Clinical trial NCT05498584: Targeting LOXL2 and Cardiac Fibrosis for Post-acute Heart Failure Treatment- A Prospective Study
Official title: Targeting LOXL2 and Cardiac Fibrosis for Post-acute Heart Failure Treatment- A Prospective Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Failure; With Decompensation
Keywords: heart failure
cardiac fibrosis
cardiac rehabilitation
endothelial function
cardiopulmonary exercise test
cardiac MRI
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2022-08-12
Enrollment: 130
Sex: ALL
Minimum age (years): 20
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study has a target enrollment of 126 HF patients admitted for worsening heart failure (HF) in 3 years, based on at least one symptom of HF and at least two signs of HF, and a change in medical treatment specifically targeting acute decompensated HF. We enroll those patients with reduced ejection fraction (LVEF \<=40%). Patients must be at least 20 years of age or greater, able to walk at the time of enrollment, and expected to be discharged to home.

Brief summary: A previous study demonstrated that a multidisciplinary cardiac rehabilitation (CR) program was associated with reduced medium- to long-term all-cause mortality in a retrospective propensity score-matched study. The investigators will further investigate the predictors including LOXl2, cardiac MRI, and endothelial function that will benefit from a successful CR.

Detailed description: Acute heart failure (HF) is a major cause of morbidity and mortality worldwide. The Taiwan national health insurance launched HF post-acute care program with a multi-discipline treatment strategy to improve care quality and reduce the readmission rate on July 1, 2017. A previous study showed heart failure disease management program (HFDMP) is beneficial for reducing recurrent events of HF readmission, especially in the ischemic cardiomyopathy population. The key element of HFDMP is cardiac rehabilitation and exercise training. Lysyl oxidase-like 2 (LOXl2) is an enzyme, which crosslinks collagen in fibrotic processes such as liver cirrhosis, lung fibrosis, cardiac fibrosis, and heart failure. An animal study showed the correlation between cardiac fibrosis and LOXl2 serum level. In a previous clinical prospective cohort study (CMRPG8H1271), the investigators recruited 40 patients who were discharged from acute decompensated heart failure. During the follow-up period, 10 patients suffered from cardiovascular mortality. The investigators found that the LOXl2 level is higher in patients with mortality than without.

Cardiac fibrosis is characterized by systolic or diastolic dysfunction that results from the accumulation of extracellular connective tissue proteins in the heart's interstitium. Both clinical evidence and experimental studies have suggested that fibrotic changes in the heart are reversible.

The investigators hypothesize that multi-disciplinary cardiac rehabilitation could reverse cardiac fibrosis by decreasing LOXl2 levels and improving endothelial function via reversing endothelial to mesenchymal transition (EndMT). The investigators will enroll 126 post-acute HF patients in 3 years. The investigators will follow up on endothelial function, and LOXl2 level 6 months later. The investigators will also arrange cardiac MRI sequences, such as balanced steady-state free precession (SSFP) and late gadolinium enhancement (LGE) for the diagnosis of cardiac fibrosis. A cardiopulmonary exercise test will be arranged after discharge for phase II cardiac rehabilitation. The investigators will use all-cause mortality and HF hospitalization as our primary endpoint, life quality scores (KCCQ12), and peak VO2/kg as our secondary endpoint.

Eligibility criteria: Inclusion Criteria:

1. Patients must give written informed consent before any assessment is performed.
2. Inpatients \>= 20 years of age, male or female.
3. Patients with a diagnosis of heart failure New York Heart Association (NYHA) class II-IV with BNP \>=100 pg/mL or NT-porBNP \>= 400 pg/mL ( \>= 900 pg/mL if concomitant atrial fibrillation)
4. Left ventricular ejection fraction \<= 40% by echocardiography or other methods

Exclusion Criteria:

1. Estimated survival time \< 6 months
2. Long-term bedridden for more than 3 months
3. Cannot tolerate exercise test due to muscular skeletal disorder.
4. Cannot cooperate all functional studies
5. Ventilator dependent
6. Terminal heart status
7. Family rejects to participate in this project
8. Primary severe valvular heart disease

Primary outcomes:
measure: all-cause mortality
timeFrame: up to 36 months
Secondary outcomes:
measure: HF readmission
timeFrame: up to 12 months
measure: enothelial function improvement
timeFrame: up to 6 months
measure: Change From Baseline to Month 6 and Month 12 for the Kansas City Cardiomyopathy Questionnaire 12 (KCCQ 12) Clinical Summary Score
timeFrame: Baseline, Month 6 , Month 12]
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital Heart Failure Center
Study officials:
affiliation: Chang Gung Medical Foundation
name: Shyh-Ming Che, MD
role: PRINCIPAL_INVESTIGATOR
References: