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
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Myocardial remodeling assessed by CMR in rehabilitation vs usual care.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Conventional Clinical Care - HFpEF
Heart Failure patients with preserved ejection fraction (HFpEF) randomized to this arm will keep receiving their conventional clinical care, being instructed to continue and maintain their usual daily activities.
Supervised Exercise Training- HFpEF
Heart Failure patients with preserved ejection fraction (HFpEF) randomized to this arm will keep receiving their conventional clinical care and participate in a supervised, facility based training program consisting of stretching exercises and aerobic exercise in treadmill.
干预措施: Aerobic exercise in treadmill (Other)
Supervised Exercise Training- HFpEF
Heart Failure patients with preserved ejection fraction (HFpEF) randomized to this arm will keep receiving their conventional clinical care and participate in a supervised, facility based training program consisting of stretching exercises and aerobic exercise in treadmill.
干预措施: Local strengthening exercises (Other)
Supervised Exercise Training- HFpEF
Heart Failure patients with preserved ejection fraction (HFpEF) randomized to this arm will keep receiving their conventional clinical care and participate in a supervised, facility based training program consisting of stretching exercises and aerobic exercise in treadmill.
干预措施: Stretching exercises (Other)
Conventional Clinical Care - HFrEF
Heart Failure patients with reduced ejection fraction (HFrEF) randomized to this arm will keep receiving their conventional clinical care, being instructed to continue and maintain their usual daily activities.
Supervised Exercise Training - HFrEF
Heart Failure patients with reduced ejection fraction (HFrEF) randomized to this arm will keep receiving their conventional clinical care and participate in a supervised, facility based training program consisting of stretching exercises and aerobic exercise in treadmill.
干预措施: Aerobic exercise in treadmill (Other)
Supervised Exercise Training - HFrEF
Heart Failure patients with reduced ejection fraction (HFrEF) randomized to this arm will keep receiving their conventional clinical care and participate in a supervised, facility based training program consisting of stretching exercises and aerobic exercise in treadmill.
干预措施: Local strengthening exercises (Other)
Supervised Exercise Training - HFrEF
Heart Failure patients with reduced ejection fraction (HFrEF) randomized to this arm will keep receiving their conventional clinical care and participate in a supervised, facility based training program consisting of stretching exercises and aerobic exercise in treadmill.
干预措施: Stretching exercises (Other)
结局指标
主要结局
Myocardial remodeling assessed by CMR in rehabilitation vs usual care.
时间窗: 4 months
Investigate whether rehabilitation compared to usual care is associated with significant favorable myocardial remodeling assessed by CMR determination of ECV.
次要结局
- Change in left ventricular mass (absolute/index)(4 months)
- Change in quality of life(4 months)
- Change in left ventricular diastolic volume (absolute/index)(4 months)
- Change in right ventricular systolic volume (absolute/index)(4 months)
- Change in left ventricular systolic volume (absolute/index)(4 months)
- Change in left ventricular stroke volume (absolute/index)(4 months)
- Change in functional capacity(4 months)
- Change in left ventricular ejection fraction(4 months)
- Change in late gadolinium enhancement(4 months)
- Change in diastolic dysfunction assessed by transthoracic echocardiogram(4 months)
- Change in intracellular lifetime of water (τic - a marker of cardiomyocyte hypertrophy)(4 months)
- Change in right ventricular ejection fraction(4 months)
- Change in right ventricular diastolic volume (absolute/index)(4 months)
- Change in right ventricular stroke volume (absolute/index)(4 months)
- Change in cardiac sympathetic function(4 months)
- Change in LV mass/volume ratio(4 months)
- Change in N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP)(4 months)
研究者
Otavio Rizzi Coelho Filho
Assistant Professor
University of Campinas, Brazil