Can transesophageal echocardiography be safely omitted in patients scheduled for elective ablation of atrial arrhythmias? Data based on the LATTEE registry.

BACKGROUND: According to the present guidelines, transesophageal echocardiography (TEE) before scheduled catheter ablation (CA) for atrial arrhythmias (atrial fibrillation [AF] or atrial flutter [AFL]) is not deemed obligatory for optimally anticoagulated patients. However, daily clinical practice significantly differs from the recommendations. AIMS: That study aimed to identify transthoracic echocardiographic parameters that could be useful in revealing patients without left atrial thrombus (LAT), thereby contributing to avoiding unnecessary TEE before scheduled CA. METHODS: This is a sub-analysis of a multicenter, prospective, observational study - LATTEE registry. A total of 1346 patients referred for TEE before scheduled CA of AF/AFL were included. RESULTS: LAT was present in 44 patients (3.3%) and absent in the remaining 1302, who were younger, more likely to have paroxysmal AF, and displayed sinus rhythm during TEE. Additionally, they exhibited a lower incidence heart failure, diabetes, systemic connective tissue disease, and chronic obstructive pulmonary disease. Furthermore, they had a lower CHA2DS2-VASc score and a higher prevalence of direct oral anticoagulants. Echocardiographic parameters, including left ventricular ejection fraction (LVEF) > 65%, left atrial diameter (LAD) < 40 mm, left atrial area (LAA) < 20 cm2, left atrial volume (LAV) < 113 ml, and left atrial volume index (LAVI) < 51 ml/m2, demonstrated 100% sensitivity and 100% negative predictive value for the LAT absence, and weremet by 417 patients. Additional echocardiographic indices: LVEF/LAD > 1.4, LVEF/LAVI > 1.6 and LVEF/LAA > 2.7 identified an additional 57 patients, bringing the total predicted LAT-free patients to 474 (35%). CONCLUSIONS: Simple echocardiographic parameters could help identify individuals for whom TEE could be safely omitted before scheduled for elective CA due to atrial arrhythmias.

Differences in cardiac adaptation to exercise in male and female athletes assessed by noninvasive techniques: a state-of-the-art review.

Athlete's heart is generally regarded as a physiological adaptation to regular training, with specific morphological and functional alterations in the cardiovascular system. Development of the noninvasive imaging techniques over the past several years enabled better assessment of cardiac remodeling in athletes, which may eventually mimic certain pathological conditions with the potential for sudden cardiac death, or disease progression. The current literature provides a compelling overview of the available methods that target the interrelation of prolonged exercise with cardiac structure and function. However, this data stems from scientific studies that included mostly male athletes. Despite the growing participation of females in competitive sport meetings, little is known about the long-term cardiac effects of repetitive training in this population. There are several factors-biochemical, physiological and psychological, that determine sex-dependent cardiac response. Herein, the aim of this review was to compare cardiac adaptation to endurance exercise in male and female athletes with the use of electrocardiographic, echocardiographic, and biochemical examination, to determine the sex-specific phenotypes, and to improve the healthcare providers' awareness of cardiac remodeling in athletes. Finally, we discuss the possible exercise-induced alternations that should arouse suspicion of pathology and be further evaluated.

Feasibility and Safety of the Routine Distal Transradial Approach in the Anatomical Snuffbox for Coronary Procedures: The ANTARES Randomized Trial.

