[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100657480":3},{"organization":4,"outcomesModule":7,"designInfo":18,"detailedDescription":21,"studyPopulation":22,"armGroups":23,"interventions":17,"overallOfficials":17,"centralContacts":27,"locations":17,"responsibleParty":33,"collaborators":37,"id":44,"slug":45,"hasResults":46,"nctId":47,"briefTitle":48,"officialTitle":49,"acronym":17,"eligibilityCriteria":50,"healthyVolunteers":46,"sex":51,"minAge":52,"maxAge":53,"enrollmentInfo":54,"targetDuration":17,"studyType":57,"phases":17,"briefSummary":58,"conditions":59,"keywords":62,"overallStatus":68,"whyStopped":17,"lastUpdateSubmitDate":69,"lastUpdatePostDateStruct":70,"startDateStruct":73,"completionDateStruct":75,"leadSponsor":77,"locationsCount":17},{"fullName":5,"class":6},"Chang Gung Memorial Hospital","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":17},[9],{"measure":10,"description":11,"timeFrame":12},"Recurrent worsening heart failure (HF) event burden","Recurrent worsening heart failure (HF) event burden within 36 months after enrollment. Events include:\n\n1. Hospitalization for worsening HF\n2. HF worsening treated at emergency or outpatient clinic\n3. intensive diuretic care event\n4. All-cause death","within 36 months after enrollment",[14],{"measure":15,"description":16,"timeFrame":12},"Composite events","1. First hospitalization for worsening heart failure, emergency heart failure care, or all-cause death within 36 months\n2. Number of heart failure hospitalizations, number of emergency\u002Funexpected care visits, and total days of hospitalization within 36 months",null,{"allocation":17,"interventionModel":17,"interventionModelDescription":17,"primaryPurpose":17,"observationalModel":19,"timePerspective":20,"maskingInfo":17},"COHORT","PROSPECTIVE","I. Background:\n\nHeart 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 participants into grades I through IV based on the degree of limitation in physical activity. Participants 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.\n\nAmong 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.\n\nTherefore, this study focuses on phenylalanine and phenylpyruvate metabolites to assess their correlation with patient prognosis. In another part, the investigators 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.\n\nII. Objectives:\n\n1. To uniformly quantify phenylalanine and phenylpyruvate using high-order mass spectrometry and verify their correlation with the worsening of heart failure.\n2. To use the developed \"Risk Score\" in prospective, multicenter, observational validation studies (including Chang Gung Memorial Hospital, Mackay Memorial Hospital, Cheng Hsin General Hospital, and National Taiwan University Hospital) to assess its clinical predictive ability, calibration, discrimination, and cross-center generalization ability in participants with chronic outpatient heart failure.\n\nIII. Methods The investigators will enroll participants at outpatient clinic at different hospitals. Then, fasting blood (3 ml) will be collected once to get the plasma after centrifugation. Phenylpyruvate (PPA) concentration will be measured by liquid chromatography-mass spectrometry (LC-MS\u002FMS).\n\nBased on clinical information and the blood levels of NT-proBNP and PPA, a risk score will be calculated.\n\nFor clinical outcomes, the investigators will follow up participants' events of recurrent worsening heart failure, which will be explained in the primary and secondary outcome section.\n\nThe investigators will do statistical analysis to see the prognostic value of PPA concentrations and the risk scores.","Outpatients with chronic heart failure",[24],{"label":25,"type":17,"description":26,"interventionNames":17},"outpatients with chronic heart failure","Inclusion Criteria:\n\n* Adult men and women aged 18 to 85 years\n* 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.\n* Patients with a recorded left ventricular ejection fraction (LVEF) ≤ 40% in their medical history, but LVEF is not restricted at the time of admission to include patients with heart failure with reduced ejection fraction (HFrEF), heart failure with improved ejection fraction (HFimpEF), and those potentially progressing to heart failure with mildly reduced ejection fraction (HFmrEF)\u002F heart failure with preserved ejection fraction (HFpEF).\n* 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.",[28],{"name":29,"role":30,"phone":31,"phoneExt":17,"email":32},"Chao-Hung Wang, MD, PhD","CONTACT","0975360604","bearty54@gmail.com",{"type":34,"investigatorFullName":35,"investigatorTitle":36,"investigatorAffiliation":5,"oldNameTitle":17,"oldOrganization":17},"PRINCIPAL_INVESTIGATOR","CHAO-HUNG WANG, MD","MD, PhD, Professor",[38,40,42],{"name":39,"class":6},"National Taiwan University Hospital",{"name":41,"class":6},"Mackay Memorial Hospital",{"name":43,"class":6},"Cheng-Hsin General Hospital","100657480","biomarker-panel-development-for-early-identification-of-worsening-heart-failure-and-improved-post-acute-care-100657480",false,"NCT07838766","Biomarker Panel Development for Early Identification of Worsening Heart Failure and Improved Post-acute Care","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","Inclusion Criteria:\n\n* Adult men and women aged 18 to 85 years\n* 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.\n* Patients with a recorded left ventricular ejection fraction (LVEF) ≤ 40% in their medical history, but LVEF is not restricted at the time of admission to include patients with heart failure with reduced ejection fraction (HFrEF), heart failure with improved ejection fraction (HFimpEF), and those potentially progressing to heart failure with mildly reduced ejection fraction (HFmrEF)\u002F heart failure with preserved ejection fraction (HFpEF).\n* 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.\n\nExclusion Criteria:\n\n* 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.\n* Patients with New York Heart Association (NYHA) class IV and unstable clinical condition requiring frequent intravenous therapy or hospitalization.\n* Patients currently receiving maintenance hemodialysis or peritoneal dialysis.\n* 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.","ALL","18 Years","85 Years",{"count":55,"type":56},800,"ESTIMATED","OBSERVATIONAL","Heart failure is a complex clinical syndrome with high hospitalization rates and high mortality risks. While N-terminal-pro B-type natriuretic peptide (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.\n\nTherefore, the investigators 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.",[60,61],"Outpatients With Chronic Heart Failure","Heart Failure Chronic",[63,64,65,66,67],"outpatients","chronic heart failure","biomarker","phenylalanine","phenylpyruvate","NOT_YET_RECRUITING","2026-09-25",{"date":71,"type":72},"2026-09-29","ACTUAL",{"date":74,"type":56},"2026-09-18",{"date":76,"type":56},"2030-10-31",{"name":5,"class":6}]