The increase in heart failure (HF) prevalence and considerable burden to healthcare systems have made HF a global pandemic (1, 2). Fluid overload, the hallmark of HF, refers to a progressive body fluid retention or redistribution that impedes multiple body system functions (3). Many symptoms are associated with fluid overload symptoms, such as dyspnea, coughing, wheezing, edema, pain, or fatigue (3, 4). These symptoms are highly prevalent and burdensome, leading to poor quality of life and decreased daily living functions (4). The experience of fluid overload symptoms not only is the most commonly cited reason for HF hospital admission or readmission but also creates substantial burdens on health system, patients, and families (5, 6).

Lymphatic system plays an essential role in body fluid regulation and pathogenesis of cardiovascular diseases (7–9). The lymphatic vascular system that lies parallel to the blood vascular system maintains fluid homeostasis between intravascular and interstitial spaces by collecting fluid from the interstitial space and draining it back into the venous circulation (10–12). It is estimated that up to 8 liters of interstitial fluid are scavenged each day by the lymphatic capillaries that line all organs and are transported by the unidirectional lymphatics to the blood circulation (10). Fluid overload occurs when fluid is not drained at the same rate as it leaks into the interstitial spaces (10, 11).

Activating lymphatic system holds a great promise for reducing fluid overload as the interstitial fluid is drained exclusively by lymphatic pumping (11, 12). Exercise that stimulates muscle contraction and breathing can promote lymphatic flow, and potentially decreases fluid accumulation in tissues and interstitium (12, 13). A three- to six-fold increase in the lymph clearance rates was observed using a scintigraphic device during human active exercise compared with resting levels (14). This phenomenon was also confirmed in an animal experiment using direct cannulation of a lymphatic duct in anaesthetized sheep (15). Therefore, therapeutic exercises focusing on optimizing lymph fluid flow can be promising to prevent and manage fluid overload symptoms in HF.

This pilot study was conducted to examine the effects of exercises stimulating lymphatic system on fluid overload symptoms in HF. We hypothesized that lymphatic exercises that simulate lymphatic pumping and drainage could decrease fluid accumulation in tissues and interstitium in patients with HF, in turn, alleviate fluid overload symptoms and burden (12, 13). We have developed and extensively tested a non-pharmacological The-Optimal-Lymph-Flow (TOLF) intervention that builds patients self-management skills to promote lymph fluid flow and results in reduced pain, swelling, lymph fluid level, reverse of mild lymphedema, and improved function and quality of life in cancer patients (16–24). TOLF includes strategies to promote lymph fluid flow: therapeutic lymphatic exercises, healthy diet, and proper sleep (16–24). The essential component of TOLF is 8-minute lymphatic exercises (i.e., muscle-tightening deep breathing, muscle-tightening pumping, and large muscle exercises) designed to stimulate lymphatic system by simulating lymphatic pumping to promote lymph fluid flow (16). We conducted a pilot single-blind two-group randomized controlled trial (RCT) to evaluate the preliminary effects of 4-week TOLF lymphatic exercise training in 66 adult patients with HF.

The fundamental function of the lymphatic system in fluid homeostasis has long been overlooked, largely because of the difficulty in visualizing the transparent lymphatic vessels (8). This pilot clinical trial was the first to provide initial empirical evidence that the TOLF-HF program focusing on stimulating lymphatic system to promote fluid flow was effective in alleviating fluid overload symptoms of shortness of breath, cough, swelling of arms or legs and waking up breathless at night, decreasing abnormal weight gains, and improving physical functions for patients with HF. Recent research advances into the lymphatic network and the pathogenesis of cardiovascular diseases have made the lymphatic circulation an active target for the treatment of cardiovascular diseases (8, 9). The innovative application of TOLF-HF lymphatic exercises in patients with HF may open new avenues for nonpharmaceutical interventions for prevention and management of fluid overload in HF.

The accumulation of body fluid is an important driver of disease progression and symptom deterioration in HF (5). Worsening HF triggered by volume overload would manifest as multiple congestion symptoms including symptoms of pulmonary congestion and systemic venous congestion, causing patient distress (4, 28). We found that the 4-week TOLF-HF lymphatic exercises in addition to standard patient care was beneficial in reducing either the prevalence or burden of the majority of the fluid overload symptoms. Specifically, patients who received the intervention had 64.3% less likelihood of reporting waking up breathless at night and a trend towards less shortness of breath, cough, and swelling of arms or legs. Patients also benefited from the intervention by an alleviated symptom burden for shortness of breath, cough, and swelling of arms or legs. The symptomatic relief of trouble breathing (i.e., shortness of breath and waking up breathless at night) and coughing can be explained by the improved congestion in the pulmonary circulation while the relief of limb swelling can be explained by the improved congestion in the systemic circulation (37, 38). The core TOLF-HF intervention consists of lymphatic exercises of muscle tightening, stretching and pumping movements coordinated with deep breathing to imitate the physiological process of lymph pumping and propulsion; in addition, lymphatic exercises also induce musculoskeletal contractions, arterial pulsations, skin tensions, postural changes, and breathing alterations. Such lymphatic exercises could produce a synergistic effect to accelerate fluid volume removal not only in the thoracic area but also throughout the whole body, thus achieving positive outcomes in fluid overload symptom relief (16).

