[RECOMMENDATIONS FOR CHANGING CARDIOVASCULAR SCREENING OF ATHLETES WHO ARE REQUIRED FOR PRE-PARTICIPATION SCREENING UNDER THE SPORTS LAW - A POSITION PAPER ON BEHALF OF THE ISRAEL HEART SOCIETY].

INTRODUCTION: For many years routine screening of athletes in Israel includes frequently performed ECGs and exercise tests that overload the system with questionable benefits. The purpose of the current document is to reevaluate the need for pre-participation testing and establish new evidence-based guidelines. It should be noted that our proposal for a change of approach relates only to subjects whose health questionnaire is normal, who do not have a family history of sudden and unexpected death at an early age, or a family history of hereditary heart disease and whose physical examination from a cardiovascular point of view is normal.

Potential roles in cardiac physiology and pathology of the cation channel TRPV2 expressed in cardiac cells and cardiac macrophages: a mini-review.

TRPV2 is a well-conserved channel protein expressed in almost all tissues. Cardiomyocyte TRPV2 is expressed in the intercalated disks of the cardiac sarcomeres, where it is involved in maintaining the proper mechanoelectric coupling and structure. It is also abundantly expressed in the intracellular pools, mainly the endoplasmic reticulum. Under pathological conditions, TRPV2 is translocated to the sarcolemma, where it mediates an abnormal [Ca]2+ entry that may contribute to disease progression. In addition, an intracellularly diffused TRPV2 expression is present in resident cardiac macrophages. Upon infection or inflammation, TRPV2 is engaged in early phagosomes and is, therefore, potentially involved in protecting the cardiac tissue. Following acute myocardial infarction, a profound elevated expression of TRPV2 is observed on the cell membrane of the peri-infarct macrophages. The macrophage TRPV2 may harbor a detrimental effect in cardiac recovery by increasing unfavorable migration and phagocytosis processes in the injured heart. Most reports suggest that while cardiac TRPV2 activation may be beneficial under specific physiological conditions, both cardiac- and macrophage-related TRPV2 blocking can significantly ameliorate disease progression in various pathological states. To verify this possibility, the time frame of TRPV2 overexpression and its mediated signaling need to be fully characterized in both cardiomyocyte and cardiac macrophage populations.

Acute kidney injury after transcatheter aortic valve implantation and mortality risk-long-term follow-up.

BACKGROUND: Acute kidney injury (AKI) complicating transcatheter aortic valve implantation (TAVI) is relatively frequent and associated with significant morbidity. Previous studies have shown a higher 30-day and 1-year mortality risk in patients with periprocedural AKI. Our aim was to identify the prognostic impact of periprocedural AKI on long-term follow-up. METHODS: This is a single-center prospective study evaluating patients undergoing TAVI for severe aortic stenosis. AKI was defined according to the Valve Academic Research Consortium 2 definition, as an absolute increase in serum creatinine ≥0.3 mg/dL or an increase >50% within the first week following TAVI. Mortality data were compared between patients who developed AKI and those who did not. Logistic and Cox regressions were used for survival analysis. RESULTS: The final analysis included 1086 consecutive TAVI patients. AKI occurred in 201 patients (18.5%). During the follow-up period, 289 patients died. AKI was associated with an increased risk of 30-day mortality {4.5 versus 1.9% in the non-AKI group; hazard ratio [HR] 3.70 [95% confidence interval (CI) 1.35-10.13]}. Although 1-year mortality was higher in the AKI group in univariate analysis, it was not significant after a multivariate regression. AKI was a strong predictor of longer-term mortality [42.3 versus 22.7% for 7-year mortality; HR 1.71 (95% CI 1.30-2.25)]. In 189 of 201 patients we had data regarding recovery from AKI up to 30 days after discharge. In patients with recovery from AKI, the mortality rate was lower (38.2 versus 56.6% in the nonrecovery group; P = 0.022). CONCLUSIONS: Periprocedural AKI following TAVI is a strong risk factor for short-term as well as long-term mortality (up to 7 years). Therefore more effort is needed to reduce this complication.

