Cardiorenal syndrome

Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology

TOPIC OUTLINE

SUMMARYDEFINITION AND CLASSIFICATIONPREVALENCEDIAGNOSISPATHOPHYSIOLOGYNeurohumoral adaptationsReduced renal perfusionIncreased renal venous pressureRight ventricular dilatation and dysfunctionSUMMARYREFERENCES

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FIGURES

CRS PathophysiologyFrank Starling curves in HFChange in sCr versus change in IAP

RELATED TOPICS

ACE inhibitors in heart failure due to systolic dysfunction: Therapeutic useAngiotensin II receptor blockers in heart failure due to systolic dysfunction: Therapeutic useAssessment of kidney functionCardiorenal syndrome: Prognosis and treatmentChronic kidney disease and coronary heart diseaseDiagnostic approach to the patient with acute kidney injury (acute renal failure) or chronic kidney diseasePathophysiology of heart failure: Left ventricular pressure-volume relationshipsPathophysiology of heart failure: Neurohumoral adaptationsUse of beta blockers in heart failure due to systolic dysfunction

Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology

Authors 
Michael S Kiernan, MD 
James E Udelson, MD, FACC 
Mark Sarnak, MD 
Marvin Konstam, MD 

Section Editor 
Stephen S Gottlieb, MD 

Deputy Editor 
Susan B Yeon, MD, JD, FACC 

Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2013. | This topic last updated: Aug 29, 2012.

DEFINITION AND CLASSIFICATION  — There are a number of important interactions between heart disease and kidney disease. The interaction is bidirectional as acute or chronic dysfunction of the heart or kidneys can induce acute or chronic dysfunction in the other organ. The clinical importance of such relationships is illustrated by the following observations:

Mortality is increased in patients with heart failure (HF) who have a reduced glomerular filtration rate (GFR). (See "Cardiorenal syndrome: Prognosis and treatment", section on 'Reduced GFR and prognosis' .)Patients with chronic kidney disease have an increased risk of both atherosclerotic cardiovascular disease and heart failure, and cardiovascular disease is responsible for up to 50 percent of deaths in patients with renal failure [ 1,2 ]. (See "Chronic kidney disease and coronary heart disease", section on 'Introduction' .)Acute or chronic systemic disorders can cause both cardiac and renal dysfunction.

The term cardiorenal syndrome (CRS) has been applied to these interactions, but the definition and classification have not been clear. A 2004 report from the National Heart, Lung, and Blood Institute defined CRS as a condition in which therapy to relieve congestive symptoms of HF is limited by a decline in renal function as manifested by a reduction in GFR [ 3 ]. The reduction in GFR was initially thought to result from a reduction in renal blood flow. However, various studies have demonstrated that cardiorenal interactions occur in both directions and in a variety of clinical settings [ 4 ]. (See 'Pathophysiology' below.)

The different interactions that can occur led to the following classification of CRS that was proposed by Ronco and colleagues [ 5 ]:

Type 1 (acute) — Acute HF results in acute kidney injury (AKI, previously called acute renal failure).Type 2 — Chronic cardiac dysfunction (eg, chronic HF) causes progressive chronic kidney disease (CKD, previously called chronic renal failure).Type 3 — Abrupt and primary worsening of kidney function due, for example, to renal ischemia or glomerulonephritis causes acute cardiac dysfunction, which may be manifested by HF.Type 4 — Primary CKD contributes to cardiac dysfunction, which may be manifested by coronary disease, HF, or arrhythmia.Type 5 (secondary) — Acute or chronic systemic disorders (eg, sepsis or diabetes mellitus) that cause both cardiac and renal dysfunction.

The prevalence of impaired renal function in patients with HF, the diagnosis of CRS, and the mechanisms by which acute HF leads to worsening kidney function (type 1 CRS) will be reviewed here. However, it may be difficult to distinguish between type 1 and type 2 CRS (chronic HF), and similar mechanisms may apply to type 2. Issues related to the prognosis and treatment of type 1 or 2 CRS are presented separately. (See "Cardiorenal syndrome: Prognosis and treatment" .)