The distal transradial approach (dTRA) through the anatomical snuffbox is hypothesized to offer greater benefits than the conventional transradial access (cTRA) for patients undergoing coronary procedures. Our goal was to assess the safety and efficacy of dTRA. Out of 465 consecutive Caucasian patients, 400 were randomized (1:1) to dTRA or cTRA in a prospective single-center trial. Clinical and ultrasound follow-ups were obtained at 24 h and 60 days post-procedure. The primary combined endpoint consisted of access crossover, access-related complications, and major adverse cardiovascular events (MACE). Secondary endpoints included clinical success endpoints (puncture success, crossover, and access time), access-site complications endpoints, and MACE at 60 days. The primary endpoint was significantly higher in the dTRA [odds ratio (OR): 2.31, 95% confidence interval (CI): 1.38-3.86, p = 0.001]. Clinical success endpoints, namely crossover (10% vs. 3.5%, p < 0.05) and access-time [median: 140s (85-322) vs. 80s (58-127), p < 0.001], did not favor the dTRA, despite a similar success rate in radial artery puncture between the dTRA and cTRA (99.5% vs. 99%). Radial artery spasm (19% vs. 4.5%, p < 0.0001), physical discomfort during access, and transient thumb numbness after the procedure occurred more frequently with the dTRA. However, early (2.5% vs. 4.5%, p = 0.41) and mid-term (2.5% vs. 3%, p = 0.98) forearm radial artery occlusion rates were comparable between the dTRA and cTRA. Randomization to the dTRA, lower forearm radial pulse volume, higher body mass index, and lower body surface area independently predicted the primary endpoint in multivariate analysis. In the interaction effect analysis, only diabetes increased the incidence of the primary endpoint with the dTRA (OR: 18.67, 95% CI: 3.96-88.07). The dTRA was a less favorable strategy than cTRA during routine coronary procedures due to a higher incidence of arterial spasm and the necessity for access crossover. The majority of local complications following the dTRA were clinically minor complications. Individuals with diabetes were particularly susceptible to complications associated with the dTRA.

Diagnosis and treatment of transthyretin amyloidosis cardiomyopathy: A position statement of the Polish Cardiac Society.

Considering the rare incidence of transthyretin amyloidosis cardiomyopathy (ATTR-CM) in Poland, patients encounter difficulties at the stages of diagnosis and treatment. For successful diagnosis, it is vital to raise the suspicion of ATTR-CM, that is, to identify typical clinical scenarios such as heart failure with preserved ejection fraction or the red flags of amyloidosis. In most cases, it is possible to establish the diagnosis on the basis of noninvasive tests. This article presents the recommended diagnostic algorithms including laboratory workup, imaging tests (in particular, isotope scanning), and genetic tests. Since ATTR-CM should be differentiated from light chain amyloidosis, we also discuss aspects related to hematological manifestations and invasive diagnosis. We describe neurological signs and symptoms in patients with amyloidosis and present therapeutic options, including the causative treatment of ATTR-CM with the only currently approved drug, tafamidis. We also discuss drugs that are being assessed in ongoing clinical trials. We outline differences in the symptomatic treatment of heart failure in ATTR-CM and recommendations for nonpharmacological treatment and monitoring of the disease. Finally, we underline the need for providing access to the causative treatment with tafamidis as part of a drug program, as in other rare diseases, so that patients with ATTR-CM can be treated according to the European Society of Cardiology guidelines on heart failure and cardiomyopathy.

Case report: Transected Hickman catheter and its thrombotic occlusion in a patient with idiopathic pulmonary arterial hypertension-can a catheter replacement be avoided?

A 25-year-old female with idiopathic pulmonary arterial hypertension (PAH), who had a Hickman catheter implanted for continuous intravenous epoprostenol infusion, was admitted to the clinic after inadvertently cutting the catheter with nail scissors during a routine dressing change. Approximately 7 cm of the external segment of the Hickman catheter remained intact, with the distal end knotted by paramedics. A decision was made to repair the damaged Hickman catheter. However, it was discovered that its lumen was completely occluded by thrombosis. Therefore, catheter patency was mechanically restored using a 0.035-inch stiff guidewire in a sterile operating theatre setting, under fluoroscopy guidance. Successful aspiration and catheter flushing were achieved. Continuity of the Hickman catheter was then restored using a repair kit (Bard Access Systems) as per the manufacturer's instructions, with no visible leakage thereafter. Epoprostenol infusion through the Hickman catheter was resumed 24 h later, and the patient was discharged in good general condition two days afterward.

Echocardiographic Findings in Asymptomatic Mediastinal Lymphoma Survivors Years after Treatment Termination.

