The International Stress Echo Study to to Define the Future of Imaging
Status: Recruiting
Location: See location...
Intervention Type: Diagnostic test
Study Type: Observational
SUMMARY
With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2- SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4- SE post-chest radiotherapy and chemotherapy (SERA); 5- Artificial intelligence SE evaluation (AI-SEE); 6- Environmental stress echocardiography and air pollution (ESTER); 7- SE in repaired Tetralogy of Fallot (SETOF) ; 8- SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10- SE for mitral ischemic regurgitation (SEMIR); 11- SE in valvular heart disease (SEVA); 12- SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021-2025) ≥10 000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time and in any patient.
Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 75
View:
• Known or suspected coronary artery disease Hypertrofic cardiomiopathy Repaired Tetralogy of Fallot Primary valvular disease
Locations
Other Locations
Italy
Fatebenefratelli Hospital
RECRUITING
Benevento
Contact Information
Primary
Quirino Ciampi, MD
qciampi@gmail.com
+393389166076
Time Frame
Start Date: 2021-04-01
Estimated Completion Date: 2030-12-31
Participants
Target number of participants: 10000
Treatments
ABCDE-Stress Echo in Coronary Artery Disease (SECAD project)
All patients with known or suspected CAD will be evaluated with ABCDE-SE. Patients will be referred according to existing 2020 guidelines indication; status post heart transplant; pediatric patients and congenital heart disease ; peri-partum cardiomyopathy. Information on demographics, lifestyle and other risk factors and ongoing therapy will be collected. Data related to carotid disease and cardiac calcification will be collected. All patients will enter a regular clinical follow-up program with annotation of cardiovascular and non-cardiovascular endpoints, such as cancer or neurodegenerative disease, characterized by endothelial dysfunction (step D positivity) and autonomic dysfunction (step E positivity). A sample size of about 2 430 patients with a 5-year follow-up is required to provide 90% power with an alpha error of 5% to detect a difference for the primary endpoint of all-cause mortality among those with positive versus negative SE also considering a 20% drop-out.
ABCDE-Stress Echo in Diastolic Heart failure (SEDIA project)
Patients with dyspnea and known or suspected heart failure with preserved ejection fraction by 2019 European Society of Cardiology criteria will be enrolled and studied with cycle-ergometer in semi-supine SE (or treadmill). A score of at least 1 according to the criteria proposed by Pieske et al. is required for inclusion. In patients unable to exercise or did not allow sampling of CFVR, pharmacological test (vasodilator or dobutamine) is recommended. Assuming that the hypothesis of proportionality of hazard holds, as required for Cox proportional hazards regression, with a power of 90%, an attrition rate of 10% and a 5-year follow-up period of a sample size of 181 patients is required.
ABCDE-Stress Echo in Hypertrophic Cardiomyopathy (SEHCA project)
The primary aim is to evaluate the feasibility of comprehensive ABCDEFG-SE in the evaluation of HCM. The secondary aim is to assess the value of each of obtaained parameters in predicting response to specific therapy and other interventions. The tertiary aim is to assess the prognostic value of SE indices for prognostic stratification in the medium-long-term. HCM diagnosis will be based on existing guidelines. All patients will be followed-up. In patients and first-degree relatives with genetic characterization different phenotypes will be correlated with specific genotypes. Non-imaging or routine imaging non-ultrasound exams will be collected and analyzed with neural network analysis developed in project 5. We assume that a sample size of 338 patients is required.
ABCDE-Stress Echo post-Radiotherapy (SERA project)
Radiation-induced heart disease is associated with a significantly higher morbidity and mortality in cancer patients. The most frequent forms treated with chest radiation therapy are breast, lung, and esophageal cancers or lymphoma. The chances of developing radiation-induced heart disease increase with higher cumulative doses (\>30 Gray) in anterior or left sided irradiation, concomitant chemotherapy, presence of cardiovascular risk factors, and increased distance from time of irradiation. The estimated incidence of major cardiac events related to ischemic heart disease is 30% at 10 years post-treatment in female patients with radiotherapy post-breast cancer. The resulting epicardial artery stenosis, low grade inflammation , myocardial fibrosis, microvascular injury , alterations in autonomic balance, valve leaflets, and accelerated calcification can lead to significant alteration of all SE steps. A sample size of 507 patients is required and will be enrolled.
