Heart Failure, Preserved Ejection Fraction
Conditions
Keywords
heart failure with preserved ejection fraction，HFpEF, Henggliflozin, Probiotics
Brief summary
HFpEF has a high incidence and lacks effective therapy, and its onset is closely related to systemic inflammation and intestinal dysbacteriosis.SGLT-2i exerts its effects by diuresis, anti-inflammatory and improving energy metabolism, whereas probiotics modulate intestinal flora, reduce inflammatory markers, and regulate immune responses.The combination of the two drugs is not only expected to exert synergistic therapeutic potential, but may also reduce the risk of sarcopenia associated with SGLT-2i weight loss.This study aims to combine henagliflozin and a probiotic preparation on the basis of standard anti-heart-failure therapy, and to observe their effects on cardiac and renal function, intestinal barrier function, quality of life, and exercise tolerance in elderly patients with HFpEF, while exploring the underlying mechanisms, so as to provide new data and therapeutic strategies for the treatment of elderly HFpEF patients.
Interventions
DRUGHenggliflozin Combined with Probiotics
Primary anti-HF therapy + Henagliflozin Proline Tablets (10mg, 1 times/day) + clostridial enterococcus triple live tablet (400mg, 3 times/day) orally, for 12 weeks.
DRUGHenggliflozin
Primary anti-HF therapy + Henagliflozin Proline Tablets (10mg, 1 times/day) + placebo (400mg, 3 times/day) orally, for 12 weeks.
DRUGdouble placebo
Primary anti-HF therapy +Two types of placebo tablets orally, for 12 weeks.
Sponsors
The First Affiliated Hospital of Air Force Medicial University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Age over 60 years; 2.Relevant investigations within 6 months meet diagnostic criteria for HFpEF: 1. epidemiologic and population characteristics of patients with HFpEF; 2. presence of symptoms and/or signs of heart failure; 3. Cardiac imaging suggests LVEF \>=50%; 4. BNP\>=35pg/ml and (or) NT-pro BNP\>=125pg/ml in sinus rhythm, and BNP\>=105pg/ml and (or) NT-pro BNP\>=365pg/ml in atrial fibrillation; 5. at least one of the following conditions is met: 1) LVMI\>=115 g/m\^2(male)or 95 g/m\^2(female); 2) LAVI\>34 ml/m\^2; 3) Relative wall thickness\>0.42;or left ventricular free wall thickness\>12mm; 4) E/e'\>=14; 5) Ventricular septal e'\<7cm/s, or lateral wall e'\<10cm/s, or mean e'\<8cm/s; 6) Tricuspid regurgitant velocity\>2.8m/s, or pulmonary artery systolic pressure\>35mmHg; 3.NYHA class II to III for cardiac function; 4. not taking SGLT-2 inhibitors within 6 months before enrollment; 5. no probiotic preparations taken within 3 months before enrollment; 6. The current anti-HF Therapeutic Regimen is well tolerated by patients and is stable for at least 1 month; 7. Currently stable HF with no acute exacerbations; 8. Cognitive Functioning is basically normal with comprehensible assessment scale content; 9. possess basic behavioral ability, being able to perform daily activities independently or with the help of accessory aids; 10. Understand the purpose of the Clinical Study, voluntarily participate and sign informed consent.
Exclusion criteria
* 1\. the patient's symptoms are due to noncardiac disease; 2. In those with contraindications to Henggliflozin: 1. those who are allergic to henggliflozin; 2. severe renal impairment (eGFR\<30ml/min/1.73m\^2), end-stage renal disease, or those requiring dialysis; 3. In those with contraindications to probiotics: <!-- --> 1. Patients with severe impairment of the intestinal barrier associated with sepsis, active massive bleeding from the digestive tract, perforation, and other causes. 2. those with current diagnosis of fulminant colitis or toxic megacolon. 3. Enteral feeding that cannot tolerate 50% caloric requirement due to severe diarrhea, significant fibrous intestinal stenosis, severe gastrointestinal bleeding, high-flow intestinal fistula, etc. 4. Patients with congenital or acquired immune deficiency. 5. Those recently treated with high-risk immunosuppression or cytotoxic drugs: e.g., continued use of rituximab, doxorubicin, or a medium-to high-dose steroid hormone (20 mg/d prednisone or higher) for more than 4 weeks. 6. Severe immunosuppression: Neutrophils \<1 500/mm\^3. 4. had a myocardial infarction within 6 months before enrollment, had a coronary artery bypass graft procedure, or had any event that could reduce LVEF (unless an LVEF \>=50%) confirmed; 5. valve replacement surgery within 6 months before enrollment; 6.Poor blood pressure control (SBP\>=180mmHg or DBP\>=100 mmHg); 7. Current acute decompensated heart failure requires treatment; 8. Resting heart rate exceeding 120 beats/min, or complicated by malignant Arrhythmia; 9. Significant coronary artery lesions require PCI revascularization; 10. Severe renal insufficiency (blood creatinine, Cr \>442μmol/L) or receiving dialysis treatment; 11. Patients with urinary tract infection at entry; symptoms and signs of urinary tract infection, such as urinary tract irritation signs (frequent urination, painful urination, urgency), pain and tenderness above the pubic bone, fever, pain or percussion pain in the waist, etc., and urine bacterial culture colony counts \>=105/ml; 12. currently having a malignancy that requires treatment; 13. Current concurrent acute disease or acute exacerbation of chronic disease; 14.Participated in other interventional investigators within 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kansas City Cardiomyopathy Questionnaire (KCCQ)scale score | Baseline, Week 4, Week 8,Week 12 | The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a validated patient-reported outcome measure used to assess heart failure-specific quality of life. The change in the overall summary score from baseline to Week 12 will be compared between the groups. Higher scores indicate better health status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nutritional Status Using the Mini Nutritional Assessment (MNA) Scale | Baseline, Week 4, Week 8, Week 12 | Nutritional status will be evaluated using the Mini Nutritional Assessment (MNA) scale. Changes in total score from baseline to Week 12 will be compared. |
