Soluble e-selectin is an inverse and independent predictor of left ventricular wall thickness in end-stage renal disease patients.

BACKGROUND: E-selectin is a specific endothelial cell product involved in leukocyte recruitment on the endothelium, which is an important early step in the reparative process following vascular damage. In end-stage renal disease (ESRD), the relationship of E-selectin with left ventricular function has been so far neglected. METHODS: We studied 237 patients on chronic dialysis (200 on hemodialysis, 37 on continuous ambulatory peritoneal dialysis) for at least 6 months, without clinical evidence of heart failure. On a mid-week non-dialysis day, fasting blood sampling and echocardiography were performed. RESULTS: Left ventricular mass index (LVMI, corrected for height) was inversely related to E-selectin levels, increasing from 56.8 +/- 18.9 (>75th percentile E-selectin tertile) to 66.7 +/- 20.1 g/m(2.7) (<50th percentile E-selectin tertile) (p = 0.002). However, in multiple regression models, including traditional (age, sex, smoking, diabetes, systolic blood pressure, hemoglobin, albumin, previous cardiovascular events) and emerging (asymmetric dimethylarginine, interleukin-6) risk factors associated with ESRD, soluble E-selectin has proved to be a significant inverse and independent predictor of mean wall thickness, but not of LVMI. CONCLUSION: This study demonstrates that soluble E-selectin is inversely associated with the muscular component of the left ventricle, thereby suggesting that the lack of such a reparative factor may be associated with cardiac remodeling in ESRD patients.

Early repolarization syndrome and Brugada syndrome: is there any linkage?

Early repolarization syndrome (ERS) is characterized by the presence, in most cases in mid-to-lateral precordial leads, of a J wave on the downsloping portion of the QRS complex, followed by an elevation of the ST-segment with upward concavity. ERS is considered a benign electrocardiographic pattern of ventricular repolarization and, thus far, clinical interest in this syndrome has been confined to its differential diagnosis from myocardial infarction and pericarditis. Brugada syndrome (BS), an inherited cardiac disease first described in 1992, exhibits a characteristic electrocardiographic pattern consisting of a J wave mimicking a right bundle branch block with typical ST-segment elevation in the right precordial leads. Believed to be a normal repolarization variant for more than three decades, the syndrome is now known instead to be associated with a high incidence of life-threatening ventricular tachyarrhythmias and is responsible for a number of sudden deaths in young adults worldwide. Although clinical findings seem to differentiate the two syndromes, similarities between BS and ERS in terms of response to heart rate, pharmacologic agents, and neuromodulation could suggest a linkage in their pathophysiological mechanism. The authors review the clinical and experimental data in order to test this hypothesis.

Brugada-like electrocardiographic pattern: a challenge for the clinician.

A right bundle branch block with ST-segment elevation in the V1-V3 leads in characteristic coved or saddleback configuration may be encountered as an incidental finding. However, not all patients with a Brugada-like electrocardiographic pattern are affected by the Brugada syndrome; in fact, this pattern may also be found in healthy individuals. Whether symptomatic patients affected by the syndrome are at a high risk of developing life-threatening ventricular arrhythmias and should immediately receive an automatic, implantable defibrillator is open to debate, as is the clinical management of asymptomatic patients, because data from the scientific literature are controversial. Implications of the diagnosis and the treatment of this category of patients are discussed.

Heart valve calcifications, survival, and cardiovascular risk in hemodialysis patients.

BACKGROUND: Cardiovascular (CV) calcifications constitute a strong risk marker, and recent studies in continuous ambulatory peritoneal dialysis patients have associated valvular calcifications to inflammation, mortality, and CV events. The prognostic value of cardiac valve calcifications and their relationship with left ventricular hypertrophy and background cardiovascular risk in hemodialysis patients is still unknown. METHODS: The prognostic value of heart valve calcifications (detected by echocardiography) for all-cause and CV death was tested in a cohort of 202 hemodialysis (HD) patients. RESULTS: Forty-seven patients had 1 or more calcified valves. Background CV complications were more frequent (P = 0.001) and left ventricular hypertrophy was more severe (P < 0.001) in patients with calcified valves than in those without this alteration. During the follow-up period (44 +/- 23 months), 96 patients died, 66 patients (69%) of CV causes. Valve calcifications were significantly associated with all-cause (P = 0.02) and CV mortality (P < or = 0.001). However, in statistical models adjusting for traditional and nontraditional CV risk factors and background CV complications and left ventricular mass index (LVMI), the relationship between calcified valves and incident all-cause and CV mortality was not significant. CONCLUSION: In HD patients, cardiac valve calcifications predict all-cause and CV mortality in unadjusted analyses, but these associations are not evident in models adjusting for background CV complications, LVMI, and other risk factors. Cardiac valve calcifications do not provide an independent contribution in the prediction of death and CV mortality.

Hepatocyte growth factor and left ventricular geometry in end-stage renal disease.

