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Stress Echo 2020 - The International Stress Echo Study (SE2020)

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ClinicalTrials.gov Identifier: NCT03049995
Recruitment Status : Recruiting
First Posted : February 10, 2017
Last Update Posted : June 2, 2017
Sponsor:
Collaborators:
Institute of Clinical Physiology, CNR, Pisa,Italy
Salerno Hospital, Italy
Monaldi Hospital, Napoli, Italy
University of Pisa, Italy
San Luca Hospital, Lucca, Italy
Careggi University Hospital, Florence, Italy
Federico II University
San Carlo Public Hospital, Potenza, Italy
Royal Brompton & Harefield NHS Foundation Trust
Ospedale dell'Angelo, Venezia-Mestre
University of Parma
Hospital Clinics, Trieste, Italy
Federal University of Rio Grande do Sul
Hospital San José, Criciuma, Brasil
Hospital San Vicente de Paulo, Passo Fundo, Brasil
University of Belgrade
University of Szeged, Hungary
Elisabeth Hospital, Hodmezovasarhely, Hungary
Sandro Pertini Hospital, Rome, Italy
Hospital Clinics, Bari, Italy
Ospedale Nottola, Siena, Italy
University of Catania, Italy
Medika Cardiocenter, Saint Petersburg, Russian Federation
Acibadem City Clinic Tokuda Hospital
Investigaciones Medicas, Buenos Aires, Argentina
Tomsk National Research Scientific Centre of Russian Academy of Sciences, Tomsk, Russian Federation
Information provided by (Responsible Party):
Fatebenefratelli Hospital

Brief Summary:
Background: Stress echocardiography (SE) has an established role in evidence-based guidelines, but recently the breadth and variety of applications has extended well beyond coronary artery disease (CAD). Purpose: To establish a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities. Methods: In a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Echocardiography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in phenotype-negative healthy relatives of inherited disease (such as hypertrophic cardiomyopathy). Expected Results:To collect about 10,000 patients over a 5-year period (2016-2020), with sample sizes ranging from 5,000 for known or suspected CAD to around 250 for hypertrophic cardiomyopathy or repaired Fallot. This data base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios. Conclusions: The study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities. The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls.

Condition or disease Intervention/treatment
Coronary Artery Disease Heart Failure Hypertrophic Cardiomyopathy Aortic Valve Disease Athletes Heart Tetralogy of Fallot Pulmonary Arterial Hypertension Procedure: Left ventricular contractile reserve SE Procedure: B-lines SE Procedure: Left ventricular outflow tract gradient SE Procedure: Diastolic function SE Procedure: Mitral regurgitation SE Procedure: Pulmonary hemodynamics SE Procedure: Coronary flow reserve SE

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 300 participants
Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration: 5 Years
Official Title: The International Stress Echo Study in Ischemic and Non-ischemic Heart Disease
Actual Study Start Date : November 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021


Group/Cohort Intervention/treatment
CHEF:Cardiac Resynchronization therapy Forecast
Patients evaluated prior to cardiac resynchronization therapy (CRT), with class I, IIa or IIb for CRT according to ESC 2016 guidelines, and with ejection fraction ≤ 35% and QRS duration ≥ 130 ms. Contractile reserve will be assessed through variations in Wall Motion Score Index and with more advanced parameters such as left ventricular elastance reserve, as the peak stress/baseline ratio of end - systolic pressure/ end-systolic volume (Left ventricular contractile reserve SE). All patients will be followed-up with resting echocardiographic examination to assess left ventricular remodelling and recovery of function. A sample size of 277 patients is required and about the same number is required to predict the response to medical therapy in patients eventually not undergoing CRT (4).
Procedure: Left ventricular contractile reserve SE
Stress protocols (either physical or pharmacological) will be performed according to recent guidelines recommendations (1,2,3). with special focus on Wall Motion Score Index.