Elevated Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Structural versus Functional Renal Damage among ST-Segment Elevation Myocardial Infarction Patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of renal tubular damage. We investigated the incidence and possible implications of elevated NGAL levels (suggesting renal damage) compared to both functional and damage markers (manifested as serum creatinine [sCr] elevation) and no NGAL/sCr change, among -ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). METHODS: We included 131 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn 24 h following PCI. We used the terms NGAL(-) or NGAL(+) with levels ≥100 ng/mL suggesting renal tubular damage and the terms. sCr(-) or sCr(+) to consensus diagnostic increases in sCr defining acute kidney injury. Patients were also assessed for in hospital-adverse outcomes. RESULTS: Of the study patients, 56 (42%) were NGAL(-)/sCr(-), 58 (44%) NGAL(+)/sCr(-), and 18 (14%) were both NGAL(+)/sCr(+). According to the 3 study groups, there was a stepwise increase in the proportion of left ventricular ejection fraction ≤45% (43 vs. 60. vs. 72%; p = 0.04), in-hospital adverse outcomes (9 vs. 14 vs. 56%; p < 0.001) and their combination. Specifically, more NGAL(+)/sCr(-) patients developed the composite endpoint when compared to NGAL(-)/sCr(-) patients (64 vs. 46%; OR 2.1, [95% CI 1.1-4.5], p = 0.05). A similar and consistent increase was observed in peak sCr, length of hospital stay, and C-reactive protein levels. CONCLUSIONS: Elevated NGAL levels suggesting renal tubular damage, increased inflammation, or both are common among STEMI patients and are associated with adverse outcomes even in the absence of diagnostic increase in sCr.

Re-Appraisal of Echocardiographic Assessment in Patients with Pulmonary Embolism: Prospective Blinded Long-Term Follow-Up.

BACKGROUND: Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease. OBJECTIVES: To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE. METHODS: We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within < 24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results. RESULTS: Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC < 0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT) < 81 msec (P = 0.04), stroke volume < 44 cc (P = 0.005), and RIMP > 0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function. CONCLUSIONS: Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

Association of pre-admission statin therapy and the inflammatory response in ST elevation myocardial infarction patients.

PURPOSE: To demonstrate the possible association of statin therapy with C reactive protein (CRP) serial measurements in ST elevation myocardial infarction (STEMI) patients. MATERIALS AND METHODS: STEMI patients between 2008 and 2016 with available CRP data from admission were divided into two groups according to pre-admission statin therapy. A second CRP measurement was noted following primary coronary intervention (within 24 h from admission). The difference between the two measurements was designated ΔCRP. RESULTS: The cohort consisted of 1134 patients with a median age of 61 (IQR52-70), 81% males. Patients on statins prior to admission (336/1134, 26%) were more likely to have CRP levels within normal range (≤5 mg/l) compared to patients without prior treatment, both at admission (75 vs. 24%, p = 0.004) and at 24 h (70 vs. 48%, p = 0.029). The prevalence of patients with pre-admission statin therapy decreased as ΔCRP increased (p = 0.004; n = 301). The likelihood of ΔCRP to be above 5 mg/l in patients with pre-admission statin therapy was reduced after age and gender adjustments (OR 0.54, 95% CI 0.32-0.92, p = 0.023) and in multivariate (OR 0.57, 95% CI 0.33-0.99, p = 0.048) analysis. CONCLUSIONS: Pre-admission statin therapy is associated with a less robust inflammatory response in STEMI patients, highlighting statin's pathophysiological importance.

Downregulated Expression of TRPV2 in Peripheral Blood Cells following Acute Myocardial Infarction Is Inversely Correlated with Serum Levels of CRP and Troponin I.

