Left ventricular strain modifications after maximal exercise in athletes: a speckle tracking study.

PURPOSE: The increase in systolic indexes from rest (R) to exercise is achieved by combination of enhanced heart rate (HR) and stroke volume (SV). Aim of this study was to evaluate left ventricular (LV) longitudinal, circumferential, and torsional components immediately after a maximal intensity exercise (ME) by speckle tracking echocardiography (STE). METHODS: Twenty-seven male water polo players performed an ME that consisted of 6 repeats of 100 m freestyle swim sets. An echocardiographic examination was performed before and after ME. STE was performed to obtain the analysis of LV myocardial deformation. RESULTS: There were no differences between R and ME regarding LV longitudinal strains (PVLS). Apical circumferential LV strain (AVCS) and LV longitudinal strain rate (SR) increased at ME with respect to R (R: -23.1 ± 4.9%; ME: -28.4 ± 7.6%, P < 0.05; R: -1.1 ± 0.1/sec, ME: -1.5 ± 0.2/sec, P < 0.01). LV twisting (LVT) and untwisting (UTW) increased at ME (R: 7.9 ± 2.4°, ME: 14.2 ± 3.2°, P < 0.001; R: -107.2 ± 47.4; ME: -158.5 ± 61.5 °/sec; P < 0.01). At ME, apical rotation (Arot) had higher values than R values (5.4 ± 3.0°; 10.0 ± 6.0°; P < 0.01) and time-to-peak (TTP) of apical segments are earlier than all TTP. SV was related to LVT (r = 0.56, P = 0.01), AVCS (r = -0.59, P = 0.005) and Arot (r = 0.46, P = 0.04). At multivariate analysis, AVCS was the independent predictor of SV (ß = -0.58; P < 0.05). CONCLUSIONS: Apical fibers and LVT give the main contribution to systolic components at ME. The storage of energy during LVT, released during early diastole, seems to be a fundamental mechanism to support diastolic filling during maximal exercise.

Left ventricular twisting modifications in patients with left ventricular concentric hypertrophy at increasing after-load conditions.

AIMS: Left ventricular hypertrophy (LVH) develops as a result of several clinical conditions, such as intensive training, hypertension, aortic valve stenosis. Aim of this study was to analyze the left ventricular twist (LVT) modifications in LVH patients with increasing after-load conditions. METHODS: A total of 131 patients were enrolled: 17 healthy sedentary people (Hg), without concentric LVH; 45 water polo players (ATg); 22 patients with hypertensive cardiopathy (HPg); 47 patients with different degrees of aortic stenosis (ASg); all patients had concentric LVH, ejection fraction (EF) >54%, and were age-matched. The left ventricular end-systolic wall stress (LV-ESWS) was used as index of after-load. RESULTS: Left ventricular twist value showed a progressive increase from ATg to ASg, according to increasing after-load. Longitudinal left ventricular function by tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) was reduced in HPg and ASg. There was a negative correlation between LVT and longitudinal systolic function at TDI and STE (r = -0.4; P < 0.001; -0.23; P < 0.05). E/A ratio was lower in HPg and ASg than ATg and Hg. LVT was linearly related to LV-ESWS (r = 0.36; P < 0.01), E/A ratio (r = -0.59; P < 0.001), E/E' ratio (r = 0.43; P < 0.001), age (r = 0.5; P < 0.001), relative wall thickness (RWT) (r = 0.38; P < 0.01), heart rate (HR) (r = 0.3; P < 0.05), maximum (G. max), and mean transvalvular gradient (G. mean) in ASg (r = 0.37; P < 0.01, r = 0.4; P < 0.01). RWT, E/A ratio, and HR were independent predictor of LVT (ß = 0.23; P = 0.007; -0.44; P = 0.001; 0.17; P = 0.049). Only in ASg, G. mean was independent predictor of LVT (ß = 0.44; P = 0.01). CONCLUSION: Left ventricular twist showed a linear trend at increasing after-load values to compensate the reduction in systolic longitudinal function in pathological LVH patients.

Detection of early left ventricular and atrial dysfunction in overweight patients with preserved ejection fraction: a speckle tracking analysis.