Our study found the TOLF-HF exercises did not reduce neither the prevalence nor the burden of difficulty breathing when lying flat or lack of energy. Difficulty breathing when lying flat represents the deteriorated cardiac health status and occurred more frequently in patients with more severe HF (39), while all patients recruited for this study were in chronic or stable phase and classified as NYHA class II or III. This might help explain the nonsignificant result for this symptom within our study. Lack of energy (also known as exercise intolerance or fatigue) in HF is a complex and multifactorial phenomenon; the exact pathogenesis of this symptom is not yet fully understood. On the one side, lack of energy is indicative of skeleton muscle hypoperfusion caused by interstitial fluid overload and poor cardiac output (38, 39). On the other side, lack of energy also reflects clinical factors such as aging, anemia, muscle weakness, nutritional deficiencies, sleep disorders, and psychosocial distress (40, 41). Therefore, it is reasonable that TOLF-HF exercises particularly targeting on the problem of fluid overload may not be as effective as expected in attenuating the perception of lack of energy.

Weight fluctuation is an objective and measurable indicator of fluid volume status in HF (42). Our study suggested that the TOLF-HF intervention was effective in reducing the number of abnormal weight gains. Sudden weight gain commonly means that excess fluid is building up in the body and signals the worsening of cardiac pumping capacity (42). This finding supported our hypothesis that the TOLF-HF intervention, designed to stimulate the lymphatic system to promote fluid flow, was effective to decrease or offset the water retention in the body. The TOLF-HF intervention is safe and easy to perform while patients are sitting, standing, or lying; this makes easier for patients to adhere to the lymphatic exercises. Thus, the TOLF-HF intervention holds a great promise as an adjuvant intervention for patients with HF to maintain body weight within a stable range.

In addition, physical functions are important outcomes that reflects the impact of HF on patients' functional status (35). Findings of the trial demonstrated that the TOLF-HF intervention had significantly improved physical functions for patients with HF. The positive effect can be explained by the beneficial role of TOLF-HF exercises in ameliorating fluid overload symptoms (30, 43) and the fact that the intervention prompted the patients to lead an active lifestyle. It is well-known that adopting a physically active lifestyle is one of the best ways that people can do to help prevent illness, preserve health, and enhance physical functions (44, 45).

To our knowledge, previous studies focusing on the effects of exercise intervention on fluid overload in HF were limited (46). This is a pioneer study that examined exercise-based intervention specifically targeting lymphatic system on alleviation of fluid overload symptoms by providing rigorous prospective randomized controlled data. Efficacious lymphatic transport entails the coordination of lymphatic pumping. Specifically, lymphatic contractions occur with a phase lag as the contractions propagated downstream from one lymphangion to the next generated the highest lymph flow (7, 10). The TOLF-HF exercises produced the desired effects as the intervention was designed to mimic the physiological process of lymphatic pumping (16). Apart from that, this intervention had a number of strengths. First, the TOLF-HF intervention is easy-to-learn and elderly-friendly, as such the intervention is especially appropriate for HF population. Second, the TOLF-HF intervention consists of a series of relatively low-intensity exercises and requires low physical demands. Even immobilized or bedridden patients can perform the most parts of the exercises. Finally, the TOLF-HF intervention has been shown to be feasible and acceptable to patients in this pilot trial as well as in previous experimental studies with breast cancer survivors (16–18, 24). Therefore, the TOLF-HF intervention is a pragmatic, effective, well-tolerated, and easily-integrated-into-daily-routine self-care program for the prevention and management of fluid overload and associated symptoms in patients with HF.

We recognize that there are several limitations for the current study. There were no significant between-group differences in baseline characteristics except for the number of co-morbidities, some discrepancies still existed. Because of the relatively small sample size and the exploratory nature of this study, the possibility of chance findings cannot be excluded. Additional limitations include relatively short follow-up period, inclusion of the patients who had NYHA class II or III. Multicenter studies with a larger sample size, longer follow-up, and comprising of a wider spectrum of HF cases are needed. Patient participation and compliance with the exercise protocols are critical to fully elucidate the efficacy of the intervention. In the study, nearly 90% (26/29) patients reported performing the TOLF-HF exercises twice a day as prescribed. However, lack of real-time monitoring of the truly implemented exercise dose, limiting the study's ability to explore the dose-effectiveness of the intervention. Future technology innovation should focus on wearable device to monitor the adherence to TOLF lymphatic exercises.

In conclusion, our study suggests that the TOLF-HF program focusing on promoting lymph fluid flow through the performance of therapeutic lymphatic exercises is an efficacious adjuvant therapy for patients with HF in the management of fluid overload symptoms, maintenance of stable body weight, and improvement of physical functions. Given its acceptability, practicality, safety, and effectiveness, the TOLF-HF program should be further tested as part of routine HF care. The current study represents an important initial step targeting the lymphatic system to counteract fluid accumulation and symptom exacerbations. Future research is to develop wearable devices for real-time monitor of the home-based TOLF-HF protocol, such innovation may allow detailed elucidation of the mechanisms of lymphatic system stimulation on fluid overload symptoms and body fluid level in HF.