Congestion and Inflammation in Heart Failure: Beyond the Chicken or the Egg.

Congestion represents a prevalent yet deleterious pathophysiologic state of heart failure (HF) across the spectrum of disease stages or etiologies. While it was once simply described as the buildup of fluid in the intravascular compartment or interstitial space, the contemporary understanding of congestion has evolved. It encompasses elevated filling pressures that are unrelated to excessive volume (i.e. pressure-volume discordance) and abnormal fluid distribution, primarily arising from reduced venous capacitance [ [1] Fudim M Hernandez AF Felker GM. Role of Volume Redistribution in the Congestion of Heart Failure. Journal of the American Heart Association. 2017; 6e006817 Crossref Scopus (124) Google Scholar ]. Congestion not only contributes to the clinical manifestation HF but also plays a substantial role in the disease progression. At the level of the heart, an increase in central venous pressure impedes cardiac lymphatic return and subsequently causes myocardial edema [ [2] Brakenhielm E Alitalo K. Cardiac lymphatics in health and disease. Nature Reviews Cardiology. 2019; 16: 56-68 Crossref PubMed Scopus (97) Google Scholar ]. Acute and chronic myocardial edema lead to decreased ventricular compliance, increase coronary vascular resistance, and decrease systolic performance in animal models [ [3] Rubboli A Sobotka PA Euler DE. Effect of acute edema on left ventricular function and coronary vascular resistance in the isolated rat heart. American Journal of Physiology-Heart and Circulatory Physiology. 1994; 267: H1054-H1H61 Crossref PubMed Google Scholar , [4] Desai KV Laine GA Stewart RH Charles S. Cox J Quick CM Allen SJ Fischer UM Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema. American Journal of Physiology-Heart and Circulatory Physiology. 2008; 294: H2428-H2H34 Crossref PubMed Scopus (77) Google Scholar ]. Abdominal congestion from backward failure could lead to splanchnic venous congestion and interstitial edema that are self-perpetuating through sympathetic-induced reduction in splanchnic venous capacitance, increased intraabdominal pressure, decreased visceral lymphatic drainage, and decreased fluid clearance from renal dysfunction [ [5] Verbrugge FH Dupont M Steels P Grieten L Malbrain M Tang WH Mullens W. Abdominal contributions to cardiorenal dysfunction in congestive heart failure. J Am Coll Cardiol. 2013; 62: 485-495 Crossref PubMed Scopus (253) Google Scholar ]. The presence of tissue congestion at the periphery on routine clinical examination such as leg edema also carries independent prognostic value [ [6] Selvaraj S Claggett B Pozzi A McMurray JJV Jhund PS Packer M et al. Prognostic Implications of Congestion on Physical Examination Among Contemporary Patients With Heart Failure and Reduced Ejection Fraction. Circulation. 2019; 140: 1369-1379 Crossref PubMed Scopus (67) Google Scholar ]. However, the mechanistic insights into regional adaptation and its contribution to HF progression are limited. Veraprapas Kittipibul. Marat Fudim. Paul A. Sobotka. Experimentally Induced Peripheral Venous Congestion Exacerbates Inflammation, Oxidative Stress, and Neurohormonal and Endothelial Cell Activation in Patients With Systolic Heart FailureJournal of Cardiac FailurePreviewFluid retention and venous congestion (VC) are clinical manifestations of advanced and acute decompensated heart failure (HF) requiring hospitalization. Although representing the effect rather than the cause, VC may play an important role in the pathophysiology of HF progression. Prior HF studies reported associations between VC severity and elevation in biomarkers of inflammation, oxidative stress and neurohormonal and endothelial cell (EC) activation.1-4 However, these studies were observational, limiting causal inference. Full-Text PDF