BACKGROUND: Little remains known about the role of overweight to promote progressive atrial and ventricular myocardial dysfunction. Aim of this study was to investigate the potential influence of overweight on left ventricular (LV) and atrial (LA) function, as assessed by speckle tracking strain analysis, in patients at low-to-moderate global cardiovascular risk. METHODS: Seventy patients presenting 1 or more cardiovascular risk factor, with preserved ejection fraction, were enrolled. Peak atrial longitudinal strain (PALS) and Peak ventricular longitudinal strain (PVLS) were calculated by averaging values observed in all LV or LA segments, in four- and two-chamber views (global PALS and global PVLS), using a commercially available semiautomated two-dimensional (2D) strain software. RESULTS: Global PALS was similar in the 2 groups, while global PVLS was significantly lower in the overweight group as compared to normal weight (-17.2 ± 3.3 vs. -18.7 ± 2.8, P < 0.05). Univariate analysis of correlation showed a significantly correlation between global PALS and PVLS (r = -0.43, P < 0.01), as well as with E/A ratio (r = 0.40, P < 0.01) and with LV mass index (r = -0.34, P < 0.05). In multivariate linear regression analysis, these parameters were confirmed as independent predictors of PALS. CONCLUSION: In subjects at low-to-moderate cardiovascular risk, overweight is a key determinant of the reduction of global LV longitudinal function as assessed by 2D strain.

Double-Outlet Left Ventricle: Case Series and Systematic Review of the Literature.

Double-outlet left ventricle (DOLV) is an abnormal ventriculo-arterial connection characterized by the origin of both great arteries from the morphological left ventricle. The aim of our paper is to describe the morphological and imaging features of DOLV and to assess the prevalence of the associated malformations and their surgical outcomes. METHODS From 2011 to 2022, we retrospectively reviewed the electronic case records of patients diagnosed with DOLV at the Bambino Gesu Children's Hospital. A systematic search was developed in MEDLINE, Web of Science, and EMBASE databases to identify reports assessing the morphology and outcomes of DOLV between 1975 and 2023. RESULTS: Over a median follow-up of 9.9 years (IQR 7.8-11.7 y), four cases of DOLV were identified at our institution. Two patients were diagnosed with (S,D,D) DOLV subaortic VSD and pulmonary stenosis (PS): one patient had (S,D,D) DOLV with doubly committed VSD and hypoplastic right ventricle, and another patient had (S,D,L) DOLV with subaortic VSD and PS (malposition type). Pulmonary stenosis was the most commonly associated lesion (75%). LITERATURE REVIEW: After systematic evaluation, a total of 12 reports fulfilled the eligibility criteria and were included in our analysis. PS or right ventricular outflow tract obstruction was the most commonly associated lesion (69%, 95% CI 62-76%). The most common locations of VSD were subaortic (pooled prevalence: 75%, 95% CI 68-81), subpulmonary (15%, 95% CI 10-21), and doubly committed (7%, 95% CI 4-12). The position of the great arteries showed that d-transposition of the aorta was present in 128 cases (59% 95% CI 42-74), and l-transposition was present in 77 cases (35%, 95% CI 29-43).

Case Report: Two Case Reports of Acute Myopericarditis After mRNA COVID-19 Vaccine.

Background: Cases of myocarditis and myopericarditis after mRNA COVID-19 vaccines have been reported, especially after the second dose and in young males. Their course is generally benign, with symptoms onset after 24-72 h from the dose. Case Summary: We report two cases of myopericarditis after the second dose of the mRNA-1273 COVID-19 vaccine in two young males. Both the patients were administered the mRNA-1273 COVID-19 vaccine from the same batch on the same day and experienced fever on the same day of the vaccine, and symptoms consisted of myopericarditis 3 days after the dose. Discussion: Myopericarditis is usually considered an uncommon adverse reaction after various vaccinations, reported also after the mRNA COVID-19 vaccine. Several explanations have been proposed, including an abnormal activation of the immune system leading to a pro-inflammatory cascade responsible for myocarditis development. Both patients experienced the same temporal onset as well as the same symptoms, it is also useful to underscore that both vaccines belonged to the same batch of vaccines. However, despite these cases, vaccination against COVID-19 far outweighs the risk linked to COVID-19 infection and remains the best option to overcome this disease.

Anemia in Cardio-Renal Syndrome: clinical impact and pathophysiologic mechanisms.