BHEF: B-lines in HEart Failure
B- lines are a semiquantitative sign of extravascular lung water present in 1 out of 3 HF patients at rest and in 1 out of 2 during stress, and potentially useful for refining prognostic stratification and titrating diuretic therapy in these patients. We will enroll patients referred to SE with known or suspected HF, with either reduced or preserved ejection fraction. B-lines will be detected using the B-lines SE intervention. A sample size of about 2500 patients is required if the effect on mortality is evaluated.
Procedure: B-lines SE
SE will be performed with special focus on lung sonography and B-lines score (3,4).B-lines will be scored with the 28-regions antero-lateral chest assessment as previously described at baseline and immediately after stopping exercise. A simplified 8-region scan is also allowed in order to save time without loss of critical information.

SEHCA: SE in Hypertrophic Cardiomyopathy
Current guidelines recommend SE in hypertrophic cardiomyopathy (HC) solely for evaluation of left ventricular outflow tract obstruction. Large-scale registry data show that SE positivity for ischemic criteria rather than provocable gradients predict adverse outcome in HC. Low-to-intermediate risk symptomatic or asymptomatic HC patients will undergo exercise SE with assessment at each stage and during recovery of wall motion, mitral insufficiency, left ventricular outflow tract gradient (in orthostatic position)(following specific SE protocol), E/e', B-lines and, if feasible, coronary flow velocity reserve. A sample size of about 250 patients is required.
Procedure: B-lines SE
SE will be performed with special focus on lung sonography and B-lines score (3,4).B-lines will be scored with the 28-regions antero-lateral chest assessment as previously described at baseline and immediately after stopping exercise. A simplified 8-region scan is also allowed in order to save time without loss of critical information.

Procedure: Left ventricular outflow tract gradient SE
SE will be performed with special focus on left ventricular outflow tract obstruction (3,4).

SEDIA: SE in Diastolic Heart failure
Patients with suspected diastolic heart failure according to guidelines (3) will be selected (1).The diastolic assessment should be included into all exercise SE tests by measuring standard Doppler-derived mitral inflow velocity, pulsed Tissue Doppler of mitral annulus, and retrograde tricuspid gradient of tricuspid regurgitation as well as diastolic left ventricular volume index and B-lines (to provide a direct imaging of extra-vascular lung water accumulation as a direct cause of dyspnea). The test is considered positive for diastolic dysfunction when all of the following three conditions are met during exercise: average E/e' > 14 or septal E/e' ratio > 15, peak tricuspid regurgitant jet velocity >2.8 m/sec and septal e' velocity < 7 cm/s. A sample size of about 250 patients is required.
Procedure: Diastolic function SE
SE will be performed with special focus on E/e', pulmonary artery systolic pressure, B-lines and left ventricular end-diastolic volume (3,4).

SETA: SE in Transcatheter Aortic Valve implantation
Transcatheter Aortic Valve Implantation is an extraordinarily effective novel technology, and its short and long term morbidity and mortality remains significant. Patients with previous (from 6 months to 10 years) surgical or Transcatheter Aortic Valve Implantation capable of exercising will be enrolled and studied with semisupine SE. The full quantitative evaluation of mitral regurgitation and aortic stenosis will be performed. A sample size of about 100 patients is required to detect a significant stress-induced increase in mitral regurgitation severity. For the prognostic analysis 250 patients with 3 years follow-up are required.
Procedure: Mitral regurgitation SE
SE will be performed with special focus on mitral regurgitation and aortic valve gradients assessment (3,4).

SEO: SE in Outdoor in Extreme conditions
SE can also be performed outdoors, with pocket size or portable instruments, in a setting of ecological stress entirely different from standard indoor testing. The diagnostic target is the early subclinical identification of pulmonary edema. Subjects involved in extreme sporting events (competitive triathlon, marathon, apnea diving etc) or ordinary exercise in extreme environments (trekking at high altitude) will undergo lung ultrasound scan for B-lines before, soon after (within 10 minutes) and (when positive) soon after, later after (6 to 24 h) the acute extreme exercise. A sample size of 80 patients is required to detect a significant stress-induced increase in B-lines in each of the three major study subgroups: high altitude trekkers (n=100); marathon runners (n=80) and apnea divers (n=70).
Procedure: B-lines SE
SE will be performed with special focus on lung sonography and B-lines score (3,4).B-lines will be scored with the 28-regions antero-lateral chest assessment as previously described at baseline and immediately after stopping exercise. A simplified 8-region scan is also allowed in order to save time without loss of critical information.

