Publish in this journal
Journal Information
Vol. 63. Issue 1.
Pages 5-8 (January 2010)
DOI: 10.1016/S1885-5857(10)70002-5
Full text access
The Active Role of Venous Congestion in the Pathophysiology of Acute Decompensated Heart Failure
Papel activo de la congestión venosa en la fisiopatología de la insuficiencia cardiaca aguda descompensada
Visits
...
Paolo C. Colomboa, Ulrich P. Jordea
a Department of Medicine, Division of Cardiology, Columbia University, New York, USA
This item has received
...
Visits
(Daily data update)
Article information
Full Text
Bibliography
Download PDF
Statistics
Figures (1)
Full Text

Chronic heart failure (CHF) hospitalizations continue to grow in Europe and the United States. It is estimated that hospitalizations for acute decompensated heart failure (ADHF) account for >75% of the health care costs for CHF patients.1,2 Data from large trials and registries have shown that most hospitalizations for ADHF occur because of symptoms (dyspnoea, abdominal bloating, and fatigue) and signs (pulmonary rales, jugular vein distension, and peripheral edema) of venous congestion rather than of low cardiac output.3,4 Symptoms of congestion typically worsen a few days (3 [2.5] days) before hospital admission.5 However, recent studies have shown that the onset of venous congestion occurs well before symptoms of congestion become apparent. Home monitoring of daily weight,6 and continuous monitoring of intracardiac pressures (Chronicle, Medtronic Inc.),7 and pulmonary congestion via intrathoracic impedance, (OptiVol, Medtronic Inc.),5 all provide evidence that venous congestion begins to occur much earlier than previously thought in the time course of ADHF.

Venous congestion (marked by an increase in weight, right side filling pressures, and accumulation of intrathoracic fluid) starts to increase at least 7- 14 days before CHF signs and symptoms worsen, eventually requiring urgent intravenous therapy.5-7 Although congestion is an important target of treatment, physicians do not do a very good job in treating congestion, as evidenced by the fact that ≈50% of patients do not lose body weight during hospitalization.8 This treatment failure has major consequences, as refractory systemic congestion is an important hemodynamic predictor of worsening renal function, rehospitalization and post-discharge mortality in patients hospitalized for ADHF.9-13

Dietary indiscretion, medication noncompliance, ischemia, arrhythmias, and worsening hypertension and left and/or right ventricular systolic or diastolic function may all promote fluid retention and venous congestion in patients with CHF.14 However, while fluid accumulation represents the effect rather than the cause, once initiated and sustained, it exercises negative effects on the heart (eg, by promoting subendocardial ischemia),15 on the kidneys (eg, by reducing perfusion pressure and causing sodium retention),12,13,16 and also, based on our initial observations, on the venous endothelium and on the peripheral production and release of cytokines and neurohormones.17,18

Our hypothesis is that venous congestion itself is a fundamental inflammatory and hemodynamic stimulus that contributes to the development and progression of ADHF through endothelial, neurohormonal, renal, and cardiac mechanisms. The discussion that follows will detail the evidence supporting this hypothesis.

The venous endothelium is the largest endocrine/ paracrine organ of the body and a key regulator of central blood volume, organ perfusion and haemostasis in CHF through transitions between quiescent and activated states that occur in response to environmental stressors such as vascular stretch associated with venous congestion.19 Using a novel approach that involves sampling of venous endothelial cells and quantification of protein and mRNA expression, we have previously reported an increase in pro-oxidant free radicals and pro-inflammatory proteins in venous endothelial cells collected from patients hospitalized for ADHF with clinical evidence of fluid overload.20,21 This venous endothelial activation partially subsides with diuresis and clinical improvement during the index hospitalisation.21 More recent animal and human data confirmed that venous congestion itself can switch the synthetic and endocrine profile of the endothelium, from quiescent toward an activated state that is pro-oxidant, pro-inflammatory and vasoconstricting in a manner consistent with that seen in patients with ADHF.17,18 The resulting peripheral release of vasoactive and pro-inflammatory neurohormones (ie, tissue necrosis factor-a, endothelin-1, interleukin-6, and angiotensin II), from the stretched endothelium and from the perivascular congested tissue, may offset the physiological adaptations that sustain the compensated state of CHF (ie, redistribution of limited cardiac output to vital organs such as the kidneys, heart, and brain). These pathophysiological events may promote additional fluid retention, and leading to a vicious cycle that can eventually result in overt decompensation.