PREVALENCE  — Heart failure (HF) is frequently accompanied by a reduction in glomerular filtration rate (GFR) via mechanisms that will be described below. (See'Pathophysiology' below.)

The prevalence of moderate to severe kidney impairment (defined as a GFR less than 60 mL/min per 1.73 m 2 ; normal more than 90 mL/min per 1.73 m 2 ) is approximately 30 to 60 percent in patients with HF [ 6-10 ]. The following observations are illustrative:

In a systematic review of 16 studies of more than 80,000 hospitalized and nonhospitalized patients with HF, moderate to severe kidney impairment (defined as an estimated GFR less than 53 mL/minute, a serum creatinine of 1.5 mg/dL [132 micromol/L] or higher, or a serum cystatin C of 1.56 mg/dL or higher) was present in 29 percent of patients [ 6 ].The Acute Decompensated Heart Failure National Registry (ADHERE) database reported data on over 100,000 patients with HF requiring hospitalization [ 9 ]. Approximately 30 percent had a diagnosis of chronic kidney disease (defined as a serum creatinine greater than 2.0 mg/dL [177 micromol/L]). The mean estimated GFR was 55 mL/min per m 2 , and only 9 percent had a normal estimated GFR (defined as greater than 90 mL/min per 1.73m 2 ) [ 10 ].

In addition to these baseline observations, patients undergoing treatment for acute or chronic HF frequently develop an increase in serum creatinine, which fulfills criteria for type 1 or type 2 CRS [ 11-20 ]. In different series, approximately 20 to 30 percent of patients developed an increase in serum creatinine of more than 0.3mg/dL (27 micromol/L) [ 11,12,14,16,18 ], and, in one report, 24 percent had an increase of 0.5 mg/dL (44 micromol/L) or more [ 14 ]. Risk factors for worsening kidney function during admission for HF include a prior history of HF or diabetes, an admission serum creatinine of 1.5 mg/dL (133 micromol/L) or higher, and uncontrolled hypertension [ 12,13,21 ]. The rise in serum creatinine usually occurs in the first three to five days of hospitalization [ 12 ].

DIAGNOSIS  — Impaired kidney function in patients with heart failure (HF) is defined as a reduction in glomerular filtration rate (GFR). The most common test used to estimate GFR is the serum creatinine concentration. However, older and sicker patients often have a reduction in muscle mass and therefore in creatinine production. Thus, the GFR may be substantially reduced in patients who have a serum creatinine that is in the normal range or only mildly elevated. Estimation equations are available that provide a better estimate of GFR than the serum creatinine alone by including known variables that affect the serum creatinine independent of GFR (eg, age, weight, sex). Another alternative to serum creatinine is measurement of serum cystatin C, which is an endogenous proteinase inhibitor synthesized and released into plasma at a constant rate by all nucleated cells. All of these tests require that the serum creatinine or cystatin C concentration be stable ; they cannot be used to estimate GFR in a patient who has a rising serum creatinine. These issues are discussed in detail elsewhere. (See "Assessment of kidney function" .)  

Among patients with HF who have an elevated serum creatinine and/or a reduced estimated GFR, it is important to distinguish between underlying kidney disease and impaired kidney function due to the cardiorenal syndrome (CRS). This distinction may be difficult and some patients have both underlying chronic kidney disease and CRS.

Findings suggestive of underlying kidney disease include significant proteinuria (usually more than 1000 mg/day), an active urine sediment with hematuria with or without pyuria or cellular casts, and/or small kidneys on radiologic evaluation. However, a normal urinalysis, which is typically present in CRS without underlying kidney disease, can also be seen in variety of renal diseases including nephrosclerosis and obstructive nephropathy. (See "Diagnostic approach to the patient with acute kidney injury (acute renal failure) or chronic kidney disease", section on 'Urinary findings' .)

Measurement of the urine sodium concentration also may be helpful. A urine sodium concentration below 25 meq/L would be expected with HF, since renal perfusion is reduced with associated activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, both of which promote sodium retention. However, higher values may be seen with concurrent diuretic therapy if the measurement is made while the diuretic is still acting. (See "Diagnostic approach to the patient with acute kidney injury (acute renal failure) or chronic kidney disease", section on 'Urine sodium excretion' .)

