Unmasking the Prevalence of AC in an Unselected Echocardiographic Population

Amyloid Cardiomyopathy Clinical Trial

— AC-TIVE  

Official title:

A National Survey of Prevalence and Accuracy of Echocardiographic Red Flags of Amyloid Cardiomyopathy in Consecutive Patients Undergoing Routine Echocardiography.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04738266
• Other study ID #: 199_2019
• Status: Active, not recruiting
• Start date: November 20, 2020
• Est. completion date: July 25, 2021

Study information

• Verified date: February 2021
• Source: University of Trieste
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

This study will investigate the prevalence of echocardiographic red-flags of amyloid cardiomyopathy (AC) in patients undergoing clinically-indicated echocardiography (observational phase) and the prevalence of AC among AC-suggestive echocardiograms (interventional phase).

Description:

Prospective multicenter Italian survey consisting of two phases: observational (echocardiographic screening for amyloid cardiomyopathy among patients ≥ 55 years undergoing clinically-indicated echocardiography) and interventional (specific clinical and instrumental work-up to detect the prevalence of amyloid cardiomyopathy among amyloid cardiomyopathy-suggestive echocardiograms).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 381
• Est. completion date: July 25, 2021
• Est. primary completion date: January 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 100 Years

Eligibility

Inclusion Criteria:

All the following:

• Interventricular septum thickness = 13 mm in men and = 12 mm in women;
• Left ventricular ejection fraction = 50%;
• Indexed end-diastolic left ventricular volume = 85 mL/m2. AND

At least one of the following criteria:

• "Granular sparkling" appearance of the myocardium defined granular texture with uniform increased brightness of echo-reflections;
• Pericardial effusion regardless of severity;
• Increased interatrial septum thickness (> 5 mm);
• Restrictive filling pattern (Dec. Time E wave <120 ms or Dec. Time E wave =150 ms e E/A ratio =2) or increased ventricular filling pressures (E/E'15);
• Speckle tracking derived global longitudinal strain with apical sparing pattern;
• Increased thickness (> 5 mm) of mitral and tricuspid valve leaflets.

Exclusion Criteria:

• Patients aged < 55 years or > 100 years
• Echocardiography performed due to known or suspected amyloid cardiomyopathy;
• Echocardiography performed due to known hypertrophic cardiomyopathy or phenocopies;
• Refuse to sign the informed consent to the study

Related Conditions & MeSH terms

• Amyloid Cardiomyopathy
• Amyloidosis
• Cardiomyopathies

Intervention

Diagnostic Test:
• Amyloid Cardiomyopathy
Echocardiographic red flags of Amyloid Cardiomyopathy to guide the suspicion of disease and to proceed with second level diagnostic work up including cardiac scintigraphy with bone tracers and search of monoclonal component in serum and urine

Locations

Country	Name	City	State
Italy	Cardiology Unit, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro	Bari
Italy	Cardiovascular Department, Policlinico Sant'Orsola	Bologna
Italy	Cardiology, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health - University of Brescia	Brescia
Italy	Cardiology Unit, Azienda Ospedaliero Universitaria di Ferrara	Ferrara
Italy	Cardiomyopathy Unit, Careggi University Hospital	Firenze
Italy	Cardiovascular Unit, Department of Internal Medicine, University of Genova	Genova
Italy	Department of Cardiology, University of Messina	Messina
Italy	Department of Cardiovascular, Neural and Metabolic Sciences - Istituto Auxologico Italiano	Milano
Italy	Department of medicine and surgery, University Milano-Bicocca	Milano
Italy	Department of Translational Medical Sciences, Inherited and Rare Heart Disease, Vanvitelli Cardiology, University of Campania Luigi Vanvitelli	Napoli
Italy	Emergency Department and Amyloid Research and Treatment Center, IRCCS Policlinico San Matteo Foundation, Department of Internal Medicine, University of Pavia	Pavia	Milano
Italy	Istituto di Scienze della Vita, Scuola Superiore Sant'Anna	Pisa
Italy	Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University	Roma
Italy	Division of Cardiology, University of Siena	Siena
Italy	University Cardiology A.O.U., Città della Salute e della Scienza di Torino	Torino
Italy	Centre for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI)	Trieste

Sponsors (2)

