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Corresponding author: Mathieu Bernier, MD Quebec Heart and Lung Institute, Laval University, 2725 chemin Ste-Foy.G1V4G5, Quebec City, Quebec, Canada Québec City, QC, Canada
The lymphatic system is intricately linked to clinical manifestations of heart failure (HF). Unfortunately, this complex drainage network is commonly neglected in the pathophysiology and treatment of venous congestion and interstitial oedema. The following case illustrates the safety and feasibility of percutaneous lymphatic drainage to treat clinical manifestations of HF.
INTRODUCTION
Oedema occurs when excessive volume of fluid accumulates in the tissues: either cells or interstitial space. Several factors can lead to interstitial oedema: changes in hydrostatic or oncotic pressure, alterations of the molecular structure of the barrier (changes in hydraulic conductance or surface), and finally alterations in the lymphatic outflow system. Fluid leakage out of the capillaries to the interstitial space occurs physiologically for tissue hydration and nutrition. The lymphatic vascular system participates in interstitial volume homeostasis by scavenging liters of interstitial water and protein per day, and returning them to the venous circulation via lymphatic ducts located in the subclavian veins. Apart from its role in tissue fluid homeostasis, the lymphatic vascular system is a complex network involved in the transport of immune cells and antigens responsible for adaptative immunity.
The lymphatic system is commonly overlooked when considering the pathophysiology of heart failure (HF). Yet, most HF hospitalizations and symptoms are related to manifestations of venous congestion rather than low cardiac output. Numerous mechanisms contributing to interstitial fluid accumulation with the involvement of the lymphatic system have been previously described
: higher capillary hydrostatic pressure, decrease drainage (due to an increase central vein pressure), impaired lymph vessel integrity/compliance and maladaptive lymphangiogenesis. Hence, tissue congestion occurs when the lymphatic vascular system fails to compensate for the capillary hydrostatic pressure and increase filtration volume in the interstitial space, causing typical manifestations of HF.
Contemporary management of acute decompensated HF mainly focuses on venous decongestion via diuretic therapy. However, even if this therapy is useful, patients often develop diuretic resistance with no treatment options left
, our study aimed to evaluate the safety and technical feasibility of percutaneous transcatheter cannulation and drainage of the thoracic duct in patients with chronic HF and fluid overload.
CASE REPORT
Patient description
A 65-year-old woman, with a history of mitral valve replacement five years before and numerous episodes of HF with preserved ejection fraction, was referred to our center for persisting dyspnea (New York Heart Association (NYHA) class III) and congestion, despite high dose of furosemide (250mg twice a day) and guideline directed medical therapy including an SGLT2 inhibitor. Transthoracic echocardiography revealed increased gradients on the mitral bioprosthesis (mean: 10 mmHg, similar to the postoperative period), preserved left ventricular ejection fraction, and moderate to severe tricuspid regurgitation with moderately impaired right ventricular function. Considering the severity of the symptomatology with no other therapeutic options, the medical team proposed she participate in this protocol. The study was approved by the Ethics Committee of the center, and signed informed consent was obtained before the procedure.
Study Procedure
The intervention was performed under conscious sedation using fluoroscopic guidance. The first step of the procedure consisted of an intranodal lymphangiography (figure 1, panel 1). This was performed with an ultrasound-guided superficial bilateral inguinal node puncture using a 22-gauge spinal needle. After successful node puncture, a slow infusion (6 cc/h) of Lipiodol® (ethiodized oil) through the needle led to a successful visualization of the lymphatic system and the thoracic duct (figure 1, panel B). The humeral vein was then canulated using a micro puncture kit followed by the insertion of 5-Fr Soft-Vu Navigate 3 angiographic catheter (Sos Omni Selective; Angiodynamics, Queensbury, NY). The thoracic duct was canulated and crossed without puncture using a 2.8-Fr Progreat microcatheter (Terumo; Somerset, New Jersey, USA) and a 45° angled 0.018’’ GT Glidewire (Terumo; Somerset, New Jersey, USA). The Glidewire was exchanged for a SV-5 300cm steerable guidewire (Cordis corp., Miami Lakes, Florida) and a 4-Fr 90 cm Flexor Checkflo (Cook Medical Inc., Bloomington, IN) introducer was introduced in the canal duct (figure 1, panel C).