ABCDE- Artificial Intelligence Stress echo (AI-SEE)
The project have 2 separate aims: AI-SEE images: To make SE reading operator-independent for each of the essential reading steps (from A to E). AI-SEE data: To identify the links between clinical imaging and stress variables and develop a tailored personalized model for risk prediction. For each parameter assessment (positivity versus negativity), the area under the receiver-operating characteristic curve produced by the deep learning algorithm will be compared to that produced by the experienced cardiologist (cross-sectional analysis). AI-SEE images: a set of images from 1 250 patients from at least 10 laboratories will be sufficient to develop the algorithm (modeling set) subsequently prospectively tested on a different set of 1250 patients (validation set). AI-SEE data: a set of data from 2 500 patients from at least 10 laboratories will be sufficient to develop the algorithm (modeling set) subsequently tested on a different set of 2 500 patients (validation set).
ABCDE- Environmental Stress Echocardiography, air pollution and medical radiation (ESTER project)
The primary aim is to assess the inter-patient correlation between SE results and outdoor air pollution levels in patients matched for clinical, coronary anatomy (if available) and resting functional features. Secondary aim is to assess the effects of air quality and cumulative medical radiation exposure in prognostic modeling using traditional risk factors and SE results. All patients enrolled in projects 1 to 4 have information on house residency and work place in the data bank. The air epidemiology unit will obtain same day local air quality data from publicly available data sets from regional authority of environmental protection. For each patient and each test of the same patient, the values of 2 particulate and 4 gaseous pollutants will be collected when available. Data on medical radiation exposure will also be systematically collected. Of the 2 430 tests recruited in protocol 1, at least 600 will have access to geo-referenced air quality data.
SETOF Stress Echo in operated Tetralogy of Fallot.
The primary aim is to evaluate the feasibility of right ventricular SE in patients with repaired Tetralogy of Fallot. The secondary aim is to assess the presence and amount of right ventricular contractile reserve and its correlation with indices of functional severity (NYHA class, cardiac natriuretic peptides, peak VO2, 6-min walking test, etc.). The tertiary aim is to assess the prognostic value of SE indices for prognostic stratification in the medium and long-term. Patients with repaired Tetralogy of Fallot or Fallot-like pathology evaluated at least 1 year after the last surgical or percutaneous procedure, will be recruited by regional reference centers for congenital heart disease. Additional inclusion criteria are age\>10 years, height\>140 cm, NYHA class I or II. Data on medical radiation exposure will also be systematically collected. A sample size of about 250 patients is required to detect a significant stress-induced increase in tricuspid annular plane systolic excursion.
Stress Echo for surveillance post-COVID-19 (SECOV).
Cardiovascular abnormalities are observed in half of all COVID-19 patients and may range from RWMA to interstitial lung disease with alveolar capillary distress, global contractile dysfunction, coronary microvascular abnormalities and cardiac autonomic dysfunction. In addition, pulmonary hypertension and valves abnormalities are a possible consequence. The primary aim is to assess the feasibility of an integrated ABCDEFG approach in post-COVID 19 patients. Secondary aim is to prevalence of abnormalities of different SE parameters in populations stratified according to severity of COVID-19. Tertiary aim is to assess the prognostic value of individually considered or combined SE indices in prognostic modeling using traditional risk factors and COVID-19 variables. The relevant parameters related to COVID-19 infection will be collected .SE will be performed from 3 months to 3 years after infection. A sample size of 406 patients is required.
RESURGE: Recovery by stress echo of conventionally unfit donor good hearts.
The primary aim is to recruit hearts from donation which are currently excluded by conventional criteria as aged hearts in patients \> 55 years and ≤ 55 years with multiple risk factors. Secondary aim is to assess outcome in SE-driven transplantation compared to hearts transplanted in the same cardiac surgery centers on the basis of conventional criteria. Tertiary aim is to assess the additional prognostic value of other signs not used for decision-making. These aspects may include diastolic function, preload reserve, coronary microvascular function, and residual innervation of the intrinsic cardiac autonomic system through assessment of HRR in donor heart. In case of donor with age \>55 years o ≤ 55 years but with concomitant ≥ 3 risk factors (diabetes, hypertension, smoking, obesity, hypercholesterolemia) or history of cardiac arrest, the protocol will be applied.
SEMIR- Stress echo in ischemic mitral regurgitation
The value of SE testing as an indicator of outcome will be assessed in patients with resting moderate mitral regurgitation (effective regurgitant orifice 0.2-0.39 cm2, and regurgitant volume 30-59 ml) of ischemic origin and angiographically documented CAD, and will enter a regular clinical follow-up program with annotation of cardiovascular and non-cardiovascular endpoints. Patients undergoing CABG with or without mitral repair or PCI with or without mitral valve intervention will be separately analyzed. A sample size of 173 patients per arm (CABG or PCI) is required. The primary hypothesis is that patients with moderate mitral regurgitation worsening of ≥ 1 grade during exercise have worse outcome on medical therapy and greater benefit from valve correction. The secondary hypothesis is that patients with worse SE pre-surgery parameters will have worse prognosis independent of regurgitation severity and treatment (medical therapy or valve repair).
