Microvascular Dysfunction Assessment to Predict Left Ventricular Reverse Remodeling

NCT06356727 | Recruiting

• 1 other identifier: 121CET-MICROREV-DCM
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 9

Brief Summary

Patients presenting with idiopathic dilated cardiomyopathy and left ventricle dysfunction (LVEF \<40%), naive of anti-remodeling cardiac medical therapy, will undergo invasive coronary microvascular assessment based on thermodilution. The primary endpoint, namely the left ventricle reverse remodeling, will be assessed after 12 months of optimal medical therapy based on transthoracic echocardiography. The primary endpoint will be evaluated by an independent central core lab. Patients enrolled in the study will be followed for a period of 5 years to monitor their clinical status. During the study period participants may undergo multimodality diagnostic tests including ECG telemetry monitoring, cardiopulmonary exercise testing, cardiovascular cardiac magnetic resonance.

Conditions

Heart Failure; Left Ventricular Dysfunction; Idiopathic Dilated Cardiomyopathy

Keywords

coronary microvascular dysfunction; heart failure; left ventricular reverse remodeling; optimal medical therapy

Outcome Measures

Primary Outcomes (1)

• Rate of Left ventricular reverse remodeling (LVRR)

  LVRR, defined as LVEF increase ≥ 10% and LVEDDi decrease ≥ 10%, will be assessed with transthoracic echocardiography and analyzed off-line by an independent central corelab.

  After 12 months of guidelines directed optimal medical therapy

Secondary Outcomes (5)

• Adverse clinical events

  Up to 5 years

• Rate of LVRR at cardiac magnetic resonance

  After 12 months of guidelines directed OMT

• Changes in functional capacity at cardiopulmonary exercise test

  After 12 months of guidelines-defined OMT

• Prevalence of different CMD endotypes and their correlation with the severity of adverse cardiac remodeling.

  At baseline

• Left ventricle adverse cardiac remodeling at cardiovascular magnetic resonance.

  At baseline

Study Arms (1)

Microvascular assessment

EXPERIMENTAL

Coronary microvascular assessment

Diagnostic Test: Thermodilution based assessment of coronary microcirculation

Interventions

Thermodilution based assessment of coronary microcirculation DIAGNOSTIC_TEST

Coronary microvascular assessment with the derivation of CFR, IMR and MRR will be performed using a standard pressure/thermodilution guidewire.

Microvascular assessment

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged \>18 years
• First diagnosis of idiopathic DCM (defined according to the most recent ESC Guidelines) with LVEF ≤ 40% and clinical indication to diagnostic coronary angiography
• Willing and able to give informed consent for participation in the study

You may not qualify if:

• Obstructive CAD (defined as angiographically intermediate disease \[50%-70%\] with impaired FFR or as angiographically severe disease \[\>70%\] in 1 or more epicardial vessels)
• History of previous myocardial infarction, percutaneous revascularization or coronary-aortic bypass graft (CABG) surgery
• Valvular heart disease (rheumatic heart disease, severe aortic stenosis, severe aortic regurgitation, severe primary mitral regurgitation)
• Infective endocarditis
• Congenital heart disease
• Peripartum cardiomyopathy
• Acute myocarditis (detected by endomyocardial biopsy - histological criteria - or by CMR - Lake Louis criteria) and pericarditis
• Persistent tachyarrhythmias (documented persistent high-rate supraventricular arrhythmias)
• Excessive alcohol intake (\>80 g/die for at least five years)
• History of chemotherapy (anthracycline therapy, cumulative dosages \>250 mg/m2)
• History of uncontrolled arterial hypertension (blood pressure \>160/100 mmHg)
• Stage IV and V of chronic kidney disease (eGFR \< 30 ml/min, estimated through CKD - EPI Creatinine Equation)
• Allergy or other contraindication to iodinated contrast and/or adenosine
• Chronic resting O2 saturation \<85%
• Pregnancy or suspected pregnancy

Sponsors & Collaborators

• Azienda Ospedaliera Universitaria Integrata Verona: lead
• Abbott Medical Devices: collaborator

Study Sites (9)

Azienda Ospedaliera Universitaria di Ferrara

Ferrara, Italy

NOT YET RECRUITING

Cardiothoracic and Vascular Department (DICATOV) IRCCS, Ospedale Policlinico San Martino

Genova, Italy

NOT YET RECRUITING

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) dell'Ospedale San Raffaele

Milan, Italy

NOT YET RECRUITING

Ospedale Galeazzi di Sant'Ambrogio IRCCS

Milan, Italy

NOT YET RECRUITING

University of Naples Federico II

Naples, Italy

NOT YET RECRUITING

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Sant'Andrea

Rome, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino

Torino, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria di Verona

Verona, 37126, Italy

RECRUITING

Related Publications (6)