PATHOPHYSIOLOGY  — A variety of factors can contribute to a reduction in glomerular filtration rate (GFR) in patients with heart failure (HF) [ 4,16,22,23 ] ( figure 1 ). The major mechanisms that have been evaluated include neurohumoral adaptations, reduced renal perfusion, increased renal venous pressure, and right ventricular dysfunction.

Neurohumoral adaptations  — Impaired left ventricular function leads to a number of hemodynamic derangements, including reduced stroke volume and cardiac output, arterial underfilling, elevated atrial pressures and venous congestion [ 24 ]. These hemodynamic derangements trigger a variety of compensatory neurohormonal adaptations including activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and increases in the release of vasopressin (antidiuretic hormone), and endothelin-1 which promote salt and water retention and systemic vasoconstriction. These adaptations overwhelm the vasodilatory and natriuretic effects of natriuretic peptides, nitric oxide, prostaglandins, and bradykinin [ 20,22,25 ].

Neurohumoral adaptations can contribute to preservation of perfusion to vital organs (the brain and heart) by maintenance of systemic pressure via arterial vasoconstriction in other circulations, including the renal circulation, and by increasing myocardial contractility and heart rate. However, systemic vasoconstriction increases cardiac afterload, which reduces cardiac output, which can further reduce renal perfusion. The maladaptive nature of these adaptations is evidenced by the slowing of disease progression and reduction in mortality with the administration of angiotensin inhibitors and beta blockers in patients with HF due to systolic dysfunction. These issues are discussed in detail elsewhere. (See "Pathophysiology of heart failure: Neurohumoral adaptations" and "ACE inhibitors in heart failure due to systolic dysfunction: Therapeutic use" and "Angiotensin II receptor blockers in heart failure due to systolic dysfunction: Therapeutic use" and "Use of beta blockers in heart failure due to systolic dysfunction" .)

Reduced renal perfusion  — As mentioned above, an original definition described the cardiorenal syndrome (CRS) as a disorder in which therapy to relieve congestive symptoms of HF (eg, loop diuretics) is limited by a reduction in glomerular filtration rate (GFR); the fall in GFR was thought to result from a decline in cardiac output of as much as 20 percent due to the reduction in ventricular preload [ 3,26 ]. A similar reduction in renal perfusion may be induced by acute decompensated HF prior to treatment. However, some patients initially have little or no reduction in cardiac output with loop diuretic therapy because they are on the flat part of the Frank-Starling curve in which changes in left ventricular end-diastolic pressure have little or no effect on cardiac performance ( figure 2 ), while others have an increase in GFR following diuretic therapy that may be mediated by a reduction in renal venous pressure and/or right ventricular dilatation. (See "Pathophysiology of heart failure: Left ventricular pressure-volume relationships", section on 'Pressure-volume relationships in heart failure' and 'Increased renal venous pressure' below and 'Right ventricular dilatation and dysfunction' below.)

However, worsening kidney function in patients with HF is not solely due to reduced renal perfusion induced by a low cardiac output, as illustrated by the following observations:

The ESCAPE trial evaluated the effectiveness of pulmonary artery catheterization in 433 patients with acute decompensated HF [ 27 ]. There was no correlation between the cardiac index and either the baseline GFR or worsening kidney function, and increasing the cardiac index did not improve renal function after discharge. Similar findings were noted in another report in which HF patients with worsening kidney function did not have lower cardiac outputs or filling pressures than those without worsening kidney function [ 15 ].It has been suggested that, although reductions in cardiac index lead to a reduction in renal blood flow, the GFR is initially maintained by an increase in the fraction of renal plasma flow that is filtered (ie, the filtration fraction) [ 28 ]. In this study, the GFR was similar in patients with a cardiac index of more than 2.0 and 1.5 to 2.0 L/min per m2 (respective filtration fractions 24 and 35 percent) but substantially reduced in patients with a cardiac index below 1.5 L/min per m2 (38 versus 62 and 67 mL/min per 1.73 m2).