OBJECTIVES: We have recently shown that the transient receptor potential vanilloid 2 (TRPV2) channel is exclusively upregulated in rat/murine peri-infarct monocytes/macrophages following an acute myocardial infarction (AMI), and that this overexpression might be detrimental for cardiac recovery. We aimed to characterize the expression levels of TRPV2 in peripheral blood mononuclear cells (PBMCs) of AMI patients relative to individuals with normal coronaries, and to analyze potential associations with inflammatory and cardiac ischemic markers. METHODS: Patients who underwent coronary angiography due to AMI or chest pain were prospectively included. PBMCs were isolated from whole blood by Ficoll gradient centrifugation. TRPV2 expression was analyzed by real-time PCR. C-reactive protein (CRP) and troponin I (TpI) levels were determined at the central chemistry laboratory; interleukin 6 and insulin-like growth factor (IGF)-1 levels were tested by ELISA. RESULTS: Following AMI, the number of TRPV2-expressing PBMCs was reduced when compared to in patients with normal coronaries. An inverse correlation was documented between the numbers of circulating macrophages and TRPV2 expression. Additionally, TRPV2 expression was inversely correlated with CRP and TpI and directly correlated with serum IGF-1. CONCLUSIONS: We assume that peripheral TRPV2 downregulation occurs concomitantly with the accumulation of TRPV2-white blood cells in the peri-infarct zone. TRPV2 may thus represent a novel target for treatment in the acute phase after MI.

Shift Work and the Risk of Coronary Artery Disease: A Cardiac Computed Tomography Angiography Study.

AIMS: Shift work disrupts the normal circadian rhythm and is associated with risk factors for coronary artery disease (CAD) and a higher incidence of CAD morbidity and mortality. Cardiac computed tomography angiography (CCTA) is a robust noninvasive modality for assessing the presence, extent, and severity of CAD. We sought to investigate whether shift workers are prone to a higher burden of CAD compared to non-shift workers. METHODS: We conducted a historically prospective study in consecutive patients who underwent CCTA and answered a telephonic questionnaire. Due to significant differences in age and gender, we compared 89 well-matched pairs of shift workers and non-shift workers with the use of propensity scores. RESULTS: Our cohort consisted of 349 participants, of whom 94 (26.9%) were shift workers. The mean age was 50.7 years, and 62.5% were males. After pairing, we showed that shift workers had a higher prevalence of CAD than non-shift workers (74.2 vs. 53.9%, respectively, p = 0.01), and a lower prevalence of coronary calcium scores of zero (46.8 vs. 63.4%, respectively, p = 0.034). Stenosis >50% was more prevalent in shift workers than in non-shift workers (20.2 vs. 11.2%, respectively, p = 0.006), and the extent of CAD (defined as the presence of ≥1-vessel disease) tended to be higher in shift workers than in non-shift workers (25.8 vs. 13.5%, respectively, p = 0.06). CONCLUSIONS: In this CCTA study, we showed in a well-matched cohort of consecutive patients that shift workers had a higher prevalence and extent of CAD than non-shift workers.

Diagnostic and Clinical Significance of T Wave Inversion in Athletes.

BACKGROUND: Electrocardiography abnormalities are a common finding in athletes. To facilitate the differentiation of physiological adaptation versus pathological remodeling, a series of guidelines has emerged in the past decade that attempt to improve specificity while maintaining a high sensitivity. Recently, T wave inversion in the athletic population gained more attention, resulting in accelerated research leading to novel findings not yet integrated into clinical practice. We aim to simplify the knowledge to date and integrate it into one easy to use practical flowchart.

CRP velocity and short-term mortality in ST segment elevation myocardial infarction.

CONTEXT: There is a known association between C-reactive protein (CRP) levels and adverse outcomes in patients presenting with ST-elevation myocardial infarction (STEMI). The optimal time frame to measure CRP for risk stratification is not known. OBJECTIVE: The aim of the current study was to evaluate the relation between the change in CRP velocity (CRPv) and 30-d mortality among STEMI patients. MATERIAL AND METHODS: We included consecutive patients with a diagnosis of STEMI who presented to Tel-Aviv Medical Center between 2008 and 2014 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24 h after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements. RESULTS: The study population comprised of 492 patients, mean age was 62 ± 14, 80% were male. CRPv was significantly higher among patients who died within 30 d of admission (1.42 mg/l versus 0.18 mg/l, p < 0.001). In a multivariate regression model adjusted to multiple confounders, CRPv was independently associated with 30-d mortality (OR 1.39, 95% CI: 1.20-1.62, p < 0.001). CONCLUSION: CRPv might be an independent and rapidly measurable biomarker for short-term mortality in patients presenting with STEMI.