Lead Sponsor	Collaborator
University of Trieste	Pfizer

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Boldrini M, Cappelli F, Chacko L, Restrepo-Cordoba MA, Lopez-Sainz A, Giannoni A, Aimo A, Baggiano A, Martinez-Naharro A, Whelan C, Quarta C, Passino C, Castiglione V, Chubuchnyi V, Spini V, Taddei C, Vergaro G, Petrie A, Ruiz-Guerrero L, Moñivas V, Mingo-Santos S, Mirelis JG, Dominguez F, Gonzalez-Lopez E, Perlini S, Pontone G, Gillmore J, Hawkins PN, Garcia-Pavia P, Emdin M, Fontana M. Multiparametric Echocardiography Scores for the Diagnosis of Cardiac Amyloidosis. JACC Cardiovasc Imaging. 2020 Apr;13(4):909-920. doi: 10.1016/j.jcmg.2019.10.011. Epub 2019 Dec 18. — View Citation

Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, Wechalekar AD, Berk JL, Quarta CC, Grogan M, Lachmann HJ, Bokhari S, Castano A, Dorbala S, Johnson GB, Glaudemans AW, Rezk T, Fontana M, Palladini G, Milani P, Guidalotti PL, Flatman K, Lane T, Vonberg FW, Whelan CJ, Moon JC, Ruberg FL, Miller EJ, Hutt DF, Hazenberg BP, Rapezzi C, Hawkins PN. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016 Jun 14;133(24):2404-12. doi: 10.1161/CIRCULATIONAHA.116.021612. Epub 2016 Apr 22. — View Citation

Maurer MS, Bokhari S, Damy T, Dorbala S, Drachman BM, Fontana M, Grogan M, Kristen AV, Lousada I, Nativi-Nicolau J, Cristina Quarta C, Rapezzi C, Ruberg FL, Witteles R, Merlini G. Expert Consensus Recommendations for the Suspicion and Diagnosis of Transthyretin Cardiac Amyloidosis. Circ Heart Fail. 2019 Sep;12(9):e006075. doi: 10.1161/CIRCHEARTFAILURE.119.006075. Epub 2019 Sep 4. Review. — View Citation

Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing Common Questions Encountered in the Diagnosis and Management of Cardiac Amyloidosis. Circulation. 2017 Apr 4;135(14):1357-1377. doi: 10.1161/CIRCULATIONAHA.116.024438. Review. — View Citation

Maurer MS, Hanna M, Grogan M, Dispenzieri A, Witteles R, Drachman B, Judge DP, Lenihan DJ, Gottlieb SS, Shah SJ, Steidley DE, Ventura H, Murali S, Silver MA, Jacoby D, Fedson S, Hummel SL, Kristen AV, Damy T, Planté-Bordeneuve V, Coelho T, Mundayat R, Suhr OB, Waddington Cruz M, Rapezzi C; THAOS Investigators. Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016 Jul 12;68(2):161-72. doi: 10.1016/j.jacc.2016.03.596. — View Citation

Porcari A, Merlo M, Rapezzi C, Sinagra G. Transthyretin amyloid cardiomyopathy: An uncharted territory awaiting discovery. Eur J Intern Med. 2020 Dec;82:7-15. doi: 10.1016/j.ejim.2020.09.025. Epub 2020 Oct 5. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The prevalence of Amyloid Cardiomyopathy	The prevalence of Amyloid Cardiomyopathy in unselected echocardiographic population of patients aged > 55 years	3 months
Primary	The prevalence of echocardiographic red flags of Amyloid Cardiomyopathy	The prevalence of echocardiographic red flags of Amyloid Cardiomyopathy in unselected echocardiographic population of patients aged > 55 years	6 months
Primary	The diagnostic accuracy of echocardiographic red flags of Amyloid Cardiomyopathy	At the end of phase 2 of this study, patients with Amyloid Cardiomyopathy will be diagnosed, thus allowing to measure the diagnostic accuracy of the following echocardiographic red flags of Amyloid Cardiomyopathy: Restrictive filling pattern (E wave deceleration time <120 ms or =150 ms in presence of E/A =2) and/or E/E'=15; "Granular sparkling" appearance of the myocardium; Pericardial effusion of any entity; Interatrial septum thickness >0.5 cm measured in subcostal or four-chamber view; Thickening of the atrio-ventricular (AV) valves (leaflets thickness >0.5 cm); Left ventricular "apical sparing" pattern at speckle-tracking echocardiography.	6 months
Secondary	Multiparametric echocardiographic score	Multiparametric echocardiographic score to predict the presence of Amyloid Cardiomyopathy	6 months