In addition, hypotension, which can reduce the GFR independent of renal blood flow, is an uncommon finding in patients hospitalized for acute decompensated HF. In the ADHERE registry of over 100,000 such patients, 50 percent had a systolic blood pressure of 140 mmHg or higher, while less than 2 percent had a systolic blood pressure below 90 mm/Hg [ 9 ].

Increased renal venous pressure  — Both animal and human studies have shown that increasing intraabdominal or central venous pressure, which should also increase renal venous pressure, reduce the glomerular filtration rate (GFR) [ 4,29 ]. In an initial study in 17 normal adults, for example, raising the intraabdominal venous pressure to about 20 mmHg led to average reductions in renal plasma flow and GFR of 24 and 28 percent, respectively [ 30 ]. An adverse impact of venous congestion on kidney function has also been described in animal models as manifested by a reduction in GFR [ 31-34 ] and sodium retention [ 31,35,36 ].  

Subsequent studies in patients with HF demonstrated an inverse relationship between venous pressure and GFR when the central venous pressure was measured directly [ 37-39 ] or elevated jugular venous pressure was diagnosed on physical examination [ 40 ]:

In one report, 58 of 145 patients (40 percent) hospitalized for acute decompensated HF developed worsening kidney function, defined as an increase in serum creatinine of at least 0.3 mg/dL (27 micromol/L) [ 37 ]. These patients had a significantly higher central venous pressure (CVP) than those with stable renal function (18 versus 12 mmHg) and the frequency of worsening kidney function was lowest in patients with a CVP less than 8 mmHg. The predictive value of CVP was independent of systemic blood pressure, pulmonary capillary wedge pressure, cardiac index, and estimated GFR. In contrast to the importance of CVP, the cardiac index on admission and an improvement in cardiac index with therapy had a limited impact on the frequency of worsening kidney function.Similar findings were noted in another study in which a higher CVP was also associated with a significant increase in mortality at a median follow-up of more than 10 years (hazard ratio 1.03 per 1 mmHg increase in CVP) [ 38 ].In a series of 40 consecutive patients with acute decompensated HF, 24 had an elevation in intraabdominal venous pressure (IAVP) which was defined as 8 mmHg or higher [ 39 ]. At baseline, these patients, compared with those with a normal IAVP, had a significantly higher serum creatinine (mean 2.3 versus 1.5mg/dL [203 versus 133 micromol/L]) and a significantly lower estimated GFR (mean 40 versus 63 mL/min). In addition, there was a strong correlation between the degree of reduction in IAVP with therapy and improvement in GFR that did not correlate with any other hemodynamic variable ( figure 3 ).

Increases in renal venous pressure may also contribute to the association between the degree of tricuspid regurgitation (TR) and worsening kidney function. In a review of 196 patients with TR, those with at least moderate TR had a lower estimated GFR [ 41 ]. In addition, there was a linear relationship between the severity of TR and the magnitude of impairment in GFR.

The mechanisms by which increased renal venous pressure might lead to a reduction in GFR are not well understood [ 16,29 ].

Right ventricular dilatation and dysfunction  — Right ventricular (RV) dilatation and dysfunction may adversely affect kidney function through at least two mechanisms:

The associated elevation in central venous pressure elevation can lower the GFR as discussed in the preceding section.RV dilatation impairs left ventricular (LV) filling, and therefore forward output, via a ventricular interdependent effect (also known as the reverse Bernheim phenomenon) [ 42 ]. Increased pressure within a distended right ventricle increases LV extramural pressure, reducing LV transmural pressure for any given intracavitary LV pressure and inducing leftward interventricular septal bowing, thereby diminishing LV preload and distensibility and reducing forward flow [43,44 ]. An intact pericardium plays a role in ventricular interaction, but experimental observations suggest that the pericardium is not critical to the interaction [ 45 ].

Thus, a reduction in RV filling pressure during treatment of HF may lead to an increase in GFR, both by reducing renal venous pressure and by diminishing ventricular interdependent impairment of left ventricular filling [ 46 ].