From a renal standpoint, an increase in venous congestion and pressure has both hemodynamic and intrinsic detrimental consequences on the kidneys as it reduces organ perfusion and increases Na retention.16 Of note, both pro-oxidant free radicals and pro-inflammatory cytokines such as tissue necrosis factor-a, which are released by the stretch endothelium in response to venous congestion, have been shown to reduce renal sodium excretion.22,23

Venous congestion may also negatively impact cardiac function by causing subendocardial ischemia, left ventricular remodelling, impairment of cardiac venous drainage from coronary veins, and a lower threshold for arrhythmias.15 The resulting decrease in cardiac output may further impair renal perfusion and function, thereby causing additional fluid retention. Of note, the cardiac endocardium is structurally identical to and in continuity with the vascular endothelium, and is likely to be activated and possibly contributes to the release of angiotensin II that occurs in response to elevated cardiac filling pressures.24

Figure 1 summarizes what we consider as a "unifying peripheral venocentric hypothesis" for the pathophysiology of ADHF. At the beginning there is an insult, that causes fluid retention maybe multiple ones, of varying etiology (eg, infections, non-compliance with diet or medications, arrhythmias, ischemia, and/or worsening hypertension). Through endothelial, neurohormonal, renal, and cardiac mechanisms, venous congestion itself may lead to additional sodium and water retention. Vascular stretch associated with venous congestion may switch the synthetic and endocrine profile of the venous endothelium, from quiescent toward an activated pro-oxidant, pro-inflammatory and vasoconstricting state that, in turn, promotes peripheral release of vasoactive and pro-inflammatory neurohormones. In the kidneys, vascular congestion and activation of the stretched endothelium, now itself a source of oxidative stress and pro-inflammatory cytokines, may cause additional fluid retention. In the heart, high filling pressure further impairs systolic and diastolic function. Subsequently, when the initial insult(s) subside(s), it may be too late: the vicious cycles that link venous congestion to progressive fluid retention are already in place. Symptoms will eventually worsen after weeks of progressive fluid accumulation, eventually leading to hospitalization for overt decompensation.

Figure 1. Impact of venous congestion on the pathophysiology and treatment of acute decompensated heart failure (ADHF).

Early detection (eg, by continuous monitoring of intracardiac pressures and intrathoracic impedance) and better understanding of the pathophysiology of ADHF may allow future treatment strategies to switch from the current "rescue mode" of late intravenous interventions (ie, inotropes, diuretics), to a "preventive mode" of oral interventions. This early treatment strategy may include not only diuretics but also, as one may infer from our data and test in future studies, adjuvant means such as short-term (pulse) anti-oxidant and/or anti-inflammatory treatments that may abort ADHF before the progression to overt decompensation.

In conclusion, venous congestion may act as an independent and fundamental stimulus for the development and progression of ADHF. Importantly, our "venocentric" approach to the pathophysiology of ADHF is aimed at complementing rather than replacing the more traditional "cardiocentric," "nephrocentric," "arteriocentric" views, since all systems (ie, the heart, the kidneys, the arteries, and the veins) appear involved in the events that trigger and sustain ADHF.


Disclosure: Paolo C. Colombo, MD: Medtronic Inc: Investigator-Initiated Research Grant.

Correspondence: Paolo C. Colombo, MD,
Division of Cardiology, New York-Presbyterian Hospital, Columbia University
622W 168th Street, PH 12-134, New York, NY 10032, USA
E-mail: pcc2001@columbia.edu

