Associations between vitamin D status, VDR gene polymorphisms and echocardiographic markers in Polish patients with cardiovascular disease.

Aim: This work was designed to investigate the associations between vitamin D metabolites, VDR gene polymorphisms and echocardiographic markers in a population of patients with cardiovascular disease. Methods: Echocardiographic markers for 42 patients were determined with tissue Doppler techniques. PCR-restriction fragment length polymorphism analysis identified genetic variants ApaI, TaqI, BsmI and FokI. A validated UHPLC-MS/MS method determined vitamin D metabolites. Results: Patients with the ApaI-GT genotype exhibited a lower pressure gradient across the aortic valve than ApaI-TT carriers. BMI, ApaI-GT, TaqI-TC, aortic arch diameter and maximal pressure gradient were significant univariate predictors of hypertension. Conclusion: A potential link exists between VDR gene polymorphisms and cardiovascular function.

Vitamin D levels in the body and variations in the vitamin D receptor gene are linked to specific heart-related markers in Polish patients with heart conditions. What is this article about? Coronary artery disease is a global health issue and the third leading cause of death. While many factors are understood to contribute to coronary artery disease, there is ongoing debate about whether vitamin D deficiency is one of them. In the past 10 years, there has been extensive research on vitamin D deficiency, characterizing it as a kind of 'pandemic' affecting a large portion of the population. Vitamin D deficiency is associated with more severe cardiovascular health issues and a higher risk of mortality. Why did we conduct this study? This study was designed to assess how different forms of vitamin D (created in the body) and genetic differences relate to heart health in people with cardiovascular disease and how they might be linked to markers observed in heart imaging. What were the results & what do they mean? Some genes seem to be more protective against hypertension than others. Some forms of vitamin D and genetic differences were linked to changes in markers observed in heart imaging. Adult patients should consume around 1000 to 2000 IU of vitamin D per day to contribute to better overall heart health.

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.

Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels.

Lipoprotein(a) [Lp(a)] is made up of a low-density lipoprotein (LDL) particle and a specific apolipoprotein(a). The blood concentration of Lp(a) is approximately 90% genetically determined, and the main genetic factor determining Lp(a) levels is the size of the apo(a) isoform, which is determined by the number of KIV2 domain repeats. The size of the apo(a) isoform is inversely proportional to the blood concentration of Lp(a). Lp(a) is a strong and independent cardiovascular risk factor. Elevated Lp(a) levels ≥ 50 mg/dl (≥ 125 nmol/l) are estimated to occur in more than 1.5 billion people worldwide. However, determination of Lp(a) levels is performed far too rarely, including Poland, where, in fact, it is only since the 2021 guidelines of the Polish Lipid Association (PoLA) and five other scientific societies that Lp(a) measurements have begun to be performed. Determination of Lp(a) concentrations is not easy due to, among other things, the different sizes of the apo(a) isoforms; however, the currently available certified tests make it possible to distinguish between people with low and high cardiovascular risk with a high degree of precision. In 2022, the first guidelines for the management of patients with elevated lipoprotein(a) levels were published by the European Atherosclerosis Society (EAS) and the American Heart Association (AHA). The first Polish guidelines are the result of the work of experts from the two scientific societies and their aim is to provide clear, practical recommendations for the determination and management of elevated Lp(a) levels.

Predictors of Revascularization in Patients with Unstable Angina.

BACKGROUND: The factors that determine the necessity of coronary artery revascularization in patients with unstable angina (UA) have been supported by limited data. Therefore, this study aimed to identify the predictors of revascularization in patients with UA. METHODS: The study included the recorded data of 3668 patients with UA who underwent cardiac catheterization (age 66 ± 9.2, men 70%); 2615 of them (71%) underwent revascularization (percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG), or hybrid revascularization. The remaining 1053 patients (29%) had no significant coronary stenosis and were regarded as controls. Multivariable logistic regression analysis was performed to separate the predictors of revascularization. RESULTS: It was found that severe angina (OR 2.7, 95%CI 1.9-3.7), male gender (OR 1.4, 95%CI 1.1-1.7), and hyperlipidemia were the predictors of revascularization. It was also noted that intraventricular conduction disorders including left and right bundle branch blocks and a history of previous revascularization and myocardial infarction were associated with lower odds of revascularization. CONCLUSION: Overall, however, the predictive value of the studied factors proved to be poor and may still point to the multifactorial nature of significant coronary artery stenosis and the need for revascularization in patients with UA.