SUMMARY

Acute or chronic dysfunction of the heart or kidneys can induce acute or chronic dysfunction in the other organ. In addition, both heart and kidney function can be impaired by an acute or chronic systemic disorder. The term cardiorenal syndrome (CRS) has been applied to these interactions. In type 1 CRS, acute heart failure (HF) leads to worsening kidney function. In type 2 CRS, chronic HF causes progressive chronic kidney disease. (See 'Definition and classification'above.)The prevalence of moderate to severe kidney impairment (defined as a glomerular filtration rate [GFR] less than 60 mL/min per 1.73 m2) is approximately 30 to 40 percent in patients with HF. In addition to these baseline observations, patients undergoing treatment for acute or chronic HF frequently develop an increase in serum creatinine, which fulfills criteria for type 1 or type 2 CRS. (See 'Prevalence' above.)Among patients with HF who have an elevated serum creatinine and/or a reduced estimated GFR, it is important to distinguish between underlying kidney disease and impaired kidney function due to the CRS. (See 'Diagnosis' above.)A variety of factors can contribute to a reduction in GFR in patients with HF. The major mechanisms that have been evaluated include neurohumoral adaptations, reduced renal perfusion, increased renal venous pressure, and right ventricular dysfunction. (See 'Pathophysiology' above.)

