Characterization of Myocardial Interstitial Fibrosis and Cardiomyocyte Hypertrophy by Cardiac MRI in Heart Failure

Heart Failure Clinical Trial

Official title:

Characterization of Myocardial Interstitial Fibrosis and Cardiomyocyte Hypertrophy by Cardiac MRI In Heart Failure: Implication on Early Remodeling and on the Transition to Heart Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03084679
• Other study ID #: HF-CMR-53967215800005404
• Secondary ID: FAPESP 2015/1540
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2017
• Est. completion date: July 2020

Study information

• Verified date: June 2019
• Source: University of Campinas, Brazil
• Contact: OTAVIO R COELHO-FILHO, MD, MPH, PhD
• Phone: 996038484
• Email: tavicocoelho[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators hypothesised that novel MRI metrics derived from myocardium post-gadolinium T1 mapping analysis will improve the current knowledge about the role interstitial fibrosis and cardiomyocyte hypertrophy in the development of left ventricular (LV) remodelling and clinical Heart Failure (HF). The investigators believe that these recently described variables will be associated with prognostically important indices in HF development.

Description:

Cardiac hypertrophy is one of the earliest manifestations of myocardial disease, representing a modifiable, prognostic response to hemodynamic stimuli across physiologic (e.g., exercise) and pathologic states (e.g., hypertension, aortic stenosis). The extent of myocardial hypertrophy is determined by a combination of cardiomyocyte size and extracellular volume (ECV) expansion/interstitial fibrosis: while physiologic (exercise-induced) hypertrophy reflects mostly reversible cardiomyocyte hypertrophy, pathologic hypertrophy (e.g., in heart failure) is a combination of both interstitial fibrosis (potentially irreversible) and cardiomyocyte hypertrophy (reversible). Current methods to delineate the potential for LV reverse remodeling (e.g., natriuretic peptides and echocardiographic or clinical markers) detect primarily advanced disease, missing a critical opportunity to intervene and follow patients at an early disease phase where myocardial pathology may be reversible. Therefore, establishing novel, quantitative metrics of myocardial tissue phenotype that define a transition from hypertrophy to fibrosis, and then to irreversible LV remodeling/dysfunction may facilitate targeting therapies at a modifiable stage of disease in HF. The investigator's group has recently extended cardiac T1 mapping MRI techniques to quantify the intracellular lifetime of water (τic) serially as an index of cardiomyocyte diameter, validating this technique histologically in mouse models of pressure overload.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: July 2020
• Est. primary completion date: June 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age> 18 years

• Functional limitation (New York Heart Association Class II or worse)

• No contraindication to exercise (American College of Cardiology / American Heart Association criteria)

• Eligibility to take MRI (absence of metallic devices, and glomerular filtration rate > 40ml / min / 1.73m2, etc.)

• Prior diagnosis of Heart Failure (by the Framingham criterion)

• Therapy with diuretic and euvolemia state (evaluated by cardiologist and cardiopulmonary exercise testing)

• Transthoracic echocardiogram

Exclusion Criteria:

• Severe ischemia in any stress test

• Hypertrophic cardiomyopathy or any infiltrative heart disease

• Chronic obstructive pulmonary disease , pulmonary hypertension (Pulmonary artery pressure> 60mmHg)

• Severe left or right valve disease.

• Pacemaker or implantable cardioverter defibrillator

• Myocardial infarction or revascularization in 3 months

• Anemia (hemoglobin <10 grams / dl) until 1 month before cardiopulmonary exercise testing

Related Conditions & MeSH terms

• Fibrosis
• Heart Failure
• Hypertrophy

Intervention

Other:
• Aerobic exercise in treadmill
30-40min of aerobic exercise in treadmill. The aerobic intensity will be established by heart rate levels that corresponded to anaerobic threshold up to 10% below the respiratory compensation point obtained in the cardiopulmonary exercise test. This intensity corresponded to 60-72% peak V?o2. During the exercise sessions, when a training effect will be observed, as indicated by a decrease by 8 to 10% in heart rate, the treadmill velocity or inclination will be increased to return to the target heart rate levels.
• Local strengthening exercises
15 min of local strengthening exercises will be performed in major muscle groups (legs, arms and trunk muscles): three series of each exercise, 12-15 repetitions.
• Stretching exercises
5-min stretching exercises will be performed in major muscle groups (legs, arms and trunk muscles)

Locations

Country	Name	City	State
Brazil	University of Campinas	Campinas	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Campinas, Brazil

Country where clinical trial is conducted

Brazil, 

References & Publications (44)

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* Note: There are 44 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial remodeling assessed by CMR in rehabilitation vs usual care.	Investigate whether rehabilitation compared to usual care is associated with significant favorable myocardial remodeling assessed by CMR determination of ECV.	4 months
Secondary	Change in left ventricular ejection fraction	Left Ventricular ejection fraction (%) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.	4 months
Secondary	Change in right ventricular ejection fraction	Right Ventricular ejection fraction (%) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.	4 months
Secondary	Change in left ventricular mass (absolute/index)	Left ventricular mass absolute (g) and index (g/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.	4 months
Secondary	Change in left ventricular diastolic volume (absolute/index)	Left ventricular diastolic volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.	4 months
Secondary	Change in right ventricular diastolic volume (absolute/index)	Right ventricular diastolic volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.	4 months
Secondary	Change in left ventricular systolic volume (absolute/index)	Left ventricular systolic volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.	4 months
Secondary	Change in right ventricular systolic volume (absolute/index)	Right ventricular systolic volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.	4 months
Secondary	Change in left ventricular stroke volume (absolute/index)	Left ventricular stroke volume absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.	4 months
Secondary	Change in right ventricular stroke volume (absolute/index)	Right ventricular stroke volume (absolute (ml) and index (ml/m2) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.	4 months
Secondary	Change in late gadolinium enhancement	Late gadolinium enhancement (LGE) will be determined by cardiac magnetic resonance using a previously describe inversion recovery sequence after 10-15 minutes of a cumulative dose of 0,2 mmol/kg of gadolinium diethylenetriamine pentaacetic acid. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.	4 months
Secondary	Change in LV mass/volume ratio	LV mass/volume ratio (g/mL) will be determined by cardiac magnetic resonance using a previously described cine steady-state free precession imaging. All patients will be imaged with ECG gating and breath holding in a supine position. Patients will be imaged at baseline and after 4 months of the intervention.	4 months
Secondary	Change in functional capacity	VO2max will be evaluated by cardiopulmonary test. Patients will performed the cardiopulmonary test at baseline and after 4 months of the intervention.	4 months
Secondary	Change in quality of life	Quality of life will be evaluated by numerical score of Minnesota Questionnaire.; Patients will performed the Minnesota Questionnaire at baseline and after 4 months of the intervention.	4 months
Secondary	Change in N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP)	Change in NT-proBNP with the intervention.	4 months
Secondary	Change in diastolic dysfunction assessed by transthoracic echocardiogram	Change in parameters of diastolic dysfunction assessed before and after the intervention.	4 months
Secondary	Change in cardiac sympathetic function	Change in cardiac sympathetic function assessed by cardiac uptake of metaiodobenzylguanidine (MIBG) labeled with I-123. Patients will performed the MIBG study at baseline and after 4 months of the intervention.	4 months
Secondary	Change in intracellular lifetime of water (tic - a marker of cardiomyocyte hypertrophy)	tic will be determined by cardiac magnetic resonance T1 measurements acquired before and after administration of gadolinium diethylenetriamine pentaacetic acid (0,2mmol/kg), at 2 different time points (baseline and 4-moths after the intervention)	4 months