Sex-based differences in prevalence and clinical presentation among pericarditis and myopericarditis patients.

BACKGROUND: Sex differences in heart diseases, including acute coronary syndrome, congestive heart failure, and atrial fibrillation, have been studied extensively. However, data are lacking regarding sex differences in pericarditis and myopericarditis patients. OBJECTIVES: The purpose of the study was to evaluate whether there are sex differences in pericarditis and myopericarditis patients as well. METHODS: We performed a retrospective, single-center observational study that included 200 consecutive patients hospitalized with idiopathic pericarditis or myopericarditis from January 2012 to April 2014. Patients were evaluated for sex differences in prevalence, clinical presentation, laboratory variables, and outcome. We excluded patients with a known cause for pericarditis. RESULTS: Among 200 consecutive patients, 55 (27%) were female. Compared with men, women were significantly older (60±19 years vs 46±19 years, P<.001) and had a higher rate of chronic medical conditions. Myopericarditis was significantly more common among men (51% vs 25%, P=.001). Accordingly, men had significantly higher levels of peak troponin (6.8±17 ng/mL vs 0.9±2.6 ng/mL, P<.001), whereas women presented more frequently with pericardial effusion (68% vs 45%, P=.006). Interestingly, women had a significantly lower rate of hospitalization in the cardiology department (42% vs 63%, P=.015). Overall, there were no significant differences in ejection fraction, type of treatment, complications, or in-hospital mortality. CONCLUSIONS: Most patients admitted with acute idiopathic pericarditis are male. In addition, men have a higher prevalence of myocardial involvement. Significant sex differences exist in laboratory variables and in hospital management; however, the outcome is similar and favorable in both sexes.

Decline in effort capacity with age: Echocardiographic stress analysis in the elderly.

BACKGROUND: The present study was designed to assess the underlying mechanism of decline in effort capacity seen with aging. METHODS: We analyzed 250 healthy senior patients (≥65 years) with an ejection fraction ≥60% who underwent a stress echocardiogram test. The seniors (aged 65-94) were divided into 3 equal age groups (groups 1, 2, and 3), and their echo characteristics at rest and peak exercise (measured and calculated) were compared. RESULTS: Diastolic function at rest declined significantly (E lateral, E septal, E/E', A) with age, while other rest parameters were similar. There was a significant reduction in peak cardiac output (CO) associated with age (time × age group interaction; P < .05), which was attributed to the combination an attenuated stroke volume (SV) and heart rate (HR) response. The decline in effort capacity with age was the product of the combined effect of cardiac (reduced LVEDV and HR response) and noncardiac (reduction in arteriovenous difference; P = .02 for interaction) causes. CONCLUSION: The cardiovascular system undergoes several age-related changes. Decline in effort capacity is an ongoing process of aging and consists of several changes in the cardiac and noncardiac systems, comprising a decline in CO and its components, specifically the peak exercise LVEDV, peak heart rate, and the ability of the muscles to extract enough oxygen for the necessary effort.

Increased CD11b+ cells and Interleukin-1 (IL-1) alpha levels during cardiomyopathy induced by chronic adrenergic activation.

BACKGROUND: Systemic CD11b+ cells have been associated with several cardiac diseases, such as chronic heart failure. OBJECTIVES: To assess the levels of circulating CD11b+ cells and pro-inflammatory cytokines in cardiomyopathy induced by chronic adrenergic stimulation. METHODS: Male Lewis rats were injected with low doses of isoproterenol (isoprel) for 3 months. Cardiac parameters were tested by echocardiography. The percentage of CD11b+ cells was tested by flow cytometry. The levels of inflammatory cytokines in the sera were determined by an inflammation array, and the expression levels of cardiac interleukin-1 (IL-1) receptors were analyzed by real-time polymerase chain reactions. Cardiac fibrosis and inflammation were determined by histological analysis. RESULTS: Chronic isoprel administration resulted in increased heart rate, cardiac hypertrophy, elevated cardiac peri-vascular fibrosis, reduced fractional shortening, and increased heart weight per body weight ratio compared to control animals. This clinical presentation was associated with accumulation of CD11b+ cells in the spleen with no concomitant cardiac inflammation. Cardiac dysfunction was also associated with elevated sera levels of IL-1 alpha and over expression of cardiac IL-1 receptor type 2. CONCLUSIONS: CD11b+ systemic levels and IL-1 signaling are associated with cardiomyopathy induced by chronic adrenergic stimulation. Further studies are needed to define the role of systemic immunomodulation in this cardiomyopathy.