SETOF: SE in operated Tetralogy of Fallot
Patients with repaired Tetralogy of Fallot or Fallot-like pathology (double-outlet right ventricle Fallot type, tetralogy of Fallot with pulmonary atresia), 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, New York Heart Association class I or II. Right ventricular function will be assessed at baseline and peak stress with variations (rest and peak stress) of tricuspid annular plane systolic excursion. A sample size of about 250 patients is required to detect a significant stress-induced increase in tricuspid annular plane systolic excursion.
Procedure: Pulmonary hemodynamics SE
SE will be performed with special focus on pulmonary artery systolic pressure and pulmonary artery hemodynamics.

DOSPAH: Doppler SE in Pulmonary Arterial Hypertension
Patients at risk, borderline, or early established pulmonary hypertension capable of exercising will be recruited by regional reference centers, a physical stress will be performed and the hemodynamic assessment will include the assessment of pulmonary hemodynamics. The primary positivity criteria are the increase in systolic pulmonary artery pressure (> 40 mmHg) and the flow-adjusted variation in pulmonary vascular resistances. A sample size of about 250 patients is required to detect a significant stress-induced hemodynamic changes with a 3 -year follow-up.
Procedure: Pulmonary hemodynamics SE
SE will be performed with special focus on pulmonary artery systolic pressure and pulmonary artery hemodynamics.

DITSE: Diagnosis of CAD by imaging SE
A clear step-up in diagnostic sensitivity (with a modest loss in specificity) and risk stratification capability is obtained with assessment of coronary flow velocity reserve in the left anterior descending coronary artery,left ventricular contractile reserve through changes in left ventricular elastance, and B-lines. "Allcomers" referred to the SE lab with suspected CAD will be evaluated with standard regional wall motion analysis and also - whenever feasible - with left ventricular coronary flow reserve and left ventricular elastance reserve and - when possible- B-lines ("quadruple imaging").A sample size of about 5,000 patients will be required.
Procedure: Left ventricular contractile reserve SE
Stress protocols (either physical or pharmacological) will be performed according to recent guidelines recommendations (1,2,3). with special focus on Wall Motion Score Index.

Procedure: B-lines SE
SE will be performed with special focus on lung sonography and B-lines score (3,4).B-lines will be scored with the 28-regions antero-lateral chest assessment as previously described at baseline and immediately after stopping exercise. A simplified 8-region scan is also allowed in order to save time without loss of critical information.

Procedure: Coronary flow reserve SE
SE will be performed with special focus on regional wall motion + coronary artery flow velocity reserve.

GENES: Genetic Stress echocardiography
The identification of phenotype-negative and genotype positive carriers of pathologic mutations is an important, still elusive, target. We will initially select 75 patients (25 for each disease) with documented disease and mutant gene. We will enroll 250 first-degree relatives of the initially considered probands, with normal findings at rest and age range preferentially between 10 and 21 years. SE testing will be tailored on the specific question: hypertrophic cardiomyopathy as in protocol 3 (left ventricular outflow tract gradient); pulmonary hypertension as in protocol 8 (pulmonary vascular resistances);dilated cardiomyopathy as in protocol 1 (left ventricular elastance). A sample size of about 80 patients for each disease will be required.
Procedure: Left ventricular contractile reserve SE
Stress protocols (either physical or pharmacological) will be performed according to recent guidelines recommendations (1,2,3). with special focus on Wall Motion Score Index.

Procedure: Left ventricular outflow tract gradient SE
SE will be performed with special focus on left ventricular outflow tract obstruction (3,4).

Procedure: Pulmonary hemodynamics SE
SE will be performed with special focus on pulmonary artery systolic pressure and pulmonary artery hemodynamics.