Patients treated due to mediastinal lymphomas are at risk of cardiovascular complications, as they receive chemotherapy, usually containing anthracyclines, often combined with thoracic radiotherapy. The aim of this prospective study was to assess early asymptomatic cardiac dysfunction using resting and dobutamine stress echocardiography (DSE) at least 3 years after the end of mediastinal lymphoma treatment. Two groups of patients were compared: those treated with chemoradiotherapy and those exclusively treated with chemotherapy. Left ventricular contractile reserve (LVCR) during DSE was assessed using changes in LV ejection fraction (LVEF), LV global longitudinal strain (LV GLS), and a novel parameter-Force, which is the ratio of the systolic blood pressure to the LV end-systolic volume. The study included 60 patients examined at a median of 89 months after the end of treatment. Resting echocardiography showed normal LVEF of 58.9 ± 9.6%, borderline LV GLS of -17.7 ± 3%, decreased mean stroke volume (SV) of 51.4 ± 17 mL, and indexed SV of 27.3 ± 8 mL/m2, and the right ventricular free wall longitudinal strain (LS) was impaired in some patients but not in all. There were no significant differences between the groups, with the exception of arterial hypertension, which was more common in the chemotherapy group (32% vs. 62.5%, p = 0.04). In resting echocardiography, only LV posterior wall LS differed significantly and was impaired in patients treated with chemotherapy (-19.1 ± 3.1% vs. -16.5 ± 5.1%, p = 0.04). DSE, performed in 21 patients after a median of 166 months from the end of cancer treatment, detected new contractility disorders in 1 patient (4.8%) and decreased LVCR in the majority of patients when determined using changes in LVEF or LV GLS, and in all patients when assessed with changes in Force. Conclusions: Most asymptomatic mediastinal lymphoma survivors showed preserved ventricular function on resting echocardiography. However, all of them showed impaired LV contractile reserve on DSE, as assessed with a simple parameter-Force. This may indicate subtle LV dysfunction and confirms the need for long-term monitoring of patients with potentially cardiotoxic cancer treatment.

Exercise-Induced Atrial Remodeling in Female Amateur Marathon Runners Assessed by Three-Dimensional and Speckle Tracking Echocardiography.

Endurance athletes have an increased risk of atrial remodeling and atrial arrhythmias. However, data regarding atrial adaptation to physical exercise in non-elite athletes are limited. Even less is known about atrial performance in women. We aimed to elucidate exercise-induced changes in atrial morphology and function in female amateur marathon runners using three-dimensional (3D) echocardiography and two-dimensional (2D) speckle tracking echocardiography (STE). The study group consisted of 27 female (40 ± 7 years) amateur athletes. Right (RA) and left atrial (LA) measures were assessed three times: 2-3 weeks before the marathon (stage 1), immediately after the run (stage 2), and 2 weeks after the competition (stage 3). Directly after the marathon, a remarkable RA dilatation, as assessed by RA maximal volume (RAVmax, 31.3 ± 6.8 vs. 35.0 ± 7.0 ml/m2; p = 0.008), with concomitant increase in RA contractile function [RA active emptying fraction (RA active EF), 27.7 ± 8.6 vs. 35.0 ± 12.1%; p = 0.014; RA peak atrial contraction strain (RA PACS) 13.8 ± 1.8 vs. 15.6 ± 2.5%; p = 0.016] was noticed. There were no significant changes in LA volumes between stages, while LA active EF (34.3 ± 6.4 vs. 39.4 ± 8.6%; p = 0.020), along with LA PACS (12.8 ± 2.1 vs. 14.9 ± 2.7%; p = 0.002), increased post race. After the race, an increase in right ventricular (RV) dimensions (RV end-diastolic volume index, 48.8 ± 11.0 vs. 60.0 ± 11.1 ml/m2; p = 0.001) and a decrease in RV function (RV ejection fraction, 54.9 ± 6.3 vs. 49.1 ± 6.3%; p = 0.006) were observed. The magnitude of post-race RV dilatation was correlated with peak RA longitudinal strain deterioration (r = -0.56, p = 0.032). The measured parameters did not differ between stages 1 and 3. In female amateur athletes, apart from RV enlargement and dysfunction, marathon running promotes transient biatrial remodeling, with more pronounced changes in the RA. Post-race RA dilatation and increment of the active contraction force of both atria are observed. However, RA reservoir function diminishes in those with post-race RV dilation.

Right Ventricular Endocardial Mapping and a Potential Arrhythmogenic Substrate in Cardiac Amyloidosis-Role of ICD.

Patients with cardiac amyloidosis (CA) have an increased risk of sudden cardiac death. (SCD). However, the role of an implantable cardioverter-defibrillator in the primary prevention of SCD in this group of patients is still controversial. We present a case with CA with recurrent syncope and non-sustained ventricular tachycardia. In order to further stratify the risk of SCD, an electrophysiological study with endocardial electroanatomic voltage mapping was performed prior to the ICD placement.