| Basic Activities of Daily Living (BADL) Scale Score | Baseline, Week 4, Week 8, Week 12 | The BADL scale will be used to assess changes in patients' functional independence in daily activities. |
| SARC-F Scale Score | Baseline, Week 4, Week 8, Week 12 | The SARC-F questionnaire is a validated tool for sarcopenia screening, assessing strength, assistance with walking, rising from a chair, climbing stairs, and falls. Changes in total score from baseline to Week 12 will be evaluated. |
| Fecal Short Chain Fatty Acids (SCFAs) | Baseline, Week 12 | Concentrations of fecal short-chain fatty acids, including acetate, propionate, and butyrate, will be quantified to assess changes in gut microbial fermentation. |
| Serum Trimethylamine-N Oxide (TMAO) | Baseline, Week 12 | Serum TMAO levels will be measured as a marker of gut microbiota-dependent metabolism of dietary phosphatidylcholine and carnitine. |
| Serum Bile Acids Profile | Baseline, Week 12 | Concentrations of primary and secondary bile acids, such as cholic acid and deoxycholic acid, will be quantified to evaluate changes in bile acid metabolism. |
| White Blood Cell (WBC) Count | Baseline, Week 12 | WBC count will be measured to monitor changes in systemic inflammatory/immune status. |
| Hemoglobin (HGB) Concentration | Baseline, Week 12 | Hemoglobin concentration will be measured to assess changes in oxygen-carrying capacity. |
| Platelet (PLT) Count | Baseline, Week 12 | Platelet count will be measured to evaluate changes in hemostatic/thrombotic potential. |
| Serum Creatinine | Baseline, Week 12 | Serum creatinine level will be measured to assess renal function. |
| Estimated Glomerular Filtration Rate (eGFR) | Baseline, Week 12 | eGFR will be calculated as a marker of renal function. |
| Alanine Aminotransferase (ALT) | Baseline, Week 12 | Serum ALT level will be measured to assess hepatocellular integrity. |
| Aspartate Aminotransferase (AST) | Baseline, Week 12 | Serum AST level will be measured to assess hepatocellular integrity. |
| Fasting Blood Glucose | Baseline, Week 12 | Fasting blood glucose concentration will be measured to assess glycemic status. |
| Serum Electrolytes (Sodium, Potassium, Chloride) | Baseline, Week 12 | Serum concentrations of sodium, potassium, and chloride will be measured. Each electrolyte will be analyzed separately for changes from baseline. |
| Left Atrial Volume Index (LAVI) | Baseline, Week 12 | LAVI will be measured to assess changes in left atrial remodeling. |
| Left Ventricular Mass Index (LVMI) | Baseline, Week 12 | LVMI will be measured to assess changes in left ventricular hypertrophy. |
| Pulmonary Artery Systolic Pressure (PASP) | Baseline, Week 12 | PASP will be measured to assess changes in pulmonary artery pressure. |
| E/e' Ratio | Baseline, Week 12 | The E/e' ratio will be measured to assess changes in left ventricular filling pressure. |
| Total Body Fat Mass | Baseline, Week 12 | Body fat mass will be measured to assess changes in adiposity. |
| NYHA functional classification | Baseline, Week 4, Week 8,Week 12 | The New York Heart Association (NYHA) functional classification is used to assess the severity of heart failure symptoms. Changes in NYHA class from baseline to Week 12 will be compared between groups. |
| 6-Minute Walk Test (6MWT) Distance | Baseline, Week 4, Week 8, Week 12 | The 6-minute walk test is a measure of functional capacity in patients with heart failure. The distance walked in 6 minutes will be assessed at baseline, Week 4, Week 8,and Week 12 to evaluate changes in exercise tolerance. |
| Serum N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) Level | Baseline, Week 4, Week 8,Week 12 | Serum NT-proBNP is a key biomarker for heart failure severity. Levels will be measured at baseline, Week 4, Week 8, and Week 12 to assess changes in cardiac strain. |
| Minnesota Living with Heart Failure Questionnaire (MLHFQ) Total Score | Baseline, Week 4, Week 8,Week 12 | The MLHFQ is a patient-reported questionnaire evaluating the impact of heart failure on quality of life. Higher scores indicate greater impairment. Changes from baseline to Week 12 will be compared. |
| Serum Inflammatory Biomarkers (NLRP3, IL-1β, TNF-α, IL-6, MCP-1, ICAM-1, VCAM-1) | Baseline, Week 4, Week 8, Week 12 | Serum levels of the following inflammatory and endothelial activation markers will be measured to assess the effect of drugs on systemic inflammation in patients with HFpEF: NLRP3, IL-1β, TNF-α, IL-6, MCP-1, ICAM-1, and VCAM-1. Each biomarker will be analyzed separately for changes from baseline. |
| Frailty Status Using the Fried Frailty Phenotype Criteria | Baseline, Week 4, Week 8, Week 12 | Frailty status will be assessed using the Fried criteria to evaluate changes in physical vulnerability. |
| Gut Microbiota Composition and Diversity | Baseline, Week 4, Week 8, Week 12 | Fecal samples will be collected for 16S rRNA sequencing to analyze changes in gut microbiota composition, diversity, and taxonomic profiles following drugs intervention. |
Countries
China
Contacts
CONTACTJiChenyang
Outcome results
None listed