Cardiovascular Diseases, Chronic Heart Failure
Conditions
Keywords
Lymphatic Decompression, Chronic Heart Failure, Stenting, Lymphatic system
Brief summary
The main objective is to evaluate the safety of lymphatic decompression in heart failure. The research hypothesis is that lymphatic decompression is safe and feasible in heart failure patients with recurrent congestion despite on maximum tolerated diuretic dosage. Safety will be evaluated by the rate and severity of adverse events. Feasibility will be assess based on procedural success and time. In demonstrating that this approach is both safe and feasible, the expected benefits of the research include symptom relief for patients as well as data generation and considerations for a novel treatment for chronic heart failure patients. Ultimately, this research will contribute to the development of an additional treatment option for patients that remain congested while on standard-of-care therapies.
Detailed description
Better understanding of the lymphatic system's role in managing volume status and how this system is overwhelmed in HF has made it a compelling target for intervention. Historic and contemporary preclinical and clinical evidence demonstrate that surgically relieving or bypassing the resistance at the LVJ when the lymphatic system is overwhelmed significantly improves volume status in heart failure. Although it demonstrates clinical benefit in a majority of patients, the surgical approach has greater risks and is not scalable due to technical difficulties. More recently, improved clinical outcomes and feasibility of minimally invasive lymphatic decompression via transcatheter thoracic duct stenting was demonstrated in cirrhosis, another volume-overload related condition. With supportive preclinical and clinical data, this study aims to evaluate lymphatic decompression in heart failure.
Interventions
PROCEDURELymphatic Decompression
Patients will be prepared according to standard procedures Clinical examinations, para-clinical assessment and biological tests Patient will be set in angiography room and local anesthesia at the puncture area (femoral vein or brachial vein). Obtain access to the femoral vein per standard procedures (option for brachial access depending on anatomy based on pre-operative CT, per physician discretion) After setting introducer sheath, catheterism of cardiac cavity will be performed for assess the following standard hemodynamic measures Catheterism of thoracic duct through the subclavian vein will be performed under fluoro guidance and phlebography using contrast Measure TD and central venous pressures Deploy stent under fluoro guidance Standard vascular stent deployed in subclavian vein and into lymphovenous junction Evaluate the procedure with standard phlebography and hemodynamic measures Remove catheters, and temporary compression as standard venous procedures
Sponsors
Selera Medical
University Hospital, Grenoble
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects ≥18 years of age * Diagnosis of chronic heart failure (reduced or preserved EF) with evidence of diastolic dysfunction on echocardiogram * Chronic NYHA class II or greater * Prone to cardiorenal syndrome or refractory to diuretics (e.g. on lasix 125 mg PO total daily dose or equivalent diuretic dosing for 1 or more months prior to enrollment) * History of symptoms of congestion (e.g. dyspnea, peripheral edema, pleural effusion, and/or ascites) in preceding 12 months requiring HF hospitalization with IV diuresis * NT-proBNP \>1000 pg/ml * eGFR \> 20 ml/min/1.73m2 * Life expectancy \> 6 months * Membership of the social security system or benefiting from such a system * Able and willing to sign informed consent
Exclusion criteria
* Anatomy not considered suitable based on CT with contrast (e.g., not visible, multiple terminal ducts or plexiform termination) * Other cause of thoracic duct congestion based on CT with contrast (superior cava vein/left brachiocephalic vein/ jugular or subclavian vein thrombosis) * Acute coronary syndrome, stroke, pulmonary embolism in previous 6 months * Stage IV or stage V chronic kidney disease, or end-stage renal disease (ESRD) requiring dialysis, or severe renal failure (\<30ml/min) * Cardiac surgery within past 6 months (coronary artery bypass grafting, valvular, or pericardial surgery) * Transcatheter structural heart intervention within past 6 months * Active pregnancy, breastfeeding, or anticipated pregnancy within 1 year * Known coagulation disorders or inability to take blood thinning medications (anticoagulation or antiplatelet therapy) for at least one month after procedure * Severe pulmonary hypertension (RVSP \>60mmHg as assessed by echocardiogram) * Severe RV dysfunction (TAPSE \<17mm, RFAC \<35%) * Known allergies or sensitivities to materials utilized in procedure, including contrast agents * Candidate deemed unsuitable based on investigator opinion * Subject in exclusion period of another study * Subject under administrative or judicial supervision * Subject unable to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the lymphatic decompression's safety in heart failure by the assessment of the rate and severity of adverse events after the procedure of thoracic duct decompression. | During 180 days after the procedure +/- 4 days | Assessment of the rate and severity of adverse events after the procedure of thoracic duct decompression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (urine output) | During 180 days after the procedure +/- 4 days | Change in HF symptoms, including urine output (mL) |
| To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (sodium output) | During 180 days after the procedure +/- 4 days | Change in HF symptoms, including sodium output (mmol/L/24h) |
| To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (medication dosing requirements). | During 180 days after the procedure +/- 4 days | Change in HF symptoms, including medication dosing requirements |
| To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (KCCQ quality of life score) | During 180 days after the procedure +/- 4 days | Change in HF symptoms, including KCCQ quality of life score (scaled from 0 to 100 and represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent). |
| To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (EVEREST congestion score) | During 180 days after the procedure +/- 4 days | Change in HF symptoms, including EVEREST congestion score (based on specific symptoms and signs ranges from 0 to 3 for each symptom or sign) |
| To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (6-min walk test) | During 180 days after the procedure +/- 4 days | Change in HF symptoms, including 6-min walk test (The distance in metres walked reflects the patient's functional capacity) |
| Evaluation of the lymphatic decompression's feasibility in heart failure | Procedure day (D0-1) | Lymphatic decompression's success (Y/N) |
| To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (IV diuresis rates) | During 180 days after the procedure +/- 4 days | Change in HF symptoms, including IV diuresis rates (mg/day) |
| To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (frequency of paracentesis) | During 180 days after the procedure +/- 4 days | Change in HF symptoms, including frequency of paracentesis (mg/L) |
| To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (frequency of thoracentesis) | During 180 days after the procedure +/- 4 days | Change in HF symptoms, including frequency of thoracentesis (mg/L) |
| Evaluation of the lymphatic decompression's impact on thoracic duct pressure | Before the procedure and days 90 +/- 4 days after the procedure | Change in pressure gradient across lymphovenous junction before and after stenting |
| Evaluation of the lymphatic decompression's impact on central hemodynamic functions. (Blood flow dynamics in mmHg). | Days 30, Days 90 and days 180 after the procedure | Changes in hemodynamic measures during intervention evaluated by catheter in right cavities before decompression, 30 minutes after decompression and 3 months after the procedure. |
| Evaluation of the lymphatic decompression's impact on renal function | Days 30, Days 90 and days 180 after the procedure | Changes in creatinine / eGFR before and after the procedure (M1, M3, M6). |
| To evaluate the lymphatic decompression's efficacy in heart failure by change in heart failure symptoms. (number of heart failure hospitalization) | During 180 days after the procedure +/- 4 days | Change in HF symptoms, including number of HF hospitalization |
Outcome results
None listed