SEVA: Stress Echocardiography in Valvular Heart Disease
SE is recommended in valvular heart disease in patients characterized by a mismatch between resting transthoracic echocardiography findings and symptoms during exercise or activities of daily living: 1. Severe valve disease without symptoms; 2. Non-severe single- or multi-valve disease with symptoms; and 3. Symptomatic valve disease of indeterminate severity in context of low flow. The primary aim is to evaluate the feasibility of ABCDEFG-SE plus L (left atrium), P (pulmonary vascular reserve) and R (right ventricular function) in these patients. The secondary aim is to assess the correlation of each SE parameter with indices of functional severity (NYHA, cardiac natriuretic peptides, peak oxygen consumption, etc.). The tertiary aim is to assess the prognostic value of SE for prognostic stratification in the long-term. A sample size of about 217 patients per sub-group is required to evaluate the tertiary endpoint with 90% power and an alpha error of 5% .
SESPASM - SE for coronary vasospasm
The primary aim is to evaluate the feasibility and safety of hyperventilation and exercise ABCDE-SE in patients with angiographically normal coronary arteries and an intermediate-to-high pre-test probability of coronary vasospasm of epicardial arteries or microvasculature. The secondary aim is to assess the positivity rate of A and D criteria in these patients, compared to standard ECG criteria. The tertiary aim is to assess the prognostic value of the different responses of SE leading to SE-driven therapies. Only patients with strong (Class 1) indication to vasospasm testing according to the recent guidelines will be initially considered. Patients prepared for exercise testing will undergo vasospasm testing in the morning with hyperventilation. If negative or equivocal at 5 minutes after the end of hyperventilation, the patient will start exercise with the usual protocol. A sample size of 513 patients is required with a 5-year follow-up for the composite endpoint.
Related Therapeutic Areas
Sponsors
Collaborators: University Hospital, Pleven, Bulgaria, Sant'Anna School of Advanced Study, Pisa, University Hospital, Szeged, Hungary, Università Luigi Vanvitelli della Campania, Cardarelli Hospital, Naples, Italy, University Hospital, Catania, Tomsk National Research Medical Centre of the Russian, National Research Council, Institute of Clinical Physiology, Italy, University of Algarve, Portugal., Federal University of Paranà, Curitiba, Brasil, University Hospital, Padua, Italy, Presidio Ospedale San Paolo. Milano, San Luca Hospital, Lucca, DASA, San Paolo, Brasil, Malpighi Hospital, Bologna, Italy, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico, University of Bari, University of Banja Luka University Clinical Centre of the Republic of Srpska, Investigaciones Medicas, Italian Society of Echocardiography and Cardiovascular Imaging, Association for Public Health Salute Pubblica, Brindisi, Italy, IRCCS reggio emilia, Heart Center, Hospital da Cruz Vermelha, Lisbon, Mayo Clinic, Institute of Family Medicine, University of Szeged, Hungary, Elisabeth Hospital, Hódmezővásárhely, Hungary, Saint Petersburg State University Hospital, Russian Federation, University of Salerno, Antwerp University Hospital, Edegem, Belgium, Institute for Cardiovascular Diseases Dedinje, School of Medicine, Belgrade, Serbia, Bieganski Hospital, Medical University, Lodz, Poland, Ospedale San Camillo, Rome, Italy, University of Pisa, Vilnius University, Lithuania, University of Parma, University of Modena and Reggio Emilia, Universita di Verona, Hospital Sao José, Criciuma, Brasil, Clinical Hospital Zvezdara, Medical School, University of Belgrade, Serbia, Hospital Motta di Livenza, Treviso, University Center Serbia, Medical School, University of Belgrade, Serbia, University Hospital, Siena, Italy, University of A Coruna, La Coruna, Spain, Careggi Hospital, Siriraj Hospital, Ospedale per gli Infermi, Faenza, Ravenna, Italy, Hospital Sao Vicente de Paulo e Hospital de Cidade, Passo Fundo, Brasil, Dolo Hospital, Venice, Italy, Medical University of Silesia, Katowice, Poland, Centro Cardiologico Monzino, Montepulciano Hospital, Siena
Leads: Fatebenefratelli Hospital