Artificial intelligence in detecting left atrial appendage thrombus by transthoracic echocardiography and clinical features: the Left Atrial Thrombus on Transoesophageal Echocardiography (LATTEE) registry.

AIMS: Transoesophageal echocardiography (TOE) is often performed before catheter ablation or cardioversion to rule out the presence of left atrial appendage thrombus (LAT) in patients on chronic oral anticoagulation (OAC), despite associated discomfort. A machine learning model [LAT-artificial intelligence (AI)] was developed to predict the presence of LAT based on clinical and transthoracic echocardiography (TTE) features. METHODS AND RESULTS: Data from a 13-site prospective registry of patients who underwent TOE before cardioversion or catheter ablation were used. LAT-AI was trained to predict LAT using data from 12 sites (n = 2827) and tested externally in patients on chronic OAC from two sites (n = 1284). Areas under the receiver operating characteristic curve (AUC) of LAT-AI were compared with that of left ventricular ejection fraction (LVEF) and CHA2DS2-VASc score. A decision threshold allowing for a 99% negative predictive value was defined in the development cohort. A protocol where TOE in patients on chronic OAC is performed depending on the LAT-AI score was validated in the external cohort. In the external testing cohort, LAT was found in 5.5% of patients. LAT-AI achieved an AUC of 0.85 [95% confidence interval (CI): 0.82-0.89], outperforming LVEF (0.81, 95% CI 0.76-0.86, P < .0001) and CHA2DS2-VASc score (0.69, 95% CI: 0.63-0.7, P < .0001) in the entire external cohort. Based on the proposed protocol, 40% of patients on chronic OAC from the external cohort would safely avoid TOE. CONCLUSION: LAT-AI allows accurate prediction of LAT. A LAT-AI-based protocol could be used to guide the decision to perform TOE despite chronic OAC.

Machine learning model for predicting late recurrence of atrial fibrillation after catheter ablation.

Late recurrence of atrial fibrillation (LRAF) in the first year following catheter ablation is a common and significant clinical problem. Our study aimed to create a machine-learning model for predicting arrhythmic recurrence within the first year since catheter ablation. The study comprised 201 consecutive patients (age: 61.8 ± 8.1; women 36%) with paroxysmal, persistent, and long-standing persistent atrial fibrillation (AF) who underwent cryoballoon (61%) and radiofrequency ablation (39%). Five different supervised machine-learning models (decision tree, logistic regression, random forest, XGBoost, support vector machines) were developed for predicting AF recurrence. Further, SHapley Additive exPlanations were derived to explain the predictions using 82 parameters based on clinical, laboratory, and procedural variables collected from each patient. The models were trained and validated using a stratified fivefold cross-validation, and a feature selection was performed with permutation importance. The XGBoost model with 12 variables showed the best performance on the testing cohort, with the highest AUC of 0.75 [95% confidence interval 0.7395, 0.7653]. The machine-learned model, based on the easily available 12 clinical and laboratory variables, predicted LRAF with good performance, which may provide a valuable tool in clinical practice for better patient selection and personalized AF strategy following the procedure.

Cognitive Impairment in Cardiovascular Patients after Myocardial Infarction: Prospective Clinical Study.

(1) Background: Assessment of cognitive function is not routine in cardiac patients, and knowledge on the subject remains limited. The aim of this study was to assess post-myocardial infarction (MI) cognitive functioning in order to determine the frequency of cognitive impairment (CI) and to identify factors that may influence it. (2) Methods: A prospective study included 468 patients hospitalized for MI. Participants were assessed twice: during the first hospitalization and 6 months later. The Mini-Mental State Examination was used to assess the occurrence of CI. (3) Results: Cognitive dysfunction based on the MMSE was found in 37% (N-174) of patients during the first hospitalization. After 6 months, the prevalence of deficits decreased significantly to 25% (N-91) (p < 0.001). Patients with CI significantly differed from those without peri-infarction deficits in the GFR, BNP, ejection fraction and SYNTAX score, while after 6 months, significant differences were observed in LDL and HCT levels. There was a high prevalence of non-cognitive mental disorders among post-MI patients. (4) Conclusions: There is a high prevalence of CI and other non-cognitive mental disorders, such as depression, sleep disorders and a tendency to aggression, among post-MI patients. The analysis of the collected material indicates a significant impact of worse cardiac function expressed as EF and BNP, greater severity of coronary atherosclerosis expressed by SYNTAX results, and red blood cell parameters and LDL levels on the occurrence of CI in the post-MI patient population.