Hemodynamic Effects of Permanent His Bundle Pacing Compared to Right Ventricular Pacing Assessed by Two-Dimensional Speckle-Tracking Echocardiography.

We compared the effects of right ventricular (RVP; n = 26) and His bundle (HBP; n = 24) pacing in patients with atrioventricular conduction disorders and preserved LVEF. Postoperatively (1D), and after six months (6M), the patients underwent global longitudinal strain (GLS) and peak systolic dispersion (PSD) evaluation with 2D speckle-tracking echocardiography, assessment of left atrial volume index (LAVI) and QRS duration (QRSd), and sensing/pacing parameter testing. The RVP threshold was lower than the HBP threshold at 1D (0.65 ± 0.13 vs. 1.05 ± 0.20 V, p < 0.001), and then it remained stable, while the HBP threshold increased at 6M (1.05 ± 0.20 vs. 1.31 ± 0.30 V, p < 0.001). The RVP R-wave was higher than the HBP R-wave at 1D (11.52 ± 2.99 vs. 4.82 ± 1.41 mV, p < 0.001). The RVP R-wave also remained stable, while the HBP R-wave decreased at 6M (4.82 ± 1.41 vs. 4.50 ± 1.09 mV, p < 0.02). RVP QRSd was longer than HBP QRSd at 6M (145.0 ± 11.1 vs. 112.3 ± 9.3 ms, p < 0.001). The absolute value of RVP GLS decreased at 6M (16.32 ± 2.57 vs. 14.03 ± 3.78%, p < 0.001), and HBP GLS remained stable. Simultaneously, RVP PSD increased (72.53 ± 24.15 vs. 88.33 ± 30.51 ms, p < 0.001) and HBP PSD decreased (96.28 ± 33.99 vs. 84.95 ± 28.98 ms, p < 0.001) after 6 months. RVP LAVI increased (26.73 ± 5.7 vs. 28.40 ± 6.4 mL/m2, p < 0.05), while HBP LAVI decreased at 6M (30.03 ± 7.8 vs. 28.73 ± 8.7 mL/m2, p < 0.01). These results confirm that HBP does not disrupt ventricular synchrony and provides advantages over RVP.

Successful Catheter Ablation of the "R on T" Ventricular Fibrillation.

In patients with idiopathic ventricular fibrillation (VF), recurrent implantable cardioverter-defibrillator (ICD) shocks might increase mortality risk and reduce patients' quality of life. Catheter ablation of triggering ectopic beats is considered to be an effective method. We present a patient with recurrent VF, caused by the "R on T" premature ventricular complexes. In the presented case radiofrequency catheter ablation efficiently eliminated arrhythmia trigger, which was possible to detect thanks to the intracardiac electrocardiograms (ECG's) stored in the ICD.

Characteristics and outcomes of patients with chronic thromboembolic pulmonary hypertension in the era of modern therapeutic approaches: data from the Polish multicenter registry (BNP-PL).

BACKGROUND: Significant achievements in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) have provided effective therapeutic options for most patients. However, the true impact of the changed landscape of CTEPH therapies on patients' management and outcomes is poorly known. We aimed to characterize the incidence, clinical characteristics, and outcomes of CTEPH patients in the modern era of CTEPH therapies. METHODS: We analyzed the data of CTEPH adults enrolled in the prospective multicenter registry. RESULTS: We enrolled 516 patients aged 63.8 ± 15.4 years. The incidence rate of CTEPH was 3.96 per million adults per year. The group was burdened with several comorbidities. New oral anticoagulants (n = 301; 58.3%) were preferred over vitamin K antagonists (n = 159; 30.8%). Pulmonary endarterectomy (PEA) was performed in 120 (23.3%) patients and balloon pulmonary angioplasty (BPA) in 258 (50%) patients. PEA was pretreated with targeted pharmacotherapy in 19 (15.8%) patients, and BPA in 124 (48.1%) patients. Persistent CTEPH was present in 46% of PEA patients and in 65% of patients after completion of BPA. Persistent CTEPH after PEA was treated with targeted pharmacotherapy in 72% and with BPA in 27.7% of patients. At a mean time period of 14.3 ± 5.8 months, 26 patients had died. The use of PEA or BPA was associated with better survival than the use of solely medical treatment. CONCLUSIONS: The modern population of CTEPH patients comprises mostly elderly people significantly burdened with comorbid conditions. This calls for treatment decisions that are tailored individually for every patient. The combination of two or three methods is currently a frequent approach in the treatment of CTEPH. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov/ct2/show/NCT03959748.