Aortic regurgitation following transcatheter aortic valve replacement: Impact of preprocedural left ventricular diastolic filling patterns on late clinical outcomes.

OBJECTIVES: To investigate the impact of preprocedural left ventricular (LV) diastolic function on outcomes of patients with postprocedural aortic regurgitation (ARpost ) following transcatheter aortic valve replacement (TAVR). BACKGROUND: The predictors and mechanisms of the increased mortality in patients with ARpost are inadequately defined. METHODS: Baseline clinical and echocardiographic variables from a prospective TAVR registry were analyzed. Preprocedural correlates of late outcomes (all-cause mortality and the composite of mortality, stroke, heart failure, and new-onset atrial fibrillation) were examined according to the presence and severity of ARpost . RESULTS: Of the 418 patients undergoing TAVR, ARpost was present in 212 (51%): mild 36%, moderate-severe 15%. Mean follow-up was 909 ± 489 days. All-cause mortality and composite endpoint rates were significantly increased in patients with moderate-severe ARpost compared with patients with either none or only mild ARpost (38, 22, 21%, P = 0.02; and, 56, 35, 40%, P = 0.01; respectively). Moderate-severe (though not mild) ARpost was independently associated with mortality and the composite endpoint (HR = 1.93 [95%CI 1.15-3.14], P = 0.01; HR = 1.85 [95%CI 1.22-2.77], P = 0.004], respectively). By multivariate analysis, preprocedural LV deceleration time (DT) < 160 ms was independently associated with the risk of all-cause mortality and the composite endpoint among patients with mild AR (HR = 1.74 [95%CI 1.14-2.60], P = 0.01; and, HR = 1.73 [95%CI 1.23-2.41], P = 0.002, respectively) and moderate-severe ARpost (HR = 1.81 [95%CI 1.28-2.51], P < 0.001; HR = 1.86 [95%CI 0.22-2.80], P = 0.004, respectively). CONCLUSIONS: Preprocedural impairment of LV filling, reflected by short DT, portends an adverse prognosis in TAVR patients who develop ARpost independently of other clinical and echocardiocardigraphic measures including AS severity and systolic LV function. © 2015 Wiley Periodicals, Inc.

Differential Effects of Colchicine on Cardiac Cell Viability in an in vitro Model Simulating Myocardial Infarction.

OBJECTIVES: We aimed to examine the effects of colchicine, currently in clinical trials for acute myocardial infarction (AMI), on the viability of cardiac cells using a cell line model of AMI. METHODS: HL-1, a murine cardiomyocyte cell line, and H9C2, a rat cardiomyoblast cell line, were incubated with TNFα or sera derived from rats that underwent AMI or sham operation followed by addition of colchicine. In another experiment, HL-1/H9C2 cells were exposed to anoxia with or without subsequent addition of colchicine. Cell morphology and viability were assessed by light microscopy, flow cytometry and Western blot analyses for apoptotic markers. RESULTS: Cellular viability was similar in both sera; however, exposing both cell lines to anoxia reduced their viability. Adding colchicine to anoxic H9C2, but not to anoxic HL-1, further increased their mortality, at least in part via enhanced apoptosis. Under any condition, colchicine induced detachment of H9C2 cells from their culture plates. This phenomenon did not apply to HL-1 cells. CONCLUSIONS: Colchicine enhanced cardiomyoblast mortality under in vitro conditions mimicking AMI and reduced their adherence capability. HL-1 was not affected by colchicine; nevertheless, no salvage effect was observed. We thus conclude that colchicine may not inhibit myocardial apoptosis following AMI.

HbA1c Levels and Long-Term Mortality in Patients Undergoing Coronary Angiography.