Primary Outcome Measures :
  1. all cause death [ Time Frame: 5 years ]
    Death from any cause occurring between 5 years after the time of SE enrollment

  2. cardiac death [ Time Frame: 5 years ]
    Death from cardiac cause occurring between 5 years after the time of SE enrollment

  3. transplantation [ Time Frame: 5 years ]
    Cardiac transplantation occurring between 5 years after the time of SE enrollment


Secondary Outcome Measures :
  1. clinical (NYHA class IV) or functional (EF 30>10%) [ Time Frame: 5 years ]
    signs and symptoms consistent with heart failure which required hospitalization between 5 years after the time of SE enrollment


Biospecimen Retention:   Samples With DNA
Blood and saliva will be collected in patients of "GENES"protocol.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
  1. Heart Failure patients candidates for cardiac resynchronization therapy.
  2. Patients with known or suspected HF.
  3. Hypertrophic cardiomyopathy.
  4. HF with preserved ejection fraction.
  5. Patients with aortic valve replacement.
  6. Healthy volunteers involved in extreme sporting events (competitive triathlon, marathon, apnea diving etc).
  7. Tetralogy of Fallot operated patients.
  8. At risk borderline, or early established pulmonary hypertension.
  9. Known or suspected CAD.
  10. First degree relatives with familial dilated cardiomyopathy, pulmonary hypertension or hypertrophic cardiomyopathy.
Criteria

Inclusion criteria shared by all projects are:

  • age < 85 years and > 18 years (except for project 7 regarding repaired tetralogy of Fallot and project 10 regarding healthy relatives of patients with familial disease, in which children > 10 years can enter the study after parental consent);
  • technically acceptable acoustic window at rest (with at least 14 segments well visualized in at least one projection).

Exclusion criteria shared by all projects are:

  • presence of prognosis-limiting comorbidities, such as advanced cancer, reducing life expectancy to < 1 year;
  • pregnancy/lactation;
  • unwillingness to give informed consent and to enter a regular follow-up program.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03049995


Contacts
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Contact: Quirino Ciampi, MD qciampi@gmail.com

Locations
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Italy
Fatebenefratelli Hospital Recruiting
Benevento, Italy
Contact: Quirino Ciampi, MD         
Sponsors and Collaborators
Fatebenefratelli Hospital
Institute of Clinical Physiology, CNR, Pisa,Italy
Salerno Hospital, Italy
Monaldi Hospital, Napoli, Italy
University of Pisa, Italy
San Luca Hospital, Lucca, Italy
Careggi University Hospital, Florence, Italy
Federico II University
San Carlo Public Hospital, Potenza, Italy
Royal Brompton & Harefield NHS Foundation Trust
Ospedale dell'Angelo, Venezia-Mestre
University of Parma
Hospital Clinics, Trieste, Italy
Federal University of Rio Grande do Sul
Hospital San José, Criciuma, Brasil
Hospital San Vicente de Paulo, Passo Fundo, Brasil
University of Belgrade
University of Szeged, Hungary
Elisabeth Hospital, Hodmezovasarhely, Hungary
Sandro Pertini Hospital, Rome, Italy
Hospital Clinics, Bari, Italy
Ospedale Nottola, Siena, Italy
University of Catania, Italy
Medika Cardiocenter, Saint Petersburg, Russian Federation
Acibadem City Clinic Tokuda Hospital
Investigaciones Medicas, Buenos Aires, Argentina
Tomsk National Research Scientific Centre of Russian Academy of Sciences, Tomsk, Russian Federation
Investigators
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Principal Investigator: Quirino Ciampi, MD Fatebenefratelli Hospital
Additional Information:

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Fatebenefratelli Hospital
ClinicalTrials.gov Identifier: NCT03049995    
Other Study ID Numbers: FBF001
First Posted: February 10, 2017    Key Record Dates
Last Update Posted: June 2, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Fatebenefratelli Hospital:
effectiveness; imaging; prognosis; stress echocardiography
Additional relevant MeSH terms:
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Hypertension
Coronary Artery Disease
Cardiomyopathies
Cardiomyopathy, Hypertrophic
Tetralogy of Fallot
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Coronary Disease
Myocardial Ischemia
Arteriosclerosis
Arterial Occlusive Diseases
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Congenital Abnormalities