Commentary by Srikant Duggirala MD, PGY-2
Please also see the clinical vignette presented during this week’s grand rounds
On Wednesday, October, 15, 2008, the NYU Department of Medicine Grand Rounds featured one of its own guest speakers, Stuart Katz M.D., Professor of Medicine and Director of Heart Failure at NYU School of Medicine, with his lecture entitled “Novel Applications of Erythropoietin in Cardiovascular Disease.”
Dr. Katz began his lecture with a discussion of oxygen uptake in a various individuals such as elite athletes and comparing their oxygen uptake ability to average individuals and also to heart failure patients. An elite athlete such as Lance Armstrong has an average maximum oxygen uptake 82ml/kg/min and this is compared to an average person who has an average maximum oxygen uptake of 36ml/kg/min and a heart failure patient who has an average maximum oxygen uptake of 12ml/kg/min. Utilizing the Fick equation (VO2 = COmax * (Arterial O2 sat. – Venous 02 sat.), it has been shown that patients with heart failure have increased ability to extract O2 more effectively than the average person. This is usually due to decreased capillary bed transit time and also due to increased erythropoietin levels.
Dr. Katz continued his discussion with the role of erythropoietin in heart failure and its potential use in patients with acute myocardial infarctions. Erythropoietin increases red cell mass and has been shown to increase the aerobic oxygen capacity in patients with heart failure. Additionally, molecular studies have shown that erythropoietin has a role in anti-apoptotic effects on cellular function and also induces expression of angiogenic signaling proteins. Studies have shown that erythropoietin receptors are upregulated in ischemic tissue, suggesting a protective role of erythropoietin during ischemic injury of myocardial tissue. While percutaneous coronary intervention has been shown to decrease the amount of tissue necrosis, erythropoietin has shown a decrease in the levels of apoptosis.
Some of the initial studies in rabbit hearts with the use of recombinant human erythropoietin (rHuEpo) have shown as much as a 60% decrease in infarct size and as much as 50% decrease in apoptotic signaling. In a 2006 study with canines, Epo was given at both 0 hours and at 6 hours. Again, Epo showed promising results with increased neovascularization.
The use of erythropoietin in clinical use has not been without significant controversy. It was a very aggressively marketed medication for treatment of anemia in chemotherapy patients for many years until studies suggested an increased risk of thrombosis in this patient population. The mechanism for increased risk of thrombosis is not entirely clear, but presumed to be at least one several mechanisms including increased red blood cell mass, increased platelet count, increased platelet aggregation and increased endothelial cell activation. Additionally, erythropoietin has been implicated with increased risk of hypertension and also promotion of tumor growth in cancer patients. It is important to highlight that these findings have been studied in cancer patients with long term use of erythropoietin. These findings have not been substantiated in the general population with short term use.
Dr. Katz continued his talk by discussing some of his research study findings with the erythropoietin in patients. His first study looked at the short term affects of erythropoietin and its affects in normal patients. The study utilized three different doses (100mg/kg x3day, 200mg/kg x3day, 400mg/kg x3 days) and a placebo group. All groups were also given high dose aspirin and plavix. The study concluded that high dose Epo was attributed to elevated platelet counts and also attenuated the effects of aspirin. It was presumed that the 200mg/kg dose was safer since these same side effects were not observed. Dr. Katz and his team followed up that study with another small study which showed on echocardiograms, patients had both a decreased left ventricular diastolic and systolic volume compared to placebo after ten days of receiving RhuEPO (Recombinant human erythropoietin). Dr. Katz concluded his discussion by describing a multi-center trial that is now beginning utilizing the erythropoietin in the acute management of STEMI. The initial studies look promising and this study will help define whether or not erythropoietin has a role in the management of acute myocardial infarctions.