Strategy, Efficacy and Safety of Medication Usage in Heart Failure Patients Who Were Intolerable to GDMT

Study Overview
=================
Brief Summary
-----------------
SEMI trial is a single-center, observational, prospective cohort study. The study enrolled acute heart failure patients admitting to the hospital and intended to accept heart failure therapy. The current guideline recommend ACEI/ARB/ARNI, β blocker, SGLT2i and MRA as the cornerstone medication of HFrEF therapy, but a part patients were intolerable to GDMT because of hypotension, hyperkalemia or renal insufficency. Vericiguat is a new medication therapy choice for the patients with heart failure with reduced ejection fraction (HFrEF), it may has less influence on blood pressure, it is unkonwn about the efficacy and safety of vericiguat in patients who were intolerable to GDMT.

Detailed Description
-----------------
The study aim to provide evidence of medication strategy in heart failure patients, especially for patients who are intolerable for GDMT.

Official Title
-----------------
Medication Strategies in Heart Failure Patients Who Are Intolerable to Guideline-directed Medical Therapy

Conditions
-----------------
Heart Failure With Reduced Ejection Fraction

Intervention / Treatment
-----------------
* Other: Guideline-Directed Medication Treatment (GDMT)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Age ≥ 18 years Hospitalization and diagnosed with acute heart failure with typical symptoms and signs, such as dyspnea, shortness of breath and edema. LVEF measured by echocardiogram ≤ 45%. Patients with elevated NT-proBNP (NT-proBNP ≥ 125 pg/ml in sinus rate or ≥ 350 pg/ml in atrial fibrillation) Exclusion criteria: LVEF measured by the UCG>45% Used to diagnosed with heart failure with preserved ejection fraction. Age ≤18 years. Using or planned to be implanted with a ventricular assist device. Severe and uncontrolled pulmonary disease, such as pneumoconiosis, newly developed pulmonary embolism, or chronic obstructive pulmonary disease requiring long-term oxygen therapy. Severe and uncontrolled liver disease with Child-Pugh class C. History of allergic or hypersensitivity to ACEIs, ARBs, ARNI, β blockers, SGLT2is, MRAs and vericiguat. Patients diagnosed with active myocarditis. Probable alternative diagnoses could account for the patient's HF symptoms e.g., bronchial asthma, primary pulmonary hypertension. Pregnant woman Fatal or uncontrollable heart arrythmia e.g., symptomatic or persistence ventricular tachycardia, ventricular rate>150 bpm in AF patients. Obvious stenosis of bilateral renal arteries.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Heart Failure Patients who were tolerable to GDMT<br>Guideline-Directed Medication Treatment contains ACEI/ARB/ARNI, β blocker, SGLT2i and MRA. The patients in this group were tolerable to all the medications and accepted GDMT. | Other: Guideline-Directed Medication Treatment (GDMT)<br>* GDMT contains ACEIs/ARBs/ARNI, β blockers, SGLT2is, MRAs. ACEI/ARB/ARNI and β blocker will gradually be titrated up to the maximum tolerable dose<br>|
| Heart Failure Patients who were intolerable to GDMT<br>The patients in this group were intolerable to one or more medication in GDMT due to hypotension, hyperkalemia or renal insufficiency. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality or worsening heart failure in 180 days | Risk of all-cause death, readmission due to heart failure or accepting intravenous diuretic therapy in 180 days | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in symptoms and signs of heart failure | Change in symptoms and signs of heart failure measured by New York Heart Association (NYHA) class 1 to 4 | 180 days | 
| Change in N-terminal pro-B type natriuretic peptide | Change in NT-proBNP level from baseline to 180 days or endpoint | 180 days | 
| Change in left ventricular ejection fraction (LVEF) | Change in LVEF measured by echocardiogram from baseline to 180 days or endpoint | 180 days | 
| Change in left ventricular end-diastolic diameter (LVEDD) | Change in LVEDD measured by echocardiogram from baseline to 180 days or endpoint | 180 days | 
| Change in left ventricular end-systolic diameter (LVESD) | Change in LVESD measured by echocardiogram from baseline to 180 days or endpoint | 180 days | 
| Change in left ventricular fractional shortening (LVFS) | Change in LVFS measured by echocardiogram from baseline to 180 days or endpoint | 180 days | 
| Change in blood pressure | Systolic and diastolic blood pressures were measured at admission, discharge, and up-titration to the maximum tolerated dosage | 180 days | 
| Change in blood potassium | Blood potassium were measured in baseline and endpoint | 180 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
heart failure, myocardial fibrosis, vericiguat