OBJECTIVES: Previous studies investigating the prognostic value of HbA1c in patients undergoing coronary angiography reported a mixed pattern of results. Therefore, we aimed to better define the prognostic power of HbA1c among coronary catheterized patients. METHODS: Patients undergoing coronary angiography (n = 3,749) were divided into four groups according to HbA1c levels (<5, 5-6, 6-7 and >7%). Cox regression models assessed long-term mortality after adjusting for multiple covariates. RESULTS: Baseline clinical profiles differed in HbA1c groups, with a higher prevalence of comorbidities in the groups with higher HbA1c levels. Median follow-up was 1,745 days (interquartile range 1,007-2,171). A J-shaped association curve was observed between HbA1c levels and all-cause mortality rates, with patients in the lowest and highest HbA1c groups suffering from significantly higher mortality rates compared to in-between groups (hazard ratio 1.9, 95% CI 1.32-2.74, p = 0.001, and hazard ratio 1.58, 95% CI 1.29-1.95, p < 0.001, for the lowest and highest HbA1c groups, respectively). This association persisted after adjustment for anemia, nutritional status, renal function, cardiovascular risk factors and inflammatory biomarkers. CONCLUSIONS: HbA1c levels <5 or >7% are predictors of all-cause mortality in patients undergoing coronary angiography.

Relation of Pulmonary Artery Pressure and Renal Impairment in ST Segment Elevation Myocardial Infarction Patients.

BACKGROUND: Recent reports have demonstrated the adverse effects of venous congestion on renal function in patients having heart failure. None of the above trials, however, included patients with acute ischemia. HYPOTHESIS: Echocardiographic correlates of increased right ventricular afterload would be associated with an increased risk of acute kidney injury (AKI) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). METHODS: We conducted a retrospective study of consecutive 930 STEMI patients who underwent primary PCI and had a full echocardiography study performed within 72 hours of hospital admission between June 2011 and December 2014. RESULTS: Echocardiography demonstrated that patients with AKI had significantly lower left ventricular (LV) ejection fraction, higher systolic pulmonary artery pressure (SPAP), and right atrial pressures (P < 0.001 for all). Following the performance of logistic multivariate analysis model, SPAP (HR 1.07, 95% CI 1.04-1.11; P < 0.001) and LV ejection fraction (HR 0.95, 95% CI 0.92-0.99; P = 0.03) emerged as independent predictors of AKI. On receiver operating characteristic (ROC) curve analysis, the optimal cutoff value of SPAP to predict AKI was measured as more than 32 mmHg, with 71% sensitivity and 62% specificity (AUC 0.739, 95% CI 0.671-0.806, P < 0.001). CONCLUSIONS: Among STEMI patients undergoing primary PCI, worse LV function and elevated SPAP were associated with increased risk of AKI.

Down-Regulation of Cardiac Erythropoietin Receptor and its Downstream Activated Signal Transducer Phospho-STAT-5 in a Rat Model of Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is often accompanied by impairment of cardiac function that may lead to major cardiac events. Erythropoietin (EPO), a kidney-produced protein, was shown to be beneficial to heart function. It was suggested that reduced EPO secretion in CKD may play a role in the initiation of heart damage. OBJECTIVES: To investigate molecular changes in the EPO/ erythropoietin receptor (EPO-R) axis in rat cardiomyocytes using a rat model for CKD. METHODS: We established a rat model for CKD by kidney resection. Cardiac tissue sections were stained with Masson's trichrome to assess interstitial fibrosis indicating cardiac damage. To evaluate changes in the EPO/EPO-R signaling cascade in the myocardium we measured cardiac EPO and EPO-R as well as the phosphorylation levels of STAT-5, a downstream element in this cascade. RESULTS: At 11 weeks after resection, animals presented severe renal failure reflected by reduced creatinine clearance, elevated blood urea nitrogen and presence of anemia. Histological analysis revealed enhanced fibrosis in cardiac sections of CKD animals compared to the sham controls. Parallel to these changes, we found that although cardiac EPO levels were similar in both groups, the expression of EPO-R and the activated form of its downstream protein STAT-5 were significantly lower in CKD animals. CONCLUSIONS: CKD results in molecular changes in the EPO/EPO-R axis. These changes may play a role in early cardiac damage observed in the cardiorenal syndrome.