Motivation: Ever since the week on heart failure in second year of medical school, I have been thinking about congestive heart failure (CHF) as consisting of "backup" symptoms like dyspnea and edema or "forward flow" symptoms like somnolence and fatigue. One of the CHF exacerbation symptoms that I usually categorize under forward flow is renal failure. The presumed explanation for renal failure is relative renal hypoperfusion from decreased cardiac output in acute CHF exacerbation. Recently, I learnt about some trials that challenged this view. Here is one of the trials:
Paper: Nohria, A., et. al. Cardiorenal Interactions: Insights From the ESCAPE Trial. J. Am. Coll. Cardiol.(2008) 51: 1268-74. http://content.onlinejacc.org/cgi/content/full/51/13/1268
Methods: The ESCAPE trial was a randomized trial comparing pulmonary artery catheter versus clinical volume assessment based treatment for acute heart failure exacerbation. Included patients had LVEF<30% with SBP<125 mmHg with signs and symptoms of acute heart failure. Patients with baseline creatinine >3.5 mg/dL were excluded. The current paper was an ad hoc analysis of baseline hemodynamic parameters from pulmonary artery catheter measurements and serum creatinine.
Results:
Subjects: In general, the mean age of the patient group was 56 with serum creatinine of 1.5. Most of the patients were getting an ACE-I/ARB and beta-blocker.
Hemodyamic Correlation: There was no correlation between baseline serum creatinine or estimated GFR and cardiac index, systemic vascular resistance, or wedge pressure! There was a weak but significant correlation between baseline serum creatinine and right atrial pressure (r = 0.165, p = 0.03). Similar correlation was found between baseline estimated GFR and right atrial pressure (r = -0.195, p = 0.01), meaning higher right atrial pressures were correlated with decreased GFR.
Discussion: This paper clearly calls into question the assumption that renal dysfunction from acute heart failure is directly linked to renal hypoperfusion. Renal failure seen in acute heart failure is being increasingly called the "cardiorenal syndrome" in recognition of the more complex pathophysiology. Rather than renal arterial hypoperfusion, this trial along with other evidence suggests that elevated venous pressures may directly compromise renal function. One of the problems in extrapolating from trials like this is the complexity of interacting factors. The patients in this trial were sick and being treated with multiple agents like beta-blockers and ACE-I/ARB that also affect the renal vasculature. But, these pharmacologic confounders would be expected to affect vascular tone, and no correlation was found between systemic vascular resistance and renal dysfunction either. Besides the effects of elevated venous pressure, other possible explanations for renal dysfunction include undefined direct toxic effects of therapeutic agents. Also, many processes that worsen CHF, like HTN and diabetes, also have pathologic effects on the kidneys. In the coming years, we will likely learn more about the complex pathophysiology of cardiorenal syndrome!
Paper: Nohria, A., et. al. Cardiorenal Interactions: Insights From the ESCAPE Trial. J. Am. Coll. Cardiol.(2008) 51: 1268-74. http://content.onlinejacc.org/cgi/content/full/51/13/1268
Methods: The ESCAPE trial was a randomized trial comparing pulmonary artery catheter versus clinical volume assessment based treatment for acute heart failure exacerbation. Included patients had LVEF<30% with SBP<125 mmHg with signs and symptoms of acute heart failure. Patients with baseline creatinine >3.5 mg/dL were excluded. The current paper was an ad hoc analysis of baseline hemodynamic parameters from pulmonary artery catheter measurements and serum creatinine.
Results:
Subjects: In general, the mean age of the patient group was 56 with serum creatinine of 1.5. Most of the patients were getting an ACE-I/ARB and beta-blocker.
Hemodyamic Correlation: There was no correlation between baseline serum creatinine or estimated GFR and cardiac index, systemic vascular resistance, or wedge pressure! There was a weak but significant correlation between baseline serum creatinine and right atrial pressure (r = 0.165, p = 0.03). Similar correlation was found between baseline estimated GFR and right atrial pressure (r = -0.195, p = 0.01), meaning higher right atrial pressures were correlated with decreased GFR.
Discussion: This paper clearly calls into question the assumption that renal dysfunction from acute heart failure is directly linked to renal hypoperfusion. Renal failure seen in acute heart failure is being increasingly called the "cardiorenal syndrome" in recognition of the more complex pathophysiology. Rather than renal arterial hypoperfusion, this trial along with other evidence suggests that elevated venous pressures may directly compromise renal function. One of the problems in extrapolating from trials like this is the complexity of interacting factors. The patients in this trial were sick and being treated with multiple agents like beta-blockers and ACE-I/ARB that also affect the renal vasculature. But, these pharmacologic confounders would be expected to affect vascular tone, and no correlation was found between systemic vascular resistance and renal dysfunction either. Besides the effects of elevated venous pressure, other possible explanations for renal dysfunction include undefined direct toxic effects of therapeutic agents. Also, many processes that worsen CHF, like HTN and diabetes, also have pathologic effects on the kidneys. In the coming years, we will likely learn more about the complex pathophysiology of cardiorenal syndrome!
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