Heart Failure Clinical Trial
Official title:
The Role of Nuclear Imaging in Heart Failure: Correlation With Cardiac Function and Metabolism, Biomarkers and Clinical Prognosis
Heart failure is a clinical syndrome of exercise intolerance and/or congestion. The potential roles of myocardial perfusion and metabolic abnormalities in subjects with cardiovascular risks, metabolic disease and heart failure assessed by nuclear dynamic imaging warrant further investigations. The study investigators propose that microvascular dysfunction and abnormal metabolic substrate shift precedes and triggers the onset of diastolic dysfunctions. The aims are (1) to develop and validate the noninvasive measurement of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) by using dynamic imaging with a CZT camera, (2) to assess myocardial glucose metabolism by using 18F-FDG dynamic PET, and MBF, MFR and LV systolic and diastolic function by dynamic SPECT comprehensively in subjects at cardiovascular risks and metabolic disease, HFrEF and HFpEF, (3) to correlate with peripheral serum markers and blood mononuclear cells subsets with myocardial perfusion and metabolic abnormalities, and (4) to test the hypothesis of these imaging and blood markers in diagnosis and prognostic implications. The study investigators also assess myocardial metabolic utilization in healthy and mice model of different metabolic disorders (obesity, diabetes mellitus and hypertension) by using 18F-FDG dynamic micro PET/CT, as an in-vivo measures which could be used to better understanding the disease mechanism and evaluating therapeutic strategies.
Heart failure (HF) is a clinical syndrome of exercise intolerance and/or congestion. The
management of heart failure with reduced ejection fraction (HFrEF) has improved over the last
decades. In contrast, little progress has been made in identifying evidence-based, effective
treatments for heart failure with preserved ejection fraction (HFpEF, LVEF >50%). Treatments
proven effective in HFrEF have failed to show significant benefit in patients with HFpEF.
Potential contributors include an incomplete understanding of pathophysiology and poor
matching of therapeutic mechanisms. The challenges of the use of diagnostic criteria,
prognostic evaluation and treatment highlight the need for more research in this field.
This portion of HFpEF consists predominantly older age and high prevalence of co-morbidity
such as overweight/obesity, diabetes mellitus, hyperlipidemia, metabolic syndrome and
hypertension. The systemic pro-inflammatory state may induce coronary endothelial
inflammation, microvasular dysfunction, myocardial substrate shift, myocardial and
interstitial fibrosis that contribute to high diastolic left ventricular stiffness and HF
development. Myocardial metabolic and perfusion imaging is a vital tool for understanding the
physiologic consequences of HF. Absolute myocardial blood flow (MBF) and myocardial flow
reserve (MFR) provide incremental diagnostic and prognostic information over relative
perfusion alone. Recent development of dedicated cardiac SPECT cameras with better
sensitivity and temporal resolution make dynamic SPECT imaging more practical. Quantitative
18F-FDG PET could be used as a means to measure myocardial metabolic changes. The study
investigators propose that microvasular dysfunction and abnormal metabolic substrate shift
precedes and triggers the onset of diastolic dysfunctions. The potential roles of myocardial
perfusion and metabolic abnormalities in subjects with cardiovascular risks, metabolic
disease and HFpEF assessed by nuclear dynamic imaging warrant further investigations.
The present project aims (1) to develop and validate the noninvasive measurement of absolute
myocardial blood flow (MBF) and myocardial flow reserve (MFR) by using dynamic imaging with a
CZT camera, (2) to assess myocardial glucose metabolism by using 18F-FDG dynamic PET, and
MBF, MFR and LV systolic and diastolic function by dynamic SPECT comprehensively in
participants at cardiovascular risks and metabolic disease, HFrEF and HFpEF, (3) to correlate
with peripheral serum markers and blood mononuclear cells subsets with myocardial perfusion
and metabolic abnormalities, and (4) to test the hypothesis of these imaging and blood
markers in diagnosis and prognostic implications. The study investigators also assess
myocardial metabolic utilization in healthy and mice model of different metabolic disorders
(obesity, diabetes mellitus and hypertension) by using 18F-FDG dynamic micro PET/CT, as an
in-vivo measures which could be used to better understanding the disease mechanism and
evaluating therapeutic strategies.
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