Anemia is a disease that is often associated with heart failure (HF) and renal insufficiency (RI). This unfavorable triad of conditions has been called Cardio-Renal-Anemia Syndrome (CRS). The association of HF, RI, and anemia is poorly reported in multicenter clinical trials, so the pathophysiologic mechanisms and treatment options need to be better defined. When CRS patients develop anemia, a "perfect storm" often occurs: HF and RI cause anemia which will worsen the first two conditions. Anemia appears to be the result of complex interactions between cardiac performance, bone marrow homeostasis, renal dysfunction, and various drug side effects. However, neurohormonal and inflammatory activities play a key role in the beginning and progression of the disease. As a consequence, endogenous erythropoietin activity dysfunction with inadequate production and tissue resistance occurs. Despite the advances of therapy in the neurohormonal activation blockade, mortality and hospitalization in HF still remain unacceptably high, suggesting that specific comorbidity treatments could have a significant positive prognostic impact. Anemia should be recognized as one of the novel targets in HF treatment.

Left ventricular twisting as determinant of diastolic function: a speckle tracking study in patients with cardiac hypertrophy.

PURPOSE: Left ventricular hypertrophy (LVH) can develop in response to training with morphological changes in the heart and to pathological increase in afterload such as in essential hypertension. Deformation analysis using two-dimensional (2D) strain echocardiography can detect early systolic function abnormalities in patients with LVH. The aim of this study was to characterize left ventricular twisting (LVT) modifications, in professional athletes, compared with control subjects and with patients with hypertensive cardiopathy. METHODS: Seventy-six patients were enrolled: 37 professional athletes with cardiac hypertrophy (group A), 22 patients with early hypertensive cardiopathy (group B) cross-matched for LV mass index, and 17 healthy controls (group C), with no evidence of cardiac hypertrophy. All patients had no concomitant cardiac disease. All patients were investigated at rest using transthoracic echocardiography. LVT was obtained with speckle tracking analysis, using dedicated software. RESULTS: LVT was reduced in group A compared to group B and C (group A: 8.0° ± 2.4°; group C: 10.3° ± 2.3°; group B: 16.0° ± 4.2°; P < 0.01). In overall population, LVT showed a significant correlation with transmitral flow pattern (r =-0.58, P < 0.01) and with age (r =-0.57, P < 0.01). LVT showed the best predictive value to diagnose diastolic dysfunction (AUC: 0.86, P < 0.0001). CONCLUSIONS: 2D strain can identify specific patterns of myocardial deformation in professional athletes, controls, and patients with early hypertensive cardiopathy. In our study LVT showed a parallel trend with modifications of diastolic function and could represent a promising tool to differentiate functional cardiac hypertrophy from hypertensive cardiac hypertrophy.

Laser Ablation Treatment of Recurrent Lymph Node Metastases from Papillary Thyroid Carcinoma.

(1) Background: The incidence of papillary thyroid cancers is increasing. Papillary neoplasm metastasizes to the central and lateral lymph nodes of the neck. The recurrence rate is less than 30%. The gold standard of treatment for lymph node recurrences is surgery, but surgery is burdened by a high rate of complications. Therefore, laser ablation of recurrent lymph nodes has been recognized as an alternative treatment with minimal invasiveness, a low complication rate and a curative effect. (2) Methods: We analyzed 10 patients who underwent a total thyroidectomy and metabolic radiotherapy and who developed a lymph node recurrence in the laterocervical compartment in the following 12-18 months. (3) Results: Patients developed lymph node recurrence at IV and Vb levels in 70% and 30% of cases, respectively. All patients were treated with a single laser ablative session. Hydrodissection was performed in all patients. The energy delivered was 1120 ± 159.3 Joules and 3-4 Watts in 362 ± 45.7 s. No complications were reported. All patients underwent a 6-month follow-up. A volumetric reduction of 40.12 ± 2.2%, 49.1 ± 2.13% and 59.8 ± 3.05%, respectively at 1-, 3- and 6-months of follow-up was reported. (4) Conclusions: At 6 months, a fine needle aspiration was performed, which was negative for malignant cells and negative for a dosage of Thyroglobulin in eluate. The laser ablation is an effective alternative to surgical treatment.

Prospective study of sexual dysfunction in men with rectal cancer: feasibility and results of nerve sparing surgery.

