular-Pulmonary Arterial Coupling Are Impaired in Long-Term Survivors of Childhood Cancers

Background: Childhood cancer survivors are at risk of right ventricular (RV) dysfunction in relation to cardiac toxicity due to chemotherapy and radiation therapy. This study tested the hypothesis that RV contractile reserve and RV-pulmonary arterial (PA) coupling are altered in long-term survivors of childhood cancers. Methods: Thirty survivors (60% men) aged 24.3 ± 5.2 years at 15.3 ± 6.3 years after completion of chemotherapy and thirty healthy control subjects (47% men) were studied. Resting and submaximal supine bicycle stress echocardiography was performed for assessment of RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), left ventricular (LV) and RV longitudinal strain, mitral and tricuspid annular velocities and myocardial acceleration during isovolumic contraction (IVA). The slope of the RV force-frequency relationship was derived from the change in IVA with the change in heart rate during exercise (△IVA/△heart rate), while RV-PA coupling was determined by the ratio between TAPSE and pulmonary arterial acceleration time indexed to RV ejection time (PAATi). Results: At rest, tricuspid annular systolic velocity and RV systolic strain were significantly lower in survivors ( P &lt; 0.05 for both), while RV FAC, TAPSE and IVA were similar between the two groups ( P &gt; 0.05 for all). During submaximal exercise testing, all RV systolic functional indices were significantly lower in survivors than controls ( P &lt; 0.05 for all). The slope of the RV force-frequency relationship was significantly flatter in survivors compared to controls (0.038 ± 0.002 vs 0.059 ± 0.003 m/sec 2 beats/min, P &lt; 0.001). For RV-PA coupling, TAPSE/PAATi was similar between survivors and controls at baseline but became significantly lower in survivors during submaximal exercise ( P = 0.002). Conclusions: The RV contractile reserve and RV-PA coupling are impaired during exercise in long-term survivors of childhood cancers. Future studies aimed at determining the clinical and prognostic significance of these impairments are warranted.

Abstract 4115015: Hyperpolarized Carbon-13 Metabolic Imaging Detects Changes in Cardiac Mitochondrial Metabolism in Patients Before and After Coronary Artery Bypass Graft Surgery

Background: Coronary Artery Disease (CAD) is a significant global health issue, necessitating improved diagnostic tools for visualizing cardiac energetics. Traditional imaging methods such as PET and dobutamine stress echocardiography do not directly assess mitochondrial metabolism. Hyperpolarized Carbon-13 metabolic magnetic resonance imaging (HP- 13 C MRI) offers a promising non-invasive method for investigating mitochondrial function in CAD. This study utilizes HP- 13 C MRI to detect changes in mitochondrial metabolism in patients undergoing Coronary Artery Bypass Graft (CABG) surgery (Fig.1). Methods: We conducted HP- 13 C MRI examinations on two patients with advanced CAD before and (~4-6 months after CABG surgery and one healthy subject (Fig. 2 A,B). Participating subjects provided informed consent according to a protocol approved by the Institutional Review Board and Protocol Review Committee. Baseline blood samples were analyzed for pyruvate, triglycerides, free fatty acids, and insulin levels. Post-glucose load, patients received an intravenous injection of an IND-approved metabolic probe, [1- 13 C] pyruvic acid, prepared under Good Manufacturing Practice regulations. The HP solution was administered after polarization in a clinical polarizer (SPINlab™, GE Healthcare). Imaging was performed using a GE MR750 MR system with a Helmholtz loop-pair 13 C coil (PulseTeq Limited, UK). Data were reconstructed and analyzed with MATLAB scripts. Results and Discussion: Baseline blood measurements were normal for the healthy subject, but those with advanced CAD showed variable and abnormal values (Fig. 2C). HP- 13 C MRI safely assessed cardiac metabolism in patients with advanced CAD. Patients with advanced CAD exhibited reduced pyruvate metabolism compared to healthy controls, shown by lower myocardial bicarbonate/(bicarbonate+lactate) ratios (Bic/(Bic+Lac)). Following CABG, only Patient 2 showed improved Bic/(Bic+Lac), while Patient 1 did not (Fig. 3A-B). This variability may be influenced by differences in nutrition, hormonal status, medication regimens, or other factors. Changes in % Bic/(Bic+Lac) across different coronary artery segments were observed post-CABG in CAD patients (Fig. 3C). Conclusion: HP- 13 C MRI non-invasively assesses cardiac metabolism in CAD patients, demonstrating the potential to evaluate post-CABG metabolic changes. Our efforts continue to recruit large cohort to understand individual variability.