Electrocardiographic Changes in Male and Female Amateur Marathon Runners: A Comparison Study.

Physical training is gaining popularity among amateurs. Males and females exhibit different cardiac adaptation to exercise. The aim of the study was to compare the incidence of electrocardiographic abnormalities before and after the marathon between sexes. 12-lead electrocardiogram was performed in 40 male (39±8 years) and 27 female (40±7 years) amateur runners: 2-3 weeks before (Stage 1) and immediately after (Stage 2) the marathon. Abnormalities in the resting (Stage 1) and exercise (Stage 2) electrocardiograms were compared between sexes. At rest left atrial enlargement was more frequent in females than males (48 vs. 20%; p<0.05). The incidence of right atrial enlargement was significantly more common at Stage 2 than 1, both in men (43 vs. 0%; p<0.001) and in women (48 vs. 4%; p=0.001). Significant increase of P-wave amplitude was found in male runners after the marathon (0.12±0.05 vs. 0.21±0.09 mV; p<0.001 Stage 1 vs. 2), but was absent in females. QTc prolongation was observed in both sexes, however to a higher degree in males (p<0.05 for the interaction stage and sex). Although both male and female amateur marathon runners exhibit abnormalities in resting and exercise electrocardiograms, men present more exercise-induced electrocardiographic changes, which might indicate a higher propensity for post-marathon arrhythmias. Electrocardiographic screening in amateurs should be considered.

The "athlete's heart" features in amateur male marathon runners.

BACKGROUND: Training on a professional level can lead to cardiac structural adaptations called the "athlete's heart". As marathon participation requires intense physical preparation, the question arises whether the features of "athlete's heart" can also develop in recreational runners. METHODS: The study included 34 males (mean age 40 ± 8 years) who underwent physical examination, a cardiopulmonary exercise test and echocardiographic examination (ECHO) before a marathon. ECHO results were compared with the sedentary control group, reference values for an adult male population and those for highly-trained athletes. Runners with abnormalities revealed by ECHO were referred for cardiac magnetic resonance imaging (CMR). RESULTS: The mean training distance was 56.5 ± 19.7 km/week, peak oxygen uptake was 53.7 ± 6.9 mL/kg/min and the marathon finishing time was 3.7 ± 0.4 h. Compared to sedentary controls, amateur athletes presented larger atria, increased left ventricular (LV) wall thickness, larger LV mass and basal right ventricular (RV) inflow diameter (p < 0.05). When compared with ranges for the general adult population, 56% of participants showed increased left atrial volume, indexed to body surface area (LAVI), 56% right atrial area and interventricular septum thickness, while 47% had enlarged RV proximal outflow tract diameter. In 50% of cases, LAVI exceeded values reported for highly-trained athletes. Due to ECHO abnormalities, CMR was performed in 6 participants, which revealed hypertrophic cardiomyopathy in 1 runner. CONCLUSIONS: "Athlete's heart" features occur in amateur marathon runners. In this group, ECHO reference values for highly-trained elite athletes should be considered, rather than those for the general population and even then LAVI can exceed the upper normal value.

Immune Checkpoint Inhibitors and Cardiac Toxicity in Patients Treated for Non-Small Lung Cancer: A Review.

Lung cancer is a major cause of cancer-related mortality worldwide, both in men and women. The vast majority of patients are diagnosed with non-small-cell lung cancer (NSCLC, 80-85% of lung cancer cases). Therapeutics named immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment in the last decade. They are monoclonal antibodies, and those directed against PD-1 (programmed cell death protein 1) or PD-L1 (programmed cell death-ligand 1) have been used in the treatment of lung cancer and significantly improved the prognosis of NSCLC patients. However, during treatment with ICIs, immune-related adverse events (irAEs) can occur in any organ and any tissue. At the same time, although cardiac irAEs are relatively rare compared to irAEs in other organs, they have a high mortality rate. The two most common clinical manifestations of immunotherapy-related cardiotoxicity are myocarditis and pericarditis. Various types of arrhythmias have been reported in patients treated with ICIs, including the occurrence of life-threatening complete atrioventricular block or ventricular tachyarrhythmias. Here, we aim to summarize the incidence, clinical manifestations, underlying mechanisms, diagnosis, and treatment strategies for ICI-associated cardiotoxicity as these issues become very important in view of the increasing use of ICI in the treatment of lung cancer.