PURPOSE: Rectal cancer surgery is impaired by a high rate of postoperative sexual dysfunction cause of frequent nerve injuries. The aim of this study was to prospectively evaluate sexual function in a group of male patients after total mesorectal excision (TME) for rectal cancer, using an autonomic nerve sparing technique. METHODS: All patients underwent autonomic nerve preserving TME. Sexual function was assessed using the International Index of Erectile Function standardized questionnaire. All patients were studied preoperatively and at 3, 6, 12, 18, and 24 months after surgery. RESULTS: Fifty-one patients with adenocarcinoma of the rectum were enrolled; after excluding 16 patients not sexually active, nine with T4 stage disease and six with metastatic disease, 20 patients were prospectively evaluated. The preoperative erectile function (EF) domain score of the International Index of Erectile Function was 24.3 (±4.1). The score of the EF domain was 17.6 (±7.5), 19.l9 (±7.2), 20.3 (±7.4), 20.5 (±7.4), and 20.6 (±7.4) at 3, 6, 12, 18, and 24 months after surgery. In the group of patients in which there were no macroscopic damages to the nerves, only two out of 15 (13.3%) developed erectile dysfunction. All five patients in whom incomplete pelvic nerve preservation was necessary developed erectile dysfunction. CONCLUSION: Our data show that nerve sparing technique can reduce the incidence of sexual dysfunction. Unfortunately, the technique is not applicable in every patient. Indications and techniques of autonomic nerve preservation are not standardized. Controlled trials with long-term follow-up seem to be necessary.

The Ablation of Thyroid Nodule's Afferent Arteries Before Radiofrequency Ablation: Preliminary Data.

Induced radiofrequency thermal ablation is the cytoreductive treatment of symptomatic benign thyroid nodules, metastatic and recurrent thyroid tumors and papillary thyroid microcarcinomas. It is a safe and effective alternative to surgery and it allows to obtain satisfactory results in terms of volumetric reduction of the nodule with significant improvement in the quality of life. The trans-isthmic approach and the moving shot technique are the two basic techniques; however, an advanced technique, artery-first feeding radiofrequency ablation, has been developed and validated. We have prospectively included 29 consecutive patients who have undergone radiofrequency ablation (Group A) or artery- first vRFA (Group B). All included patients had a diagnosis of benign nodular goiter and they underwent a single session of radiofrequency ablation. All patients followed a follow-up program at 1 month, 3 months, and 6 months. Continuous variables (age, TSH value, basal volume of nodule, used Joule, time in second of the procedure, nodules' volume at 1-, 3-, and 6- months of follow-up and percentage of volume reduction at 1-, 3-, and 6- months of follow-up) were described as mean, standard deviation and range, while categorical variables (gender, nodule structure and nodule vascularization) were described as number of cases and percentage. Independent samples t-test were performed to compare the continuous variables. A Test of Proportions was applied to the categorical variables. The Fisher's exact test was used to analyze the gender. Statistical significance was considered in case of p-value <0.05. Solid structure and spongiform structure showed statistic differences with p-values of 0.022 and 0.023 respectively between two groups. The percentage of reduction at 1 month did not show a significant difference between two groups; instead, the percentage of volume reduction was decreased mostly in the Group B at 3 months and 6 months of follow-up with a p-value of 0.003 and 0.013, respectively. The Joules/energy used showed a statistically significant difference (p-value=0.05), more energy must be used in vascular radiofrequency ablation. These data allow us to hypothesize that vRFA may improve the effectiveness of the procedure, allowing for a reduction in volume more quickly. They were preliminary but promising results, clearly a larger series of cases and prolonged follow-up are needed to clarify and confirm our observations.

Five-Year Results of Radiofrequency and Laser Ablation of Benign Thyroid Nodules: A Multicenter Study from the Italian Minimally Invasive Treatments of the Thyroid Group.