Hepatocyte growth factor is a pleiotropic cytokine with cardioprotective properties. Its serum concentration is markedly raised in end-stage renal disease. This study assessed the relation of hepatocyte growth factor (HGF) with left ventricular mass and geometry in end-stage renal disease. Serum HGF measurements and echocardiographic studies were performed in 185 patients receiving hemodialysis. Patients with serum HGF above the median (1.85 ng/mL) had more frequent cardiovascular complications. This cytokine was directly related to mean left ventricular wall thickness (r=0.23, P=0.002) and relative wall thickness (r=0.25, P=0.0001); a multivariate analysis showed that this relation was independent of other risk factors. Accordingly, the prevalence of left ventricular concentric geometry (either concentric left ventricular hypertrophy or remodeling) was much higher (n=49, 53%) among patients with HGF values above the median that in those with values < or =1.85 ng/mL (n=31, 34%). Furthermore, the risk for left ventricular concentric geometry was higher in patients with HGF values above the median (odds ratio, 2.57; 95% CI, 1.33 to 4.98; P=0.005), and multiple logistic regression analysis confirmed that this association was independent of other risk factors. In patients receiving hemodialysis, elevated serum HGF is associated with concentric left ventricular geometry. This is consistent with reports that link this cytokine to arterial remodeling and survival in patients with end-stage renal disease and suggests that it is part of a counterregulatory response aimed at attenuating cardiovascular damage in this high-risk population.

Diagnostic value of troponin T for alterations in left ventricular mass and function in dialysis patients.

BACKGROUND: Cardiac troponin T (cTnT) is related to left ventricular (LV) mass in patients with end-stage renal disease (ESRD). Furthermore, cTnT reflects the severity of systolic dysfunction in patients with heart diseases. We tested the diagnostic value of cTnT for left ventricular hypertrophy (LVH) and LV systolic dysfunction in a large group of clinically stable hemodialysis patients without heart failure. RESULTS: CTnT was significantly (P < 0.001) higher in patients with LVH than in those with normal LV mass. In a multiple logistic regression model, adjusting for potential confounders (including cardiac ischemia), systolic pressure and cTnT (both P = 0.003) were the strongest correlates of LVH. Similarly, cTnT was significantly higher (P = 0.005) in patients with systolic dysfunction than in those with normal LV function and in a multiple logistic regression model cTnT ranked as the second independent correlate of this alteration after male sex. Serum cTnT had a high positive prediction value for the diagnosis of LVH (87%) but its negative prediction value was relatively low (44%). The positive predictive value of cTnT for LV dysfunction was low (25%) while its negative predictive value was high (93%). A combined analysis including systolic pressure (for the diagnosis of LVH) and sex (for the diagnosis of LV systolic dysfunction) augmented the diagnostic estimates to an important extent (95% positive prediction value for LVH and 98% negative prediction value for LV systolic dysfunction). CONCLUSIONS: CTnT has a fairly good diagnostic potential for the identification of LVH and for the exclusion of LV systolic dysfunction in patients with ESRD without heart failure. This marker may be useful for the screening of alterations in LV mass and function in clinically stable hemodialysis patients.

Left ventricular hypertrophy, cardiac remodeling and asymmetric dimethylarginine (ADMA) in hemodialysis patients.

BACKGROUND: The endogenous inhibitor of nitric oxide (NO), asymmetric dimethylarginine (ADMA), is a strong predictor of adverse cardiovascular outcomes in patients with end-stage renal disease (ESRD). METHODS: Since arterial and cardiac remodeling is associated with altered endothelial microcirculatory responses to forearm ischemia (a NO-dependent response), interference of ADMA with the NO system may be important for the pathogenesis of left ventricular hypertrophy (LVH) in these patients. This study sought to identify the relationship between plasma ADMA and LV geometry and function in a cohort of 198 hemodialysis patients. RESULTS: Plasma ADMA was significantly higher (P = 0.008) in patients with LVH (median 3.00 micromol/L, inter-quartile range 1.73 to 3.97 micromol/L) than in those without this alteration (1.88 micromol/L, 1.15 to 3.56 micromol/L) and was significantly related to left ventricular (LV) mass (r = 0.26, P < 0.001). Interestingly, ADMA was much higher (P < 0.001) in patients with concentric LVH (3.60 micromol/L, 2.90 to 4.33 micromol/L) than in patients with eccentric LVH (2.17 micromol/L, 1.47 to 3.24 micromol/L) or normal LV mass (1.76 micromol/L, 1.13 to 2.65 micromol/L). Furthermore, plasma ADMA was higher (P = 0.02) in patients with systolic dysfunction (3.52 micromol/L, 2.08 to 5.87 micromol/L) than in those with normal LV function (2.58 micromol/L, 1.53 to 3.84 micromol/L) and inversely related to ejection fraction (EF; r = -0.25, P < 0.001). The link between ADMA and LV mass and EF was confirmed by multivariate analysis (ADMA vs. LVMI, beta = 0.17, P = 0.006; ADMA vs. EF, beta = -0.24, P < 0.001). CONCLUSIONS: Overall, this study indicates that raised plasma concentration of ADMA is associated to concentric LVH and LV dysfunction. Intervention studies are needed to see whether the link between ADMA and concentric LVH remodeling and LV dysfunction is a causal one.

