Microvascular Dysfunction Assessment to Predict Left Ventricular Reverse Remodeling

Official title

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

Overview

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.

Detailed 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.

Interventions

• 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.

Primary outcome measures

• Rate of Left ventricular reverse remodeling (LVRR) [Time frame: After 12 months of guidelines directed optimal medical therapy]

Secondary outcome measures (5)

• Adverse clinical events [Time frame: Up to 5 years]
• Rate of LVRR at cardiac magnetic resonance [Time frame: After 12 months of guidelines directed OMT]
• Changes in functional capacity at cardiopulmonary exercise test [Time frame: After 12 months of guidelines-defined OMT]
• Prevalence of different CMD endotypes and their correlation with the severity of adverse cardiac remodeling. [Time frame: At baseline]
• Left ventricle adverse cardiac remodeling at cardiovascular magnetic resonance. [Time frame: At baseline]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Supportive care

Study locations

Italy · 9 centers

• Azienda Ospedaliera Universitaria di Ferrara — Ferrara
• Cardiothoracic and Vascular Department (DICATOV) IRCCS, Ospedale Policlinico San Martino — Genova
• Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) dell'Ospedale San Raffaele — Milan
• Ospedale Galeazzi di Sant'Ambrogio IRCCS — Milan
• University of Naples Federico II — Naples
• Fondazione Policlinico Universitario A. Gemelli IRCCS — Roma
• Azienda Ospedaliero-Universitaria Sant'Andrea — Rome
• Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino — Torino
• … and 1 more center

Publications

• 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 car PMID 37622657
• 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 Gro PMID 34447992
• 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
• 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 tailori PMID 33932268
• 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
• 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 PMID 30660522

Identifiers

NCT: NCT06356727 · 121CET-MICROREV-DCM

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