Abstract 4138517: Role of Coronary Computed Tomographic Angiography in Patients with Discordant Findings on Exercise Stress Echocardiography

Background: Exercise stress echocardiography is routinely used for risk stratification and diagnosis of myocardial ischemia in low-to-intermediate risk patients with suspected coronary artery disease (CAD). Discrepancies between exercise electrocardiography (EKG) and echocardiography (ECHO) are common in clinical practice. Prior literature suggests that patients with discordant stress test results generally have worse outcomes, though the extent of epicardial atherosclerotic disease remains unclear. Coronary computed tomographic angiography (CTA) has gained a class I recommendation for the assessment of atherosclerotic burden per ACC/AHA chest pain guidelines. Using non-invasive fractional flow reserve (CT-FFR), the functional significance of lesions can also be assessed. This study investigates the incidence and burden of CAD in patients with discordant exercise echocardiography findings. Methods: Patients aged 18 or older who had exercise echocardiography followed by CTA from January 1, 2013, to January 31, 2023, were retrospectively enrolled in this study and categorized into two discordant result groups: EKG+/ECHO- or EKG-/ECHO+. Those who failed to achieve the target heart rate or had a paced rhythm/left bundle branch block on baseline EKG were excluded. CTA findings were classified as no CAD, non-obstructive CAD (&lt;50% stenosis), obstructive CAD (≥50% stenosis), and obstructive CAD with FFR+ (&lt;0.75). Results: The study included 198 patients, the majority female (56.0%), with a mean age of 61 ±10 years. Among them, 159 (80.3%) were EKG+/ECHO- and 39 (19.7%) were EKG-/ECHO+ (Table 1). In the EKG+/ECHO- group, 55 (34.6%) had no CAD, 48 (30.2%) had non-obstructive CAD, and 56 (35.2%) had obstructive CAD, out of which 19 (33.9%) were FFR+. In the EKG-/ECHO+ group, 13 (33.3%) had no CAD, 17 (43.6%) had non-obstructive CAD, and 9 (23.2%) had obstructive CAD of which 3 (33.3%) was FFR+. There was no statistically significant difference in the degree of CAD between the two cohorts. Conclusions: The majority of patients with discordant results on exercise echocardiography were found to have CAD. There was no significant difference in the degree of disease between the EKG+/ECHO- or EKG-/ECHO+ groups. Overall, discordant results on exercise echocardiography should not be discounted and warrant further evaluation. CTA provides important information that can impact the diagnosis and further medical management of patients with chest pain and suspected CAD.

Catheter ablation of atrial fibrillation in women with heart failure with preserved ejection fraction

BackgroundHeart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) often coincide. Female sex is associated with both increased prevalence of HFpEF and reduced therapeutic efficacy of catheter ablation of AF. This sub-analysis of the previously published AFFECT-study evaluates outcome after cryoballoon-ablation in women with and without HFpEF.MethodsOne-hundred-and-two patients (LVEF ≥ 50%) scheduled for cryoballoon-ablation of AF were prospectively enrolled. Forty-two were female. Comprehensive baseline assessment included echocardiography, stress echocardiography, six-minute-walk-test, biomarker- and quality-of-life-assessment (QoL, SF-36), and was repeated at follow-up ≥12 months after AF-ablation. Baseline parameters, procedural characteristics and outcome after AF-ablation were compared between women with and without HFpEF.ResultsWomen with HFpEF (n = 20) were characterized by higher median left atrial volume index (35.8 ml/m2 vs. 25.8 ml/m2, P &amp;lt; 0.001), left ventricular hypertrophy (median left ventricular mass index: 92.0 g/m2 vs. 83.0 g/m2, P = 0.027), reduced distance in the 6-min-walk-test (median: 453 m vs. 527 m, P = 0.008) and higher left atrial pressures (median: 14.0 mmHg vs.9.5 mmHg, P = 0.008) compared to women without HFpEF (n = 21). During follow-up, HFpEF-patients more often experienced AF-related re-hospitalization (36.8% vs. 9.1%, P = 0.039) and numerically higher AF-recurrence-rates (57.9% vs. 31.1%, P = 0.109). There was no significant improvement of heart failure-related symptoms, echocardiographic parameters and cardiac biomarkers levels. QoL showed no significant improvement in both subgroups. Women with HFpEF still exhibited a lower SF-36 Physical Component Summary Score vs. women without HFpEF (median: 41.2 vs. 52.1, P &amp;lt; 0.001).ConclusionWomen with HFpEF constitute a distinct subgroup with high rates of AF-related events after AF-ablation, and persistence of both symptoms and functional hallmarks of HFpEF. Consideration of sex-specific cardiac co-morbidities is crucial for personalization and optimization of AF-therapy.Clinical Trial RegistrationClinicalTrials.gov Identifier NCT05603611.