Myocardial Injury and Overload among Amateur Marathoners as Indicated by Changes in Concentrations of Cardiovascular Biomarkers.

Marathons continue to grow in popularity among amateurs. However, the impact of intensive exercise on the amateur's cardiovascular system has not yet been studied. Analysis of the influence of the marathon on kinetics of biomarkers reflecting cardiac injury and overload may bring new insights into this issue. We investigated the effect of running a marathon on the concentrations of high sensitivity cardiac troponin I (hs-cTnI), heart-type fatty acid binding protein (H-FABP), N-terminal proatrial natriuretic peptide (NT-proANP), B-type natriuretic peptide (BNP), growth differentiation factor 15 (GDF-15) and galectin 3 (Gal-3) in the population of male amateur runners. The study included 35 amateur marathoners and followed 3 stages: S1-two weeks prior to the marathon, S2-at the finish line and S3-two weeks after. Blood samples were collected at each stage and analyzed for biomarkers and laboratory parameters. Concentrations of all studied biomarkers were significantly higher at S2, whereas at S3 did not differ significantly compared to S1. Running a marathon by an amateur causes an acute rise in biomarkers of cardiac injury and stress. Whether repetitive bouts of intensive exercise elicit long-term adverse cardiovascular effects in amateur marathoners needs further research.

Right Ventricular Diastolic Dysfunction after Marathon Run.

It has been raised that marathon running may significantly impair cardiac performance. However, the post-race diastolic function has not been extensively analyzed. We aimed to assess whether the marathon run causes impairment of the cardiac diastole, which ventricle is mostly affected and whether the septal (IVS) function is altered. The study included 34 male amateur runners, in whom echocardiography was performed two weeks before, at the finish line and two weeks after the marathon. Biventricular diastolic function was assessed not only with conventional Doppler indices but also using the heart rate-adjusted isovolumetric relaxation time (IVRTc). After the run, IVRTc elongated dramatically at the right ventricular (RV) free wall, to a lesser extent at the IVS and remained unchanged at the left ventricular lateral wall. The post-run IVRTc_IVS correlated with IVRTc_RV (r = 0.38, p < 0.05), and IVRTc_RV was longer in subjects with IVS hypertrophy (88 vs. 51 ms; p < 0.05). Participants with measurable IVRT_RV at baseline (38% of runners) had longer post-race IVRTc_IVS (102 vs. 83 ms; p < 0.05). Marathon running influenced predominantly the RV diastolic function, and subjects with measurable IVRT_RV at baseline or those with IVS hypertrophy can experience greater post-race diastolic fatigue.

Marathon Run-induced Changes in the Erythropoietin-Erythroferrone-Hepcidin Axis are Iron Dependent.

Alterations in iron metabolism after physical activity are manifested through the rise of blood hepcidin (Hpc) levels. However, in many athletes, no changes in Hpc levels are observed after exercise despite the presence of inflammation. The missing links could be erythropoietin (EPO) and erythroferrone (ERFE), which down-regulate Hpc biosynthesis. EPO, ERFE and Hpc biosynthesis is modified by serum iron through transferrin receptor 2. Consequently, we investigated whether marathon-induced changes in EPO, ERFE and Hpc levels are blood iron-dependent. Twenty-nine healthy male marathon runners were analyzed. Serum iron, ferritin, transferrin, EPO, ERFE and Hpc levels were assessed before, immediately after, and 9 ± 2 days after the marathon. The runners whose serum Hpc decreased after the marathon (n = 15), showed a significant increase in ERFE levels. In athletes whose serum iron levels were below 105 µg/day (n = 15), serum EPO (p = 0.00) and ERFE levels (p = 0.00) increased with no changes in Hpc concentration. However, in athletes with low serum iron, no changes in EPO levels were observed when serum ferritin exceeded 70 ng/mL (n = 7). Conversely, an increase in ERFE levels was observed in marathoners with low serum iron, independently of serum ferritin (n = 7). This indicates modulation of blood iron may affect exercise-induced changes in the EPO/ERFE/Hpc axis. Further study is needed to fully understand the physiological meaning of the interdependence between iron and the EPO/ERFE/Hpc axis.