Targeting LOXL2 and Cardiac Fibrosis for Post-acute Heart Failure Treatment- A Prospective Study

Heart Failure; With Decompensation Clinical Trial

Official title:

Targeting LOXL2 and Cardiac Fibrosis for Post-acute Heart Failure Treatment- A Prospective Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05498584
• Other study ID #: 202002486B0A3
• Status: Recruiting
• Start date: August 25, 2022
• Est. completion date: August 30, 2026

Study information

• Verified date: August 2022
• Source: Chang Gung Memorial Hospital
• Contact: Hsin-Yen Tsai
• Phone: +886929610850
• Email: milktea588[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: August 30, 2026
• Est. primary completion date: August 30, 2025
• Gender: All
• Age group: 20 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Heart Failure
• Heart Failure; With Decompensation

Intervention

Behavioral:
• exercise based cardiac rehabilitation
The types of exercise are treadmill walking/walking-jogging/jogging, ergometer cycling, stair climbing, or elliptical machine training. The training intensity is gradually increased fortnightly to reach the targeted Borg's rate of perceived exertion (RPE) of 12-14. The training duration is 40 minutes, which included 5-10 minutes of warm-up and cool-down exercises. The training frequency is three sessions per week, with 36 sessions concluding a complete course.

Locations

Country	Name	City	State
Taiwan	Chang Gung Memorial Hospital Heart Failure Center	Kaohsiung

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	all-cause mortality	Number of Participants That Had First Occurrence of the All-cause mortality	up to 36 months
Secondary	HF readmission	Number of participants that had first occurrence of the HF readmission.	up to 12 months
Secondary	enothelial function improvement	changes of FMD from baseline to 6 months	up to 6 months
Secondary	Change From Baseline to Month 6 and Month 12 for the Kansas City Cardiomyopathy Questionnaire 12 (KCCQ 12) Clinical Summary Score	Change from baseline to Month 6 and month 12 for the Kansas City Cardiomyopathy Questionnaire short form (KCCQ12) clinical summary score. KCCQ12 is a 12-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. KCCQ12 clinical summary score is a composite assessment of physical limitations and total symptom scores. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	Baseline, Month 6 , Month 12]