An Unexpected Finding in an Adolescent Rowing Athlete With Angina Pectoris. A Case Report.

Significant intraventricular gradient development during exercise is rare, usually occurring with left ventricular hypertrophy. The etiopathogenesis consists of the increase in nonobstructive physiological gradients; ventricular cavitary obliteration with consequent end-systolic obstruction; and midsystolic obstruction caused by systolic anterior movement of the mitral valve compromising flow. A correlation between intraventricular gradient development and various symptoms has been established. Chest pain is common in children and is a frequent reason for referral to pediatric cardiologists. Despite the benign nature of most pediatric chest pain, extensive and costly cardiac evaluation is common in these patients. In the case presented here, we describe an adolescent rowing athlete with excruciating effort angina only during upright exercise, which was replicated while performing an exercise stress echocardiography.

Left atrial function during exercise stress echocardiography as a sign of paroxysmal/persistent atrial fibrillation

ObjectiveAtrial cardiomyopathy is closely associated with atrial fibrillation (AF), and some patients exhibit no dysfunction at rest but demonstrate evident changes in left atrial (LA) function and LA volume during exercise. This study aimed to identify distinguishing signs during exercise stress echocardiography (ESE) among patients in sinus rhythm (SR), with and without history of paroxysmal/persistent AF (PAF).MethodsA prospective cohort of 1055 patients in SR was enrolled across 12 centers. The main study cohort was divided into two groups: the modeling group (n = 513) and the verification group (n = 542). All patients underwent ESE, which included B-lines, LA volume index (LAVi), and LA strain of the reservoir phase (LASr).ResultsAge, resting and stress LAVi and LASr, and B-lines were identified as a combination of detectors for PAF in both groups. In the entire cohort, aside from resting and stress LAVi and LASr, additional parameters differentiating PAF and non-PAF patients were the presence of systemic hypertension, exercise E/e’ > 7, worse right ventricle (RV) contraction during exercise (∆ tricuspid annular plane systolic excursion < 5 mm), a lower left ventricular contractile reserve (< 1.6), and a reduced chronotropic reserve (heart rate reserve < 1.64). The composite score, summing all 9 items, yielded a score of > 4 as the best sensitivity (79%) and specificity (65%).ConclusionESE can complement rest echocardiography in the identification of previous PAF in patients with SR through the evaluation of LA functional reservoir and volume reserve, LV chronotropic, diastolic, and systolic reserve, and RV contractile reserve.Graphical A scoring system predicting the probability of PAF. The score was computed using the cutoff values as in the illustration. The score >4 demonstrated a sensitivity of 79% and a specificity of 65% of PAF.

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&amp;lt;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 (&amp;gt;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&amp;lt;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 &amp;gt;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&amp;lt;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&amp;lt;0.01) and admissions for HF (24% vs. 5%, p &amp;lt;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 &amp;lt; 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&amp;gt;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 &amp;lt;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 &amp;lt;2.0 (HR 2.58, 95% CI 1.65-4.04; p&amp;lt;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 &amp;lt;2.0 and 2.7% in those with no RWMA and CFVR &amp;gt;2.0 (Figure, p&amp;lt;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 (&amp;gt;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&amp;lt;0.001, respectively). High CAVI (≥8.5), resting GLS in the LAD(&amp;lt;-15.5%), and peak GLS during stress (&amp;lt;-15.3%) emerged as significant ischemic threshold predictors in multivariate analysis (AUC = 0.82, p&amp;lt;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=&amp;lt;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=&amp;lt;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&amp;lt;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.