Background: Radiofrequency ablation (RFA) and laser ablation (LA) are effective treatments for benign thyroid nodules. Due to their relatively recent introduction into clinical practice, there are limited long-term follow-up studies. This study aimed to evaluate technique efficacy, rate of regrowth, and retreatment over 5 years after RFA or LA and to identify predictive factors of outcome. Methods: In this multicenter retrospective study, the rates of technique efficacy, regrowth, and retreatment were evaluated in 406 patients treated with either RFA or LA, and followed for 5 years after initial treatment. Propensity score matching was used to compare treatments. Cumulative incidence studies with hazard models were used to describe regrowth and retreatment trends, and to identify prognostic factors. Logistic regression models and receiver operating characteristic analyses were used for risk factors and their cutoffs. Results: RFA and LA significantly reduced benign thyroid nodule volume, and this reduction was generally maintained for 5 years. Technique efficacy (defined as a reduction ≥50% after 1 year from the treatment) was achieved in 74% of patients (85% in the RFA and 63% in the LA group). Regrowth occurred in 28% of patients (20% in the RFA and 38% in the LA group). In the majority of cases, further treatment was not required as only 18% of patients were retreated (12% in the RFA and 24% in the LA group). These data were confirmed by propensity score matching. Cumulative incidence studies showed that RFA was associated with a lower risk of regrowth and a lower risk of requiring retreatment over time. Overall, technique inefficacy and regrowth were associated with low-energy delivery. Retreatments were more frequent in young patients, in large nodules, in patients with lower volume reduction at 1 year, and in cases of low-energy delivery (optimal cutoff was 918 J/mL for RFA). Conclusions: Both thermal ablation techniques result in a clinically significant and long-lasting volume reduction of benign thyroid nodules. The risk of regrowth and needing retreatment was lower after RFA. The need for retreatment was associated with young age, large baseline volume, and treatment with low-energy delivery.

Left atrial strain after maximal exercise in competitive waterpolo players.

Left atrial (LA) function is a determinant of left ventricular (LV) filling. It carries out three main functions: reservoir, conduit, contractile. Aim of this study was to evaluate the role of LA and its deformation properties on LV filling at rest (R) and immediately after a maximal exercise (ME) through the speckle tracking echocardiography. Population enrolled was composed by 23 water polo athletes who performed a ME of six repeats of 100 m freestyle swim sets. At ME peak atrial longitudinal strain was reduced but all strain rate (SR) parameters increased, respectively positive peak SR at reservoir phase, SR negative peak at rapid ventricular filling (SRep) and SR negative peak at late ventricular filling (SRlp), that corresponds to atrial contraction phase. We showed a parallel increase in E and A pulsed Doppler wave and SRep and SRlp; particularly at ME, A wave and SRlp increased more respectively than E wave and SRep. SRlp was related to ejection fraction (EF) (r = -0.47; p < 0.01). At multivariate analysis SRlp was an independent predictor of EF (ß: -0.47; p = 0.016). The increased sympathetic tone results into increased late diastolic LV filling with augmented atrial contractility and a decrease in diastolic filling time. During exercise LV filling was probably optimized by an enhanced and rapid LA conduit phase and by a vigorous atrial contraction during late LV filling.

Age related diastolic function in amateur athletes.

Diastolic function get worse with increasing age. Aim of this study was to investigate the impact of aerobic training on diastolic function with increasing age with speckle tracking echocardiography. We enrolled 125 amateur swimmers (AG), divided in three groups at increasing age: young athletes, adult athletes (AG2), old athletes (AG3). We enrolled 95 sedentary controls (SG) age-matched with athletes and divided into three groups: young sedentary group, adult sedentary group (SG2) and old sedentary group (SG3). AG had better diastolic function than SG. AG showed lower left ventricular twist than controls. E/A ratio got worse at increasing of age in all population (r = -0.34; p < 0.001); particularly in SG2 and SG3 there was a worsening of diastolic function respect to diastolic function of AG2 and AG3; in fact E/A ratio decreased with aging. Furthermore in SG E/A ratio showed a linear correlation with age (r = -0.54; p < 0.001); in AG this correlation was lost. Therefore the training and age were independent predictor of E/A (respectively ß = -0.27; p = 0.004; ß = -0.24, p = 0.008). Regular and aerobic training may minimize aging changes of diastolic function. This training-effect may play a key role to preserve diastolic filling in older athletes.

Endurance and Strength Athlete's Heart: Analysis of Myocardial Deformation by Speckle Tracking Echocardiography.