Position of the Polish Cardiac Society on therapeutic targets for LDL cholesterol concentrations in secondary prevention of myocardial infarctions.

Cardiovascular diseases account for 43% of deaths in Poland. The COVID-19 pandemic increased the number of cardiovascular deaths by as much as 16.7%. Lipid metabolism disorders are observed in about 20 million Poles. Lipid disorders are usually asymptomatic, they cause a significant increase in the risk of cardiovascular diseases. Up to 20% of patients who experience an acute coronary syndrome (ACS) may experience a recurrence of a cardiovascular event within a year, and up to 40% of these patients may be re-hospitalized. Within 5 years after a myocardial infarction, 18% of patients suffer a second ACS and 13% have got a stroke. Lipid-lowering therapy is an extremely important element of comprehensive management, both in primary and secondary prevention, and its main goal is to prevent or extend the time to the onset of heart or vascular disease and reduce the risk of cardiovascular events. A patient with a history of ACS belongs to the group of a very high risk of a cardiovascular event due to atherosclerosis. In this group of patients, low-density lipoprotein cholesterol levels should be aimed below 55 mg/dl (1.4 mmol/l). Many scientific guidelines define the extreme risk group, which includes not only patients with two cardiovascular events within two years, but also patients with a history of ACS and additional clinical factors: peripheral vascular disease, multivessel disease (multilevel atherosclerosis), or multivessel coronary disease, or familial hypercholesterolemia, or diabetes with at least one additional risk factor: elevated Lp(a) >50 mg/dl or hsCRP >3 mg/l, or chronic kidney disease (eGFR <60 ml/min/1.73 m²). In this group of patients, the LDL-C level should be aimed at below 40 mg/dl (1.0 mmol/l). Achieving therapeutic goals in patients after ACS should occur as soon as possible. For this purpose, a high-dose potent statin should be added to the therapy at the time of diagnosis, and ezetimibe should be added if the goal is not achieved after 4-6 weeks. Combination therapy may be considered in selected patients from the beginning. After 4-6 weeks of combination therapy, if the goal is still not achieved, adding a proprotein convertase subtilisin/kexin type 9 protein inhibitor or inclisiran should be considered. In order to increase compliance with the recommendations, Polish Cardiac Society and Polish Lipid Society propose to attach in the patient's discharge letter a statement clearly specifying what drugs should be used and what LDL-C values should be achieved. It is necessary to cooperate between the patient and the doctor, to follow the recommendations and take medicines regularly, to achieve and maintain therapeutic goals.

Echocardiographic predictors of thrombus in left atrial appendage-The role of novel transthoracic parameters.

Introduction: The left atrium appendage thrombus (LAAT) formation is a complex process. A CHA2DS2-VASc scale is an established tool for determining the thromboembolic risk and initiation of anticoagulation treatment in patients with atrial fibrillation or flutter (AF/AFL). We aimed to identify whether any transthoracic echocardiography (TTE) parameters could have an additional impact on LAAT detection. Methods: That is a sub-study of multicenter, prospective, observational study LATTEE (NCT03591627), which enrolled 3,109 consecutive patients with AF/AFL referred for transesophageal echocardiography (TEE) before cardioversion or ablation. Results: LAAT was diagnosed in 8.0% of patients. The univariate logistic regression analysis [based on pre-specified in the receiver operating characteristic (ROC) analysis cut-off values with AUC ≥ 0.7] identified left ventricular ejection fraction (LVEF) ≤ 48% and novel TTE parameters i.e., the ratios of LVEF and left atrial diameter (LAD) ≤ 1.1 (AUC 0.75; OR 5.64; 95% CI 4.03-7.9; p < 0.001), LVEF to left atrial area (LAA) ≤ 1.7 (AUC 0.75; OR 5.64; 95% CI 4.02-7.9; p < 0.001), and LVEF to indexed left atrial volume (LAVI) ≤ 1.1 (AUC 0.75, OR 6.77; 95% CI 4.25-10.8; p < 0.001) as significant predictors of LAAT. In a multivariate logistic regression analysis, LVEF/LAVI and LVEF/LAA maintained statistical significance. Calculating the accuracy of the abovementioned ratios according to the CHA2DS2-VASc scale values revealed their highest predictive power for LAAT in a setting with low thromboembolic risk. Conclusion: Novel TTE indices could help identify patients with increased probability of the LAAT, with particular applicability for patients at low thromboembolic risk.

