Integration of Metabolic Assessment on Phenylalanine Axis and Clinical Databank-based Artificial Intelligence Computation in Heart Failure: Biomarker Panel Development for Early Identification of Worsening Heart Failure and Improved Post-acute Care
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 800
- 主要终点
- Recurrent worsening heart failure (HF) event burden
研究概览
简要总结
Heart failure is a complex clinical syndrome with high hospitalization rates and high mortality risks. While NT-proBNP is widely used in clinical practice to assist in diagnosis and assessment, its ability to detect prognosis in heart failure remains insufficient. Recent scientific research has found that phenylalanine in the blood and its endogenous toxic substance phenylpyruvate are closely related to impaired energy synthesis in heart muscle cells, making them highly promising next-generation long-term biomarkers. Our research team has previously developed a "risk score" prediction model that combines phenylpyruvate levels in the blood with clinical data; this project aims to further confirm its clinical value.
Therefore, we cordially invite heart failure patients who are being followed up in the cardiology outpatient clinic to have their "phenylalanine" and "phenylpyruvic acid" concentrations measured in a small amount of blood. This data, combined with clinical data, will be used to calculate a "Risk Score" to identify high-risk heart failure patients earlier.
详细描述
I. Background:
Heart failure is a complex syndrome. Any abnormality in cardiac structure or function that affects ventricular congestion or ejection can lead to heart failure. Clinically, heart failure is classified into four categories based on the presence or absence of abnormal left ventricular ejection fraction (LVEF): heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), heart failure with normal left ventricular ejection fraction (LVEF ≥ 50%), and heart failure with improved ejection fraction (HFimpEF) (previously LVEF ≤ 40%, followed by follow-up to LVEF > 40%). The New York Heart Association functional classification (NYHA Fc) further classifies patients into grades I through IV based on the degree of limitation in physical activity. Patients diagnosed with HFrEF who exhibit symptoms of NYHA Fc grades 2 to 4 require guideline-directed medical therapy (GDMT). However, a good assessment strategy for long-term follow-up after treatment remains lacking.
Among existing diagnostic and treatment strategies, NT-proBNP is the most widely used biomarker for diagnosis and prognostic assessment. However, its ability to identify early abnormalities of heart failure relapse, quantify metabolic abnormalities caused by heart failure, and detect endogenous toxicities caused by heart failure is still insufficient, and its assessment of heart failure prognosis is also imprecise. Elevated blood concentrations of phenylalanine and its metabolite phenylpyruvate are currently considered highly relevant to the pathophysiological mechanisms of heart failure exacerbation and can lead to the accumulation of phenylalanine and its downstream metabolite phenylpyruvate in the body fluids and tissues of heart failure patients, further worsening cardiac function. Furthermore, these metabolic disorders are closely associated with oxidative stress, mitochondrial dysfunction, and impaired energy synthesis. These alterations have been confirmed in animal models and clinical patients. They hold great potential as biomarkers for long-term monitoring by capturing early metabolic abnormalities and endogenous toxicities in heart failure.
Therefore, this study focuses on phenylalanine and phenylpyruvate metabolites to assess their correlation with patient prognosis. In another part, we used the Chang Gung database for data analysis and integrated metabolite testing and clinical data into a "Risk Score" to identify high-risk patients. This aims to provide heart failure patients with more precise metabolic assessment and clinical management tools, thereby improving their quality of life and reducing disease-related mortality and hospitalization rates.
II. Objectives:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(1) Adult men and women aged 18 to 85 years ( 2) Patients with chronic heart failure diagnosed as stage C or D in outpatient settings. Stage definitions are based on the American Heart Association Heart Failure Classification System (ACC/AHA HF classification system).
- •(3) Patients with a recorded LVEF ≤ 40% in their medical history, but LVEF is not restricted at the time of admission to include patients with HFrEF, HFimpEF, and those potentially progressing to HFmrEF/HFpEF.
- •(4) Patients who have recently been hospitalized for acute heart failure must be discharged and have been clinically stable for at least three months before inclusion.
排除标准
- •Patients with other serious comorbidities that significantly impact life expectancy or survival within three months based on clinical assessment, such as terminal cancer or severe multiple organ failure.
- •Patients with NYHA class IV and unstable clinical condition requiring frequent intravenous therapy or hospitalization.
- •Patients currently receiving maintenance hemodialysis or peritoneal dialysis.
- •Patients who are unable to complete basic follow-up, lack key clinical data, or do not consent to the use of the specimen and data.
研究组 & 干预措施
outpatients with chronic heart failure
Inclusion Criteria:
- Adult men and women aged 18 to 85 years
- Patients with chronic heart failure diagnosed as stage C or D in outpatient settings. Stage definitions are based on the American Heart Association Heart Failure Classification System (ACC/AHA HF classification system).
- Patients with a recorded LVEF ≤ 40% in their medical history, but LVEF is not restricted at the time of admission to include patients with HFrEF, HFimpEF, and those potentially progressing to HFmrEF/HFpEF.
- Patients who have recently been hospitalized for acute heart failure must be discharged and have been clinically stable for at least three months before inclusion.
结局指标
主要结局
Recurrent worsening heart failure (HF) event burden
时间窗: within 36 months after enrollment
Recurrent worsening heart failure (HF) event burden within 36 months after enrollment. Events include: 1. Hospitalization for worsening HF 2. HF worsening treated at emergency or outpatient clinic 3. intensive diuretic care event 4. All-cause death
次要结局
- Composite events(within 36 months after enrollment)
研究者
CHAO-HUNG WANG, MD
MD, PhD, Professor
Chang Gung Memorial Hospital