Clinical trial NCT06356727: Microvascular Dysfunction Assessment to Predict Left Ventricular Reverse Remodeling
Official title: Microvascular Dysfunction Assessment to Predict Left Ventricular Reverse Remodeling in Idiopathic Dilated Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Left Ventricular Dysfunction
Idiopathic Dilated Cardiomyopathy
Keywords: coronary microvascular dysfunction
heart failure
left ventricular reverse remodeling
optimal medical therapy
Lead sponsor: Azienda Ospedaliera Universitaria Integrata Verona
Sponsor class: OTHER
Collaborators: name: Abbott Medical Devices
First posted: 2024-04-10
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: SUPPORTIVE_CARE

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.

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.

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

Primary outcomes:
measure: Rate of Left ventricular reverse remodeling (LVRR)
timeFrame: After 12 months of guidelines directed optimal medical therapy
Secondary outcomes:
measure: Adverse clinical events
timeFrame: Up to 5 years
measure: Rate of LVRR at cardiac magnetic resonance
timeFrame: After 12 months of guidelines directed OMT
measure: Changes in functional capacity at cardiopulmonary exercise test
timeFrame: After 12 months of guidelines-defined OMT
measure: Prevalence of different CMD endotypes and their correlation with the severity of adverse cardiac remodeling.
timeFrame: At baseline
measure: Left ventricle adverse cardiac remodeling at cardiovascular magnetic resonance.
timeFrame: At baseline
Other outcomes:
Locations:
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Universitaria di Ferrara
city: Genova
country: Italy
facility: Cardiothoracic and Vascular Department (DICATOV) IRCCS, Ospedale Policlinico San Martino
city: Milan
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) dell'Ospedale San Raffaele
city: Milan
country: Italy
facility: Ospedale Galeazzi di Sant'Ambrogio IRCCS
city: Naples
country: Italy
facility: University of Naples Federico II
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS
city: Rome
country: Italy
facility: Azienda Ospedaliero-Universitaria Sant'Andrea
city: Torino
country: Italy
facility: Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria di Verona
Study officials:
affiliation: Azienda Ospedaliera Universitaria di Verona
name: Roberto Scarsini, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.
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.
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.