Figure 1Description of the percutaneous lymph drainage of thoracic duct. Panel A: Intranodal lymphangiography after bilateral inguinal node puncture using a 22-gauge spinal needle. Panel B: Visualization of the thoracic duct. Panel C: Successful introduction of a 4-Fr introducer in the canal duct. Panel D: Lymph collection
The day of the procedure, physical examination showed the presence of moderate peripheral oedema with no ascites, and jugular venous pressure was estimated at 8 cm of water. A right catheterization examination showed a mean central venous pressure of 5 mmHg, mean pulmonary arterial pressure of 35mmHg, and a cardiac index of 2.2 L/min/m2. After canulation, a waveform pressure curve in the canal duct was observed/analyzed with a mean value of 80 mmHg (simultaneous mean systemic pressure of 70 mmHg). Given the observed pressures, the lymph was collected only by gravity drainage. After 24 hours, 1,5L of lymph were retrieved (figure 1, panel D). The right catheterization before discharge showed a decrease in pulmonary arterial pressure (mean: 15 mmHg) and similar central venous pressure. Diuresis was maintained (1,6L during the first 24 hours) but diuretics were lowered before discharge to avoid hypovolemia. The canal duct pressures were re-measured before removal of the drain and were much lower (mean: 10 mmHg) than before drainage. Peripheral oedemas were less significant and jugular venous pressure was similar. The patient was discharged without any complication 48 hours after the procedure. Laboratory measurements before, during, after drainage and one month later are presented in table 1. No relevant or concerning variation of measured parameters was observed confirming the safety of lymph removal. The N-terminal pro-B type natriuretic peptide (NT-pro-BNP) value at 8 hours was 1064 ng/L and decreased to 548 ng/L two days after the procedure. The weight also decreased from 44.5 kg to 42.9 kg. This decrease was transient since one month after the procedure, the NT-pro-BNP levels and weight were similar to baseline. One month later patient quality of life assessed by the Kansas City Cardiomyopathy Questionnaire improved (34 points to 41 points) but NYHA class remained unchanged.
Table 1Laboratory measurement before, during and after drainage of the lymphatic duct
Variable
Pre-procedure
8 hours after procedure
Day-1
Day-2
One month
Normal value or Range
Weight (kg)
44.5
42.9
47.3
Sodium (mmol/L)
132
137
134
131
137
135-145
Potassium (mmol/L)
3.1
4.0
4.2
5.5
3.7
3.3-5.3
Urea (mmol/L)
5.9
9.4
11.5
8.6
3.9
1.7-8.5
Creatinine (mol/L)
59
65
68
57
45
40-90
NT-pro-BNP (ng/L)
686
1064
733
548
819
<285
Calcium (mmol/L)
2.16
2.35
2.32
N/A
N/A
2.11-255
Albumin (g/L)
31
31
26
N/A
N/A
35-50
Protein total (g/L)
67
69
65
N/A
N/A
65-82
Hemoglobin (g/L)
128
158
154
124
115
120-160
Hematocrit
0.392
0.501
0.490
0.397
0.364
0.370-0.470
Platelets (G/L)
205
244
222
172
244
160-400
White cells (G/L)
10.10
17
14.20
11.80
9.40
4.80-10.80
Lymphocytes (G/L)
1.4
0.6
1.4
0.8
N/A
Neutrophiles (G/L)
7.7
15.30
11.6
9.9
N/A
Eosinophiles (G/L)
0.007
0.0001
0.001
0.2
N/A
IgA (g/L)
1.13
1.42
1.28
N/A
N/A
0.60-4.00
IgE (K/UI/L)
908
1100
997
N/A
N/A
<100
IgG (g/L)
8.64
10.19
8.38
N/A
N/A
7.00-16.00
NT-pro BNP : N-terminal pro-B type natriuretic peptide
Heart failure is a syndrome characterized by high mortality, frequent hospitalization, and reduced quality of life. Neuro-hormonal therapeutic agents and implantable devices are widely used to prevent HF hospitalization, reduce symptoms and lower mortality. However, management of chronic and acute HF congestion is mainly limited to diuretic therapy. This work highlights for the first time the feasibility of a new strategy to treat HF congestion: percutaneous canulation and drainage of the lymph from the thoracic duct.
