Cardiac disease in the dialysis patient: good, better, best clinical practice.

UNLABELLED: Proven strategies to reduce cardiovascular events and cardiac mortality in hemodialysis patients are given on the basis of pathophysiology. This is an overview of our clinical know-how acquired during the last 30 years. We try to answer the following questions: (1) how to reduce cardiovascular events and cardiac mortality in hemodialysis patients; (2) how to achieve regression of left ventricular hypertrophy, the most important predictor of sudden cardiac death; (3) how to manage iron status during full correction of renal anemia to prevent iron deficiency-induced reactive thrombocytosis, which is recognized to cause fatal stroke and cardiovascular thrombosis; (4) how to maintain responsiveness to erythropoiesis-stimulating agents during correction of renal anemia, thereby avoiding unnecessarily high doses and so reaching ultimate cost-effectiveness. CONCLUSION: Normalization of renal anemia is not responsible for increased risk of cardiovascular events/cardiac mortality. The inability to adequately address iron status in hemoglobin normalization studies and the underprescription of effective cardiac/antihypertensive medication might explain the adverse outcome. Effective cardiac/antihypertensive medication, intensive iron therapy during normalization of hemoglobin, optimized correction of metabolic acidosis and supplementation of vitamins which are involved in the energy metabolism should be considered to significantly improve the outcome of hemodialysis patients.

Effects of optimized heart failure therapy and anemia correction with epoetin beta on left ventricular mass in hemodialysis patients.

BACKGROUND: In chronic hemodialysis (HD) patients, the presence and degree of left ventricular hypertrophy (LVH) correlates with mortality. Previous studies have shown that interventions, such as anemia correction or treatment of hypertension and/or chronic heart failure (CHF), can result in moderate regression of LVH. The primary objective of our study was to investigate the effects of a multi-interventional treatment strategy on LVH in HD patients. METHODS AND RESULTS: In a series of 202 consecutive HD patients, we combined optimized CHF therapy, including beta-blockers (BB), ACE inhibitors and angiotensin receptor blockers (ARBs), to target doses with full anemia correction by epoetin beta (hemoglobin (Hb) target males 14.5 g/dl, females 13.5 g/dl). Serial echocardiograms were recorded every 3-6 months. Mean follow-up was 3.4 +/- 1.2 years. Mean Hb at baseline was 11.4 +/- 1.4 vs. 14.6 +/- 1.6 g/dl (p < 0.001) at study end. There was a significant reduction in left ventricular mass index (LVMI, 159 +/- 65 vs. 132 +/- 46 g/m2 (p < 0.001)), an improvement in left ventricular ejection fraction (LVEF, 60 +/- 15 vs. 66 +/- 12% (p < 0.01)) and in NYHA class (2.8 +/- 0.76 vs. 1.96 +/- 0.76 (p < 0.01)) from baseline to follow-up in the overall study population. In a subgroup of 70 patients, LVMI returned to normal (169 +/- 33 vs. 114 +/- 14 g/m2 (p < 0.001)) after 1.4 +/- 1 years. CONCLUSIONS: Our study shows that optimized CHF therapy, in combination with anemia correction to normal Hb targets, results in a significant reduction of LVH, an increase in LVEF and an improvement in NYHA class. Moreover, in contrast to previous studies, our data also demonstrate that complete regression and prevention of LVH in HD patients is possible.

[Plasma amino acid concentrations in aggressive dogs]. / Aminosäure-Plasmakonzentrationen bei aggressiven Hunden.

Following the hypothesis that metabolic screens may be useful tools in the diagnosis of canine aggression we have investigated the blood plasma amino acid levels of dogs which have been found aggressive (N = 10) against dogs or men in comparison to non-aggressive dogs (N = 10). In summary, the aggressive dogs showed elevated plasma concentrations of the neurophysiological active aromatic amino acids tryptophan (46/171 micromol/l, p < 0,001), tyrosine (38/67 micromol/l, p < 0.01) and histidine (74/91 micromol/l, p < 0.01) and lower lysine concentrations (175/151 micromol/l, p < 0.05), which seems to point to a stress situation of these dogs. The nitrogen metabolism is impaired in the urea-cycle in the conversion of ornithine (17/34 micromol/l, p < 0.01) to citrulline (64/47 micromol/l). Higher levels of branched chain amino acids, especially leucine (122/150 micromol/l, p < 0.01), mainly metabolized in muscles, and isoleucin (60/71 micromol/l, p < 0.05) show a high energy potential. The acidose-stimulator methionine (48/78 micromol/l, p < 0.01) proved elevated. The results show that the changed behavior in the aggressive dogs is also reflected in their free amino acid plasma concentrations, independent of the question whether these data are the cause or the result of the aggressivity.

Optimized heart failure therapy and complete anemia correction on left-ventricular hypertrophy in nondiabetic and diabetic patients undergoing hemodialysis.

BACKGROUND: According to new guidelines, diabetes mellitus per se can be considered as stage I chronic heart failure (CHF). Available evidence suggests that patients suffering from both diabetes mellitus and renal insufficiency have disproportionately high rates of left-ventricular hypertrophy (LVH). METHODS: Optimized heart failure therapy, including beta-blockers, ACE-inhibitors and AT II-type-1-receptor-blockers, was prescribed in combination with complete anemia correction using epoetin beta (target hemoglobin: 13.5 g/dl for women; 14.5 g/dl for men) to 230 patients (55% male) with ambulatory hemodialysis, including 60 patients (52% male) with diabetes. Echocardiographic follow-up examinations were performed over a mean period of 4.4 +/- 1.2 years. RESULTS: Mean hemoglobin levels at the study end significantly increased to target levels in the entire study population and in patients with diabetes (both p < 0.001). Compared with baseline, significant improvements were seen in hemodialysis patients - both without and with diabetes - in left-ventricular mass index (-28.8 g/m2 [p < 0.001] and 29.0 g/m2 [p < 0.005], respectively), left-ventricular ejection fraction (+7.0% [p < 0.001] and +8.3% [p < 0.01], respectively) and in NYHA class (-0.84 [p < 0.01] and -1.12 [p < 0.01], respectively). Similar to the results in the overall population, a highly significant reduction in LVH (p < 0.005) and significant improvements in LVEF (p < 0.01) and NYHA class (p < 0.01) were seen in the high-risk subgroup of diabetic patients. CONCLUSIONS: Patients undergoing hemodialysis, with or without concomitant diabetes, benefit considerably from optimized, multifactorial heart failure therapy combined with complete anemia correction.