HomeCirculationVol. 145, No. 11Myocardial Edema Provides a Link Between Pulmonary Arterial Hypertension and Pericardial Effusion Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBMyocardial Edema Provides a Link Between Pulmonary Arterial Hypertension and Pericardial Effusion Randolph H. Stewart, DVM, PhD, Charles S. Cox Jr, MD, Steven J. Allen, MD and Glen A. Laine, PhD Randolph H. StewartRandolph H. Stewart Correspondence to: Randolph H. Stewart, DVM, PhD, Texas A&M University, 4466 TAMU, College Station, TX 77843-4466. Email E-mail Address: [email protected] https://orcid.org/0000-0002-3867-1016 Michael E. DeBakey Institute (R.H.S., C.S.C., S.J.A., G.A.L), Texas A&M University, College Station. Department of Veterinary Physiology and Pharmacology (R.H.S.), Texas A&M University, College Station. Search for more papers by this author , Charles S. Cox JrCharles S. Cox Jr Michael E. DeBakey Institute (R.H.S., C.S.C., S.J.A., G.A.L), Texas A&M University, College Station. McGovern Medical School at UTHealth, University of Texas Health Science Center at Houston (C.S.C.). Search for more papers by this author , Steven J. AllenSteven J. Allen Michael E. DeBakey Institute (R.H.S., C.S.C., S.J.A., G.A.L), Texas A&M University, College Station. Search for more papers by this author and Glen A. LaineGlen A. Laine Michael E. DeBakey Institute (R.H.S., C.S.C., S.J.A., G.A.L), Texas A&M University, College Station. Search for more papers by this author Originally published14 Mar 2022https://doi.org/10.1161/CIRCULATIONAHA.121.057666Circulation. 2022;145:793–795Pericardial effusion is a common finding in adults with pulmonary hypertension, associated with higher mean right atrial pressure and systemic venous pressures but not pulmonary artery wedge pressure.1,2 Although most pericardial effusions in pulmonary hypertension are not hemodynamically significant, both the presence and magnitude of the effusion are predictors of increased mortality.1 Experimental studies elucidating the mechanisms of myocardial fluid balance provide a convincing mechanistic link between pulmonary hypertension and pericardial effusion. In brief, an increase in pulmonary artery pressure causes myocardial interstitial edema formation, which leads to increased transudation of myocardial interstitial fluid through the epicardium into the surrounding pericardial space.Myocardial Interstitial Fluid FlowA change in myocardial interstitial fluid volume is difficult to document clinically.3 Therefore, myocardial interstitial edema is not a commonly recognized clinical disorder. However, several clinically relevant conditions and interventions result in myocardial edema formation, including pulmonary hypertension, systemic hypertension, and cardiopulmonary bypass with cardioplegic arrest.3,4 Myocardial interstitial fluid arises from ultrafiltration of plasma from coronary microvessels into the interstitial space.3 This interstitial fluid then drains into lymphatic capillaries and returns to the systemic veins by the lymphatic system. In organs like the heart located within potential spaces, interstitial fluid can also exit by serosal transudation (ie, myocardial interstitial fluid can flow through the epicardium directly into the surrounding pericardial space).5 Pericardial fluid is then drained by lymphatic vessels and returned to the blood circulation.Coronary Venous Hypertension Causes Myocardial EdemaVenous hypertension in most tissues reliably increases microvascular pressure, which increases the rate of microvascular filtration. In the heart, the majority of the coronary venous flow empties into the right atrium by the coronary sinus with some venous blood also flowing into both the right atrial and right ventricular chambers through thebesian veins. Using this phenomenon, investigators have successfully manipulated the myocardial microvascular filtration rate by altering coronary sinus pressure.3,4 Coronary sinus hypertension causes myocardial interstitial edema formation by elevating microvascular hydrostatic pressure and thus increasing myocardial microvascular filtration into the interstitial space.3,4 It is important that this edema formation occurs in the left ventricular myocardium as well as in the right.3 Myocardial edema formation results in marked increases in myocardial lymph flow.3,4 Because the lymphatic system empties into the great veins of the neck, systemic venous pressure represents the lymphatic outflow pressure.3 Laine and Allen4 demonstrated that increasing