Cardiac Lymphatic Dysfunction in Heart Failure: A New Paradigm for Congestion, Inflammation, and Therapy.

Area of Science:

• Cardiovascular Biology
• Lymphatic Physiology
• Pathophysiology of Heart Failure

Background:

• Traditional heart failure (HF) models inadequately explain persistent congestion, edema, inflammation, and fibrosis.
• These unresolved issues persist despite optimized hemodynamic, neurohormonal, and cardiorenal therapies.

Purpose of the Study:

• To review the role of the cardiac lymphatic system in HF.
• To evaluate cardiac lymphatic dysfunction as a link between congestion, inflammation, and adverse cardiac remodeling.

Main Methods:

• A narrative review based on a structured literature search (PubMed/MEDLINE) from January 2000 to April 2026.
• Emphasis on recent studies (2018 onwards) and mechanistic investigations.
• Search terms included cardiac lymphatics, heart failure, lymphangiogenesis, edema, congestion, inflammation, and specific HF phenotypes.

Main Results:

• Cardiac lymphatics clear interstitial fluid, proteins, lipids, and immune cells from the myocardium.
• Preclinical models show impaired lymphatic function promotes edema, inflammation, fibrosis, and ventricular dysfunction.
• Lymphatic restoration strategies, particularly via the VEGF-C/VEGFR-3 axis, show promise in preclinical HF models.

Conclusions:

• Cardiac lymphatic dysfunction offers a framework linking congestion and inflammation in HF.
• The cardiac lymphatic system actively influences myocardial homeostasis and HF progression.
• Recognizing lymphatic insufficiency in HF may lead to novel diagnostics and therapies, including decongestion and lymphatic repair.