BACKGROUND: Intensive training induces two morphological myocardial typologies of athlete's heart. Endurance training (ET) induces eccentric remodeling, bradycardia and better diastolic filling. Strength training (ST) determines concentric chamber remodelling maintaining a normal heart rate (HR). Aim of the study was to compare ET and ST athletes' heart using speckle tracking echocardiography (STE). METHODS: 33 professional ET, 36 ST athletes, and 17 healthy controls (CT) were enrolled. All subjects underwent standard transthoracic echocardiography at rest and STE. RESULTS: In ET group, HR was lower than ST group and CT group (p < 0.001; p < 0.01). ET group had higher E/A ratio than ST group and CT group (p < 0.01; p < 0.001). The left ventricular apical circumferential strain in ET group was lower than ST group and CT group (-21.6 ± 4.1% vs. -26.8 ± 7.7%, p < 0.05; vs. -27.8 ± 5.6%, p < 0.01). ET group had lower left ventricular twist (LVT) and untwisting (UTW) than ST group (6.2 ± 0.1° vs. 12.0 ± 0.1°, p < 0.01; -67.3 ± 22.9°/s vs. -122.5 ± 52.8°/s, p < 0.01) and CT group (10.0 ± 0.1°, p < 0.01; -103.3 ± 29.3°/s, p < 0.01). The univariate analysis showed significant correlation between E/A ratio and HR (r = -0.54; p < 0.001), LVT (r = -0.45; p < 0.01), UTW (r = 0.24; p < 0.05). At the multivariate analysis only HR was confirmed as independent predictor of diastolic function in all groups (Beta -0.52; p < 0.001). CONCLUSION: In ET there was a better global systolic and diastolic functional reserve at rest observed with strain analysis and it maybe depended on autonomic modulation.

Natriuretic peptides in heart failure: where we are, where we are going.

Tremendous advances have been made in understanding the pathophysiology and treatment of congestive heart failure (CHF). However, diagnosis still remains difficult, even with a comprehensive physical examination. Symptoms such as dyspnea are non-specific and poorly sensitive indicators for early CHF that can be largely undetected. The discovery of natriuretic peptides (BNP) as diagnostic biomarkers has been one of the most critical advances for heart failure diagnosis. Therefore, both B-type and N-terminal pro-B-type have potential role in the diagnosis of heart failure, as well as in prognostic risk assessment. A single determination of BNP at any time during the progression of chronic HF provides a clinically useful tool for risk stratification. The hypothesis that repeated measurements might carry prognostic information beyond a single measure was confirmed in different settings. One of the main interests is given to the values of repeated determinations for monitoring progression of disease, and for the evaluation of the clinical effects of medical therapy. Nevertheless, despite thousands of papers describing their potential utility, current guidelines have not endorsed the highest level of recommendation for their use, in part, because the application in clinical practice is often limited for the absence of well codified cut off. Recently, European guidelines emphasized the role of natriuretic peptides as potential laboratory markers. In the near future, algorithm building will take into consideration clinical and echocardiographic parameters as well as NP measurements, and this may lead to a correct diagnosis and identification of patients at high risk. The purpose of this review is to discuss the clinical approaches and future applications of natriuretic peptides in heart failure and coronary disease.

Anemia correction by erythropoietin reduces BNP levels, hospitalization rate, and NYHA class in patients with cardio-renal anemia syndrome.

Little is known about the effect of anemia correction with erythropoietin (EPO) on B-type natriuretic peptide (BNP) levels, NYHA class, and hospitalization rate. The aim of the study was to investigate, in patients with cardio-renal anemia syndrome, the effects of EPO on hemochrome and renal function parameters and BNP levels. We also analyzed the effect of EPO therapy on hospitalization rate and NYHA class after 12 months in comparison with a population undergoing to standard therapy. We performed a randomized double-blind controlled study of correction of the anemia with subcutaneous α (group A n = 13) or ß (group B n = 14) EPO for 12 months in addition to standard therapy with oral iron in 27 subjects. Control group (n = 25 patients) received only oral iron. Significant increase in hemoglobin (Hb), hematocrit (Hct), and red blood cells (RBC) were revealed in EPO groups at 12 months; Hb, group A 12.3 ± 0.6; group B 11.7 ± 0.8; control group 10.6 ± 0.5 g/dl P < 0.0001; Hct group A 34.2 ± 2.3, group B 34 ± 2, control group 32.3 ± 1.8% P < 0.01; RBC, group A 3.9 ± 0.2, group B 3.8 ± 0.2, control group 3.3 ± 0.2, (P < 0.0001). Plasma BNP levels in EPO groups were significantly reduced after 12 months (group A: 335 ± 138 vs. group B: 449 ± 274 pg/ml control group 582 ± 209 pg/ml (P < 0.01). After 12 months of treatment, hospitalization rate and NYHA class were reduced in EPO groups with respect to control group (P < 0.05). Finally, an inverse correlation was observed between BNP and Hb levels in EPO Groups (r = -0.70 P < 0.001). EPO treatment reduces BNP levels and hospitalization rate in patients with cardio-renal anemia syndrome. The correction of anemia by EPO treatment appears able to improve clinical outcome in this subset of patients with heart failure.