Microvascular Dysfunction Assessment to Predict Left Ventricular Reverse Remodeling

Heart Failure Clinical Trial

— MICROREV  

Official title:

Microvascular Dysfunction Assessment to Predict Left Ventricular Reverse Remodeling in Idiopathic Dilated Cardiomyopathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06356727
• Other study ID #: 121CET-MICROREV-DCM
• Status: Recruiting
• Phase: N/A
• Start date: January 3, 2024
• Est. completion date: January 31, 2030

Study information

• Verified date: April 2024
• Source: Azienda Ospedaliera Universitaria Integrata Verona
• Contact: Natascia Antonioli
• Phone: 0039 0458122320
• Email: studi.clinici.cardiologia[@]aovr.veneto.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a prospective, multicentric, single-arm explorative clinical study in patients presenting with heart failure and idiopathic dilated cardiomyopathy with LVEF ≤ 40%. Patients identified as eligible for the protocol will be asked for written informed consent to participate in the study.

After appropriate treatment of the acute heart failure phase, participants will undergo coronary angiography to rule out obstructive coronary disease.

Fractional flow reserve (FFR) will be assessed as per standard clinical practice and a value ≤ 0.80 will be considered abnormal. Microvascular assessment will be performed using the same pressure/thermodilution guidewire used for FFR assessment with the derivation of coronary flow reserve (CFR), index of microcirculatory resistance (IMR) and the microvascular resistance reserve (MRR).

Steady-state hyperemia will be obtained using an intravenous adenosine infusion or intracoronary papaverine as per routine clinical practice.

The primary endpoint will be assessed based on the variation of echocardiographic indices from the baseline to 12-month follow up. Transthoracic echocardiography will be performed to confirm the diagnosis and obtain information about adverse cardiac remodeling and after 12 months of optimal medical therapy to evaluate reverse remodeling.

Patients will be clinically managed by a dedicated heart failure team to optimize medical therapy and organize the follow-up.

Patients enrolled in the study will be clinically followed for a period of 5 years to monitor the clinical status and report major adverse cardiac events.

During the study period participants may undergo multimodality diagnostic tests according to the recent international guidelines. Data from these tests will be collected if the test will be performed per clinical practice:

1. 3-leads ECG telemetry monitoring (or 24 hours Holter ECG) to detect or quantify atrial and/or ventricular arrhythmias during the hospitalization.

2. N-terminal pro-B-type natriuretic peptide (NT - proBNP).

3. Cardiopulmonary exercise testing (CPET) to assess functional capacity.

4. Contrast enhanced cardiac magnetic resonance. CMR assessment may be repeated at 12 months follow-up.

5. Genetic counseling and genetic testing, performed by an appropriately trained healthcare professional is recommended in patients with idiopathic DCM by the latest international guidelines to enable diagnosis, prognostication, therapeutic stratification.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 190
• Est. completion date: January 31, 2030
• Est. primary completion date: January 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Heart Failure
• Idiopathic Dilated Cardiomyopathy
• Left Ventricular Dysfunction
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

Intervention

Diagnostic Test:
• Thermodilution based assessment of coronary microcirculation
Coronary microvascular assessment with the derivation of CFR, IMR and MRR will be performed using a standard pressure/thermodilution guidewire.

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Universitaria di Ferrara	Ferrara
Italy	Cardiothoracic and Vascular Department (DICATOV) IRCCS, Ospedale Policlinico San Martino	Genova
Italy	Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) dell'Ospedale San Raffaele	Milan
Italy	Ospedale Galeazzi di Sant'Ambrogio IRCCS	Milan
Italy	University of Naples Federico II	Naples
Italy	Fondazione Policlinico Universitario A. Gemelli IRCCS	Roma
Italy	Azienda Ospedaliero-Universitaria Sant'Andrea	Rome
Italy	Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino	Torino
Italy	Azienda Ospedaliera Universitaria di Verona	Verona

Sponsors (2)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria Integrata Verona	Abbott Medical Devices

Country where clinical trial is conducted

Italy, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Eur Heart J. 2021 Oct 14;: — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Adverse clinical events	Composite of cardiovascular death, new hospitalization for HF, ICD implantation, heart transplantation or ventricular mechanical assistance implantation during follow-up in patients with and without coronary microvascular dysfunction	Up to 5 years
Secondary	Rate of LVRR at cardiac magnetic resonance	LVRR, defined as LVEF increase = 10% and LVEDDi decrease = 10%, in patients who will undergo CMR at baseline and at 12 months follow up.	After 12 months of guidelines directed OMT
Secondary	Changes in functional capacity at cardiopulmonary exercise test	Variations of VO2 max at CPET after 12 months of guidelines-defined OMT	After 12 months of guidelines-defined OMT
Secondary	Prevalence of different CMD endotypes and their correlation with the severity of adverse cardiac remodeling.	CMD endotypes (defined as IMR >25 units and/or CFR <2)	At baseline
Secondary	Left ventricle adverse cardiac remodeling at cardiovascular magnetic resonance.	Measures of LV adverse remodeling at CMR	At baseline