Troponin is related to left ventricular mass and predicts all-cause and cardiovascular mortality in hemodialysis patients.

Cardiac troponin T (cTnT) predicts death and cardiovascular outcomes in clinically stable patients with end-stage renal disease. Because this protein is synthesized exclusively in myocardial cells, its predictive power for these outcomes may be because it reflects, besides cardiac ischemia, left ventricular (LV) mass, which is a strong predictor of cardiovascular death in this population per se. We tested the relationship between cTnT level and LV mass and the predictive power of this cardiac protein for all-cause and cardiovascular mortality in a cohort of hemodialysis patients (n = 199) without acute coronary syndrome and heart failure followed up for an average of 35 months (range, 0.8 to 52 months). cTnT was measured by means of a third-generation electrochemiluminescence immunoassay. cTnT level was related directly to interventricular septum (r = 0.36; P < 0.001) and posterior wall thickness (r = 0.40; P < 0.001), as well as LV mass (r = 0.45; P < 0.001). On multivariate analysis, after age, LV mass was the strongest independent predictor of cTnT level (beta = 0.28; P < 0.001). Serum cTnT level was significantly related to all-cause and cardiovascular mortality on univariate analysis (P < 0.001). On multivariate Cox regression analysis, the adjusted risk for all-cause death was 2.39 times (95% confidence interval [CI], 1.13 to 5.06; P = 0.02) greater in patients in the third cTnT tertile than the first tertile, and a similar pattern emerged for cardiovascular mortality (hazard ratio, 2.35; 95% CI, 1.01 to 5.49; P = 0.048). In hemodialysis patients, plasma cTnT level is independently related to LV mass and predicts all-cause and cardiovascular mortality. These data support the hypothesis that this marker can be usefully applied for risk stratification in clinically stable dialysis patients.

Hyperhomocysteinemia predicts cardiovascular outcomes in hemodialysis patients.

BACKGROUND: We prospectively tested the prediction power of homocysteinemia for all-cause and cardiovascular outcomes in a cohort of 175 hemodialysis patients followed for 29 +/- 12 months. METHODS: Survival analysis was performed by the Cox's proportional hazard model and data were expressed as hazard ratio and 95% confidence interval (CI). RESULTS: During the follow-up period 51 patients died, 31 of them (61%) of cardiovascular causes and 16 patients developed non-fatal atherothrombotic complications. Plasma total homocysteine was an independent predictor of cardiovascular mortality (P=0.01). Combined analysis of fatal and non-fatal atherothrombotic events showed that homocysteine was a strong and independent predictor of these outcomes because the risk of these events was 8.2 times higher (95% CI 1.9 to 32.2) in patients in the third homocysteine tertile than in those in the first tertile (P=0.005). CONCLUSIONS: There is a clear association between hyperhomocysteinemia and incident cardiovascular mortality and atherothrombotic events in hemodialysis patients. Intervention studies are needed to determine whether the accumulation of this substance has a causal role in the pathogenesis of cardiovascular damage in patients undergoing hemodialysis.

Cardiac natriuretic peptides are related to left ventricular mass and function and predict mortality in dialysis patients.

This study was designed to investigate the relationship among brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and left ventricular mass (LVM), ejection fraction, and LV geometry in a large cohort of dialysis patients without heart failure (n = 246) and to test the prediction power of these peptides for total and cardiovascular mortality. In separate multivariate models of LVM, BNP and ANP were the strongest independent correlates of the LVM index. In these models, the predictive power of BNP was slightly stronger than that of ANP. Both natriuretic peptides also were the strongest independent predictors of ejection fraction, and again BNP was a slightly better predictor of ejection fraction than ANP. In separate multivariate Cox models, the relative risk of death was significantly higher in patients of the third tertile of the distribution of BNP and ANP than in those of the first tertile (BNP, 7.14 [95% confidence interval (CI), 2.83 to 18.01, P = 0.00001]; ANP, 4.22 [95% CI, 1.79 to 9.92, P = 0.001]), and a similar difference was found for cardiovascular death (BNP, 6.72 [95% CI, 2.44 to 18.54, P = 0.0002]; ANP, 3.80 [95% CI, 1.44 to 10.03, P = 0.007]). BNP but not ANP remained as an independent predictor of death in a Cox's model including LVM and ejection fraction. Cardiac natriuretic peptides are linked independently to LVM and function in dialysis patients and predict overall and cardiovascular mortality. The measurement of the plasma concentration of BNP and ANP may be useful for risk stratification in these patients.