Two mechanisms are involved in the transport mechanism of lymph: intrinsic pumping (passive stretching and active contraction of smooth muscle cells combined with the action of the unidirectional valves composing the collecting lymphatics) and extrinsic pumping (pressure resulting from surrounding tissues, vessels and breathing). Namely, lymphatic pumping is a dynamic and highly regulated process whose failure can led to interstitial oedema. Lymph circulation deregulation in HF can be related to two factors: an impairment of lymph vessel integrity, and a reduction in lymph drainage related to high central venous pressure.
The hemodynamic stress of HF is known to be associated with systemic inflammation. Inflammation increases vascular permeability, and the leak of proteins in the interstitial space subsequently increases interstitial oncotic pressure. Consequently, there is an interstitial fluid accumulation necessitating an enhanced lymph flow. However, lymph transport also decreases in chronic inflammation (related to impaired vessel integrity and compliance) leading to maintained venous congestion.
High central venous pressure can also reduce the ability of the lymph to pour out into the venous circulation. Interestingly, the patient’s pressures measured in the canal duct were high (mean 80 mmHg) and higher than the systemic pressures. This phenomenon may be related to the capacity of the lymph vasculature to increase lymph vessel contractility when outflow resistance occurs. Nevertheless, all these factors are hypothesis generating.
This approach might play a role in congestive patients resistant to diuretics because of renal impairment or patients with consequent peripheral oedema and normovolemia related to an increase of vascular permeability.
This intervention appears to be safe and the technique is relatively similar to the access used to manage thoracic duct leakage. Nevertheless, some aspects of the procedure need to be improved. First, the intranodal lymphangiography requires the patient to lie down for approximately one hour, which may not be possible in HF patients with orthopnea. Targeting axillary instead of inguinal lymph nodes may be a promising option. Secondly, lymphatic valvules are difficult to cross and canulation of the canal duct may be challenging. Third, it is difficult to determine the quantity of lymph that needs to be collected and the potential impact of this retrieval on the immune system. An animal study using a dedicated device to enhance lymph flow without withdrawing any fluid has been recently published and illustrates other alternatives in this field
. Finally, Albumin and other plasma proteins were slightly affected by the drainage in this patient, but this one case study cannot allow us to draw any conclusion about the potential arm of this loss. It is important to underline that the hemodynamic results of the procedure seemed transient since the biomarkers and weight raised at 1-month follow-up. Therefore, this procedure might be only suitable for bailout congestive states with no other issues. Moreover, the results of this single case study should be interpreted with caution; further cases and studies are warranted to draw definitive conclusions.
CONCLUSION
In conclusion, transcatheter percutaneous drainage of lymph appears to be a feasible and promising technique to improve congestion and interstitial oedema in HF patients.
NOVEL TEACHING POINTS:
This study aimed to evaluate the feasibility and safety of percutaneous cannulation and drainage of the lymphatic canal duct to treat venous congestion of patients with chronic heart failure.
This strategy was safe and improved biologic markers shortly after the procedure.
Further studies are warranted to confirm this interesting new path.
REFERENCES
Fudim M.
Salah H.M.
Sathananthan J.
Bernier M.
Pabon-Ramos W.
Schwartz R.S.
Rodés-Cabau J.
Côté F.
Khalifa A.
Virani S.A.
Patel M.R.
Lymphatic Dysregulation in Patients With Heart Failure: JACC Review Topic of the Week.
Data availability: The data that support the findings of this study are available from the corresponding author, upon reasonable request.
Fundingsources: This study was funded by NXT Biomedical
Disclosures: The authors have nothing to disclose related to this content.
Ethics and patient approval statement: The study was approved by the Ethics Committee of the center, and signed informed consent was obtained before the procedure.
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