REFERENCESUnited States Renal Data System: Excerpts from the USRDS 2007 annual data report: atlas of end-stage renal disease in the United States. Minneapolis, MN 2007.Coresh J, Astor BC, Greene T, et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003; 41:1.file://www.nhlbi.nih.gov/meetings/workshops/cardiorenal-hf-hd.htm (Accessed on September 01, 2010).Bock JS, Gottlieb SS. Cardiorenal syndrome: new perspectives. Circulation 2010; 121:2592.Ronco C, Haapio M, House AA, et al. Cardiorenal syndrome. J Am Coll Cardiol 2008; 52:1527.Smith GL, Lichtman JH, Bracken MB, et al. Renal impairment and outcomes in heart failure: systematic review and meta-analysis. J Am Coll Cardiol 2006; 47:1987.Ezekowitz J, McAlister FA, Humphries KH, et al. The association among renal insufficiency, pharmacotherapy, and outcomes in 6,427 patients with heart failure and coronary artery disease. J Am Coll Cardiol 2004; 44:1587.Hillege HL, Girbes AR, de Kam PJ, et al. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation 2000; 102:203.Adams KF Jr, Fonarow GC, Emerman CL, et al. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 2005; 149:209.Heywood JT, Fonarow GC, Costanzo MR, et al. High prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated heart failure: a report from the ADHERE database. J Card Fail 2007; 13:422.Owan TE, Hodge DO, Herges RM, et al. Secular trends in renal dysfunction and outcomes in hospitalized heart failure patients. J Card Fail 2006; 12:257.Forman DE, Butler J, Wang Y, et al. Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol 2004; 43:61.Krumholz HM, Chen YT, Vaccarino V, et al. Correlates and impact on outcomes of worsening renal function in patients > or =65 years of age with heart failure. Am J Cardiol 2000; 85:1110.Smith GL, Vaccarino V, Kosiborod M, et al. Worsening renal function: what is a clinically meaningful change in creatinine during hospitalization with heart failure? J Card Fail 2003; 9:13.Weinfeld MS, Chertow GM, Stevenson LW. Aggravated renal dysfunction during intensive therapy for advanced chronic heart failure. Am Heart J 1999; 138:285.Shamseddin MK, Parfrey PS. Mechanisms of the cardiorenal syndromes. Nat Rev Nephrol 2009; 5:641.Cowie MR, Komajda M, Murray-Thomas T, et al. Prevalence and impact of worsening renal function in patients hospitalized with decompensated heart failure: results of the prospective outcomes study in heart failure (POSH). Eur Heart J 2006; 27:1216.Damman K, Navis G, Voors AA, et al. Worsening renal function and prognosis in heart failure: systematic review and meta-analysis. J Card Fail 2007; 13:599.Gottlieb SS, Abraham W, Butler J, et al. The prognostic importance of different definitions of worsening renal function in congestive heart failure. J Card Fail 2002; 8:136.Logeart D, Tabet JY, Hittinger L, et al. Transient worsening of renal function during hospitalization for acute heart failure alters outcome. Int J Cardiol 2008; 127:228.Butler J, Forman DE, Abraham WT, et al. Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. Am Heart J 2004; 147:331.Sarraf M, Masoumi A, Schrier RW. Cardiorenal syndrome in acute decompensated heart failure. Clin J Am Soc Nephrol 2009; 4:2013.Liang KV, Williams AW, Greene EL, Redfield MM. Acute decompensated heart failure and the cardiorenal syndrome. Crit Care Med 2008; 36:S75.Schrier RW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med 1999; 341:577.Cadnapaphornchai MA, Gurevich AK, Weinberger HD, Schrier RW. Pathophysiology of sodium and water retention in heart failure. Cardiology 2001; 96:122.Stampfer M, Epstein SE, Beiser GD, Braunwald E. Hemodynamic effects of diuresis at rest and during intense upright exercise in patients with impaired cardiac function. Circulation 1968; 37:900.Nohria A, Hasselblad V, Stebbins A, et al. Cardiorenal interactions: insights from the ESCAPE trial. J Am Coll Cardiol 2008; 51:1268.Ljungman S, Laragh JH, Cody RJ. Role of the kidney in congestive heart failure. Relationship of cardiac index to kidney function. Drugs 1990; 39 Suppl 4:10.Wencker D. Acute cardio-renal syndrome: progression from congestive heart failure to congestive kidney failure. Curr Heart Fail Rep 2007; 4:134.Bradley SE, Bradley GP. THE EFFECT OF INCREASED INTRA-ABDOMINAL PRESSURE ON RENAL FUNCTION IN MAN. J Clin Invest 1947; 26:1010.BLAKE WD, WEGRIA R. Effect of increased renal venous pressure on renal function. Am J Physiol 1949; 157:1.Burnett JC Jr, Knox FG. Renal interstitial pressure and sodium excretion during renal vein constriction. Am J Physiol 1980; 238:F279.Dilley JR, Corradi A, Arendshorst WJ. Glomerular ultrafiltration dynamics during increased renal venous pressure. Am J Physiol 1983; 244:F650.Doty JM, Saggi BH, Sugerman HJ, et al. Effect of increased renal venous pressure on renal function. J Trauma 1999; 47:1000.Firth JD, Raine AE, Ledingham JG. Raised venous pressure: a direct cause of renal sodium retention in oedema? Lancet 1988; 1:1033.Abildgaard U, Amtorp O, Holstein-Rathlou NH, et al. Effect of renal venous pressure elevation on tubular sodium and water reabsorption in the dog kidney. Acta Physiol Scand 1988; 132:135.Mullens W, Abrahams Z, Francis GS, et al. Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol 2009; 53:589.Damman K, van Deursen VM, Navis G, et al. 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 2009; 53:582.Mullens W, Abrahams Z, Skouri HN, et al. Elevated intra-abdominal pressure in acute decompensated heart failure: a potential contributor to worsening renal function? J Am Coll Cardiol 2008; 51:300.Drazner MH, Rame JE, Stevenson LW, Dries DL. Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure. N Engl J Med 2001; 345:574.Maeder MT, Holst DP, Kaye DM. Tricuspid regurgitation contributes to renal dysfunction in patients with heart failure. J Card Fail 2008; 14:824.Alpert JS. The effect of right ventricular dysfunction on left ventricular form and function. Chest 2001; 119:1632.Konstam, MA, Isner, J. The Right Ventricle, Konstam, MA, Isner, J (Eds), Kluwer Academic Publishers, 2009.Marcus JT, Vonk Noordegraaf A, Roeleveld RJ, et al. Impaired left ventricular filling due to right ventricular pressure overload in primary pulmonary hypertension: noninvasive monitoring using MRI. Chest 2001; 119:1761.Little WC, Badke FR, O'Rourke RA. Effect of right ventricular pressure on the end-diastolic left ventricular pressure-volume relationship before and after chronic right ventricular pressure overload in dogs without pericardia. Circ Res 1984; 54:719.Testani JM, Khera AV, St John Sutton MG, et al. Effect of right ventricular function and venous congestion on cardiorenal interactions during the treatment of decompensated heart failure. Am J Cardiol 2010; 105:511.

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