• Arbelo E, Protonotarios A, Gimeno JR, Arbustini E, Barriales-Villa R, Basso C, Bezzina CR, Biagini E, Blom NA, de Boer RA, De Winter T, Elliott PM, Flather M, Garcia-Pavia P, Haugaa KH, Ingles J, Jurcut RO, Klaassen S, Limongelli G, Loeys B, Mogensen J, Olivotto I, Pantazis A, Sharma S, Van Tintelen JP, Ware JS, Kaski JP; ESC Scientific Document Group. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J. 2023 Oct 1;44(37):3503-3626. doi: 10.1093/eurheartj/ehad194. No abstract available.

  PMID: 37622657 BACKGROUND

• McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.

  PMID: 34447992 BACKGROUND

• Merlo M, Pyxaras SA, Pinamonti B, Barbati G, Di Lenarda A, Sinagra G. Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment. J Am Coll Cardiol. 2011 Mar 29;57(13):1468-76. doi: 10.1016/j.jacc.2010.11.030.

  PMID: 21435516 BACKGROUND

• Rosano GMC, Moura B, Metra M, Bohm M, Bauersachs J, Ben Gal T, Adamopoulos S, Abdelhamid M, Bistola V, Celutkiene J, Chioncel O, Farmakis D, Ferrari R, Filippatos G, Hill L, Jankowska EA, Jaarsma T, Jhund P, Lainscak M, Lopatin Y, Lund LH, Milicic D, Mullens W, Pinto F, Ponikowski P, Savarese G, Thum T, Volterrani M, Anker SD, Seferovic PM, Coats AJS. Patient profiling in heart failure for tailoring medical therapy. A consensus document of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2021 Jun;23(6):872-881. doi: 10.1002/ejhf.2206. Epub 2021 May 20.

  PMID: 33932268 BACKGROUND

• Del Buono MG, Montone RA, Camilli M, Carbone S, Narula J, Lavie CJ, Niccoli G, Crea F. Coronary Microvascular Dysfunction Across the Spectrum of Cardiovascular Diseases: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021 Sep 28;78(13):1352-1371. doi: 10.1016/j.jacc.2021.07.042.

  PMID: 34556322 BACKGROUND

• Gulati A, Ismail TF, Ali A, Hsu LY, Goncalves C, Ismail NA, Krishnathasan K, Davendralingam N, Ferreira P, Halliday BP, Jones DA, Wage R, Newsome S, Gatehouse P, Firmin D, Jabbour A, Assomull RG, Mathur A, Pennell DJ, Arai AE, Prasad SK. Microvascular Dysfunction in Dilated Cardiomyopathy: A Quantitative Stress Perfusion Cardiovascular Magnetic Resonance Study. JACC Cardiovasc Imaging. 2019 Aug;12(8 Pt 2):1699-1708. doi: 10.1016/j.jcmg.2018.10.032. Epub 2019 Jan 16.

  PMID: 30660522 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Ventricular Dysfunction, Left; Cardiomyopathy, Dilated

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction; Cardiomegaly; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Roberto Scarsini, MD PhD

  Azienda Ospedaliera Universitaria di Verona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natascia Antonioli

CONTACT

0039 0458122320; studi.clinici.cardiologia@aovr.veneto.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Prospective multicenter single-arm experimental study. The study aims to perform a functional study of the coronary microcirculation with pressure guides, in patients with new diagnoses of dilated cardiomyopathy and clinical indication for coronary angiography. Following this, a multiparametric imaging study with transthoracic echo cardiography will be performed. 12 months after the optimization of medical therapy, the patient will receive a clinical, laboratory and instrumental re-evaluation of transthoracic cardiac color Doppler. The primary endpoint is the recovery of left ventricular function on cardiac imaging. Follow up will continue up to 5 years from enrollment through telephone contacts, outpatient visits and review of clinical data.

Study Record Dates

• First Submitted: March 30, 2024
• First Posted: April 10, 2024
• Study Start: January 3, 2024
• Primary Completion: January 31, 2026
• Study Completion (Estimated): January 31, 2030
• Last Updated: April 10, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The present study is powered for assessing left ventricular reverse remodeling in patients with and without coronary microvascular dysfunction. However, the study is not powered for clinical adverse events. In order to obtain compelling evidence on this latter endpoint, the data of the present study will be merged with those of clinical studies sharing the same inclusion and exclusion criteria and study interventions. Data will be available for individual patient level analysis in order to merge our data with other studies sharing inclusion and exclusion criteria. Data will be available after the completion of the primary endpoint.
• Access Criteria: Direct request to study Principal Investigator.

Locations

IT (9)