superior vena caval pressure to 20 mm Hg in anesthetized dogs reduced myocardial lymph flow to near zero. This lymph flow reduction alone did not cause a significant increase in myocardial water content. However, pairing lymph flow reduction with coronary sinus hypertension resulted in myocardial edema formation that was significantly greater than that of coronary sinus hypertension alone.4Pulmonary Hypertension Causes Myocardial EdemaExperimentally induced pulmonary arterial hypertension results in myocardial interstitial edema formation in both acute and chronic preparations.3,4 Note that these experimental studies focused on the effect of increasing pulmonary artery pressures alone on myocardial fluid balance, rather than on the broader pathogenesis of diseases characterized by pulmonary hypertension. These studies suggest the following. Pulmonary hypertension increases right atrial and right ventricular pressures that, in turn, elevate pressures within the coronary sinus and thebesian veins. This venous hypertension increases microvascular pressures within the coronary circulation and thereby increases the rate of filtration into the myocardial interstitial space leading to edema formation (Figure). In addition, the elevation of right heart pressures can also result in increased superior vena caval pressure, further exacerbating myocardial edema formation by impeding myocardial lymph flow2–4 (Figure).Download figureDownload PowerPointFigure. Schematic demonstrating the changes in myocardial and pericardial fluid balance after an increase in pulmonary artery pressure.Myocardial Edema Leads To Increased Epicardial TransudationInduction of coronary sinus hypertension leads not only to myocardial edema formation but also to increased epicardial transudation into the pericardial space.5 This occurs as a result of the edema-related increase in interstitial pressure that drives interstitial fluid through the epicardium into the pericardial space. Flow across the epicardium responds in a predictable linear fashion to changes in both the hydrostatic pressure and the colloid osmotic pressure of the pericardial fluid, driven by factors modeled in the Starling-Landis equation (ie, the hydrostatic and colloid osmotic pressures in the interstitial space and pericardial space and the fluid and protein permeabilities of the epicardium).5 In addition, lymphatic drainage of pericardial fluid is most likely diminished by increased systemic venous pressure. Supporting that premise, Chopra et al2 noted that the presence of a pericardial effusion was highly predictive of the presence of systemic venous hypertension.Clinical ConsequencesMost pericardial effusions in pulmonary hypertension are not hemodynamically significant and can be treated without pericardiocentesis, but large effusions can also occur, occasionally leading to cardiac tamponade. Atypical presentations of tamponade may also be seen, including presentations with isolated left atrial or right atrial collapse and increased respiratory variation of transmitral flow. High mortality rates have been reported in this clinical situation, likely caused by both the underlying condition and potential periprocedural complications.1 Myocardial edema may also have significant clinical consequences for the left ventricle, including increased chamber stiffness, reduced contractility, and increases in long-term collagen deposition, although the clinical significance of these findings requires further study.3In summary, current evidence strongly indicates that increases in pulmonary vascular resistance result in pericardial effusion by inducing myocardial edema formation. The increase in right atrial pressure appears to be a key change, leading to increased coronary venous and microvascular pressures as well as increased systemic venous pressures, resulting in increased filtration into the myocardial interstitial space, increased epicardial transudation, and impaired lymphatic drainage from both the myocardial interstitium and the pericardial space.Article InformationSources of FundingNone.Disclosures Dr Stewart receives consulting fees from WhiteSwell Limited, Parkmore, Galway, Ireland. The other authors report no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Sources of Funding and Disclosures, see page 795.Circulation is available at www.ahajournals.org/journal/circCorrespondence to: Randolph H. Stewart, DVM, PhD, Texas A&M University, 4466 TAMU, College Station, TX 77843-4466. Email [email protected]tamu.edu