Heart Failure, Idiopathic Dilated Cardiomyopathy, Left Ventricular Dysfunction
Conditions
Keywords
coronary microvascular dysfunction, heart failure, left ventricular reverse remodeling, optimal medical therapy
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.
Interventions
DIAGNOSTIC_TESTThermodilution 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.
Sponsors
Abbott Medical Devices
Azienda Ospedaliera Universitaria Integrata Verona
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Left ventricular reverse remodeling (LVRR) | After 12 months of guidelines directed optimal medical therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse clinical events | Up to 5 years | 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 |
| Rate of LVRR at cardiac magnetic resonance | After 12 months of guidelines directed OMT | LVRR, defined as LVEF increase ≥ 10% and LVEDDi decrease ≥ 10%, in patients who will undergo CMR at baseline and at 12 months follow up. |
| Changes in functional capacity at cardiopulmonary exercise test | After 12 months of guidelines-defined OMT | Variations of VO2 max at CPET after 12 months of guidelines-defined OMT |
| Prevalence of different CMD endotypes and their correlation with the severity of adverse cardiac remodeling. | At baseline | CMD endotypes (defined as IMR \>25 units and/or CFR \<2) |
| Left ventricle adverse cardiac remodeling at cardiovascular magnetic resonance. | At baseline | Measures of LV adverse remodeling at CMR |
Countries
Italy
Contacts
Primary ContactNatascia Antonioli
Outcome results
None listed