Bibliography
[1]
San Román Terán CM, Guijarro Merino R, Guil García M, Villar Jiménez J, Martín Pérez M, Gómez Huelgas R..
Analysis of 27,248 hospital discharges for heart failure: a study of an administrative database 1998-2002..
Rev Clin Esp, 208 (2008), pp. 281-7
[2]
Fang J, Mensah GA, Croft JB, Keenan NL..
Heart failure-related hospitalization in the U.S., 1979 to 2004..
J Am Coll Cardiol, 52 (2008), pp. 428-34
[3]
Fonarow GC, Heywood JT, Heidenreich PA, Lopatin M, Yancy CW..
Temporal trends in clinical characteristics, treatments, and outcomes for heart failure hospitalizations, 2002 to 2004: findings from Acute Decompensated Heart Failure National Registry (ADHERE)..
Am Heart J, 153 (2007), pp. 1021-8
[4]
Allen LA, Metra M, Milo-Cotter O, Filippatos G, Reisin LH, Bensimhon DR, et al..
Improvements in signs and symptoms during hospitalization for acute heart failure follow different patterns and depend on the measurement scales used: an international, prospective registry to evaluate the evolution of Measures of Disease Severity in Acute Heart Failure (MEASURE-AHF)..
J Card Fail, 14 (2008), pp. 777-84
[5]
Yu CM, Wang L, Chau E, Chan RH, Kong SL, Tang MO, et al..
Intrathoracic impedance monitoring in patients with heart failure: correlation with fluid status and feasibility of early warning preceding hospitalization..
[6]
Chaudhry SI, Wang Y, Concato J, Gill TM, Krumholz HM..
Patterns of weight change preceding hospitalization for heart failure..
Circulation, 116 (2007), pp. 1549-54
[7]
Adamson PB, Magalski A, Braunschweig F, Bohm M, Reynolds D, Steinhaus D, et al..
Ongoing right ventricular hemodynamics in heart failure: clinical value of measurements derived from an implantable monitoring system..
J Am Coll Cardiol, 41 (2003), pp. 565-71
[8]
Gheorghiade M, Zannad F, Sopko G, Klein L, Pina IL, Konstam MA, et al..
Acute heart failure syndromes: current state and framework for future research..
Circulation, 112 (2005), pp. 3958-68
[9]
Lucas C, Johnson W, Hamilton MA, Fonarow GC, Woo MA, Flavell CM, et al..
Freedom from congestion predicts good survival despite previous class IV symptoms of heart failure..
Am Heart J, 140 (2000), pp. 840-7
[10]
Gheorghiade M, Gattis WA, O''Connor CM, Adams KF, Jr..
, Elkayam U, Barbagelata A, et al. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial..
JAMA, 291 (2004), pp. 1963-71
[11]
Nohria A, Hasselblad V, Stebbins A, Pauly DF, Fonarow GC, Shah M, et al..
Cardiorenal interactions: insights from the ESCAPE trial..
J Am Coll Cardiol, 51 (2008), pp. 1268-74
[12]
Damman K, van Deursen VM, Navis G, Voors AA, van Veldhuisen DJ, Hillege HL..
Increased central venous pressure is associated with impaired renal function and mortality in a broad spectrum of patients with cardiovascular disease..
J Am Coll Cardiol, 53 (2009), pp. 582-8
[13]
Mullens W, Abrahams Z, Francis GS, Sokos G, Taylor DO, Starling RC, et al Importance of venous congestion for worsening of renal function in advanced decompensated heart failure..
J Am Coll Cardiol..
, 53 (2009), pp. 589-96
[14]
Fonarow GC, Abraham WT, Albert NM, Stough WG, Gheorghiade M, Greenberg BH, et al..
Factors identified as precipitating hospital admissions for heart failure and clinical outcomes: findings from OPTIMIZE-HF..
Arch Intern Med, 168 (2008), pp. 847-54
[15]
Gheorghiade M, De Luca L, Fonarow GC, Filippatos G, Metra M, Francis GS..
Pathophysiologic targets in the early phase of acute heart failure syndromes..
Am J Cardiol, 96 (2005), pp. 11G-17G
[16]
Firth JD, Raine AE, Ledingham JG..
Raised venous pressure: a direct cause of renal sodium retention in oedema? Lancet..
, 1 (1988), pp. 1033-5
[17]
Colombo PC, Rastogi S, Onat D, Zaca V, Gupta RC, Jorde UP, et al Activation of endothelial cells in conduit veins of dogs with heart failure and veins of normal dogs after vascular stretch by acute volume loading..
J Card Fail..
, 15 (2009), pp. 457-63
[18]
Colombo PC, Onat D, Kebschull M, Xiang JZ, Adams T, Bolli P, et al..
Acute Venous Hypertension and Congestion Coupled with Analysis of Endothelial Gene Expression Profiling and Circulating Neurohormons: a New Model to Characterize the Endothelial and Inflammatory Response to Acute Mechanical Stress in Humans..
J Am Coll Cardiol, 53 (2009), pp. 1040-111
[19]
Gimbrone MA, Jr, Topper JN, Nagel T, Anderson KR, García-Cardena G..
Endothelial dysfunction, hemodynamic forces, and atherogenesis..
Ann N Y Acad Sci, 902 (2000), pp. 230-9
[20]
Colombo PC, Ashton AW, Celaj S, Talreja A, Banchs JE, Dubois NB, et al..
Biopsy coupled to quantitative immunofluorescence: a new method to study the human vascular endothelium..
[21]
Colombo PC, Banchs JE, Celaj S, Talreja A, Lachmann J, Malla S, et al..
Endothelial cell activation in patients with decompensated heart failure..
[22]
Garvin JL, Ortiz PA..
The role of reactive oxygen species in the regulation of tubular function..
Acta Physiol Scand, 179 (2003), pp. 225-32
[23]
DiPetrillo K, Coutermarsh B, Gesek FA..
Urinary tumor necrosis factor contributes to sodium retention and renal hypertrophy during diabetes..
Am J Physiol Renal Physiol, 284 (2003), pp. F113-121
[24]
Schrier RW, Abraham WT..
Hormones and hemodynamics in heart failure..
N Engl J Med, 341 (1999), pp. 577-85
Idiomas
Revista Española de Cardiología (English Edition)

Subscribe to our newsletter

Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.