Risk factors for left atrial thrombus in younger patients (aged < 65 years) with atrial fibrillation or atrial flutter: Data from the multicenter left atrial thrombus on transesophageal echocardiography (LATTEE) registry.

Background: Our aim was to assess the characteristics and to identify predictors of left atrial thrombus (LAT) in patients under age 65 with atrial fibrillation (AF) or atrial flutter (AFl). Methods: We conducted a subanalysis of a multicenter, prospective, observational study [the LATTEE registry]. Consecutive AF/AFl patients referred for cardioversion or ablation were enrolled. Results: Of the 3,109 patients included in the study, 1,276 were under age 65 (41%). Compared to non-LAT patients, those with LAT (n = 76) had higher CHA2DS2-VASc score (p < 0.001), more frequently had non-paroxysmal AF/AFl (p < 0.001), heart failure (p < 0.001), history of diabetes mellitus (p = 0.001), transient ischemic attack (p = 0.04), coronary artery disease (p = 0.02), and chronic kidney disease (p < 0.001). The LAT patients were also more often smokers (p = 0.004) and were more frequently treated with vitamin K antagonists (VKAs) (p < 0.001). Transthoracic echocardiography revealed a higher left atrial area (p < 0.001), lower left ventricular ejection fraction (LVEF) (p < 0.001), and lower value of LA appendage emptying volume in LAT than in non-LAT patients (p < 0.001). LVEF (OR 2.95; 95% CI: 1.32-6.59, p = 0.008), non-paroxysmal AF/AFl (OR 7.1; 95% CI: 2.05-24.63, p = 0.002) and treatment with VKAs (OR 4.92; 95% CI: 2.48-9.75, p < 0.001) were identified as independent predictors of LAT in younger patients. Conclusions: Our study, which focused on younger patients with AF/AFl, indicated substantial clinical and echocardiographic differences between participants with and without LAT. In the AF/AFl patients younger than age 65, the independent predictors of LAT included non-paroxysmal AF/AFl, lower LVEF, and treatment with VKAs.

Increased Body Mass Index and Risk of Left Atrial Thrombus in Nonvalvular Atrial Fibrillation Patients-Data from the Left Atrial Thrombus on Transesophageal Echocardiography (LATTEE) Registry.

An increased body mass index (BMI) is associated with a higher incidence of atrial fibrillation (AF) and a higher risk of thromboembolic complications in AF patients. The aim of this study was to investigate the effect of BMI on the risk of left atrial thrombi (LATs) in patients with nonvalvular AF/atrial flutter (AFl) (NV AF/AFl). Patients diagnosed with NVAF/AFl (between November 2018 and May 2020) were selected from the multicenter, prospective, observational Left Atrial Thrombus on Transesophageal Echocardiography (LATTEE) registry that included AF/AFl patients referred for cardioversion or ablation followed by transesophageal echocardiography. A total of 2816 AF/AFl patients (63.6% males; mean age 65.8 years; mean BMI 29.8 kg/m2) were included in the study. Two hundred and twenty-two of them (7.9%) had LATs. Compared with normal-weight patients, those with BMIs ≥ 25 kg/m2 more frequently presented clinical factors potentially provoking LATs, such as non-paroxysmal AF/AFl (p = 0.04), hypertension (p < 0.001), and diabetes (p < 0.001); had higher CHA2DS2 scores (p < 0.001); and had larger LA dimensions (LA diameter and LA area) (p < 0.001 for both parameters). On the other hand, they showed some features negatively related to thromboembolic risk; for example, they were younger (p < 0.001) and were more often male (p = 0.002). In addition, patients with abnormal BMIs were more likely to be smokers (p = 0.006) and to be treated with oral anticoagulants (p = 0.005). Despite these differences in the prevalence of thromboembolic risk factors, the incidence of LATs was not increased in patients with abnormal body weight (overweight and obese compared to normal-weight patients) in this large real-life cohort of AF/AFl patients. This is probably due to the balanced composition regarding the prevalence of positive and negative thromboembolic risk factors.

Heart failure and the risk of left atrial thrombus formation in patients with atrial fibrillation or atrial flutter.

AIMS: The aim of the study was to evaluate the prevalence of left atrial thrombus (LAT) on transoesophageal echocardiography (TOE) in patients with atrial fibrillation or atrial flutter (AF/AFl) with reference to the presence of heart failure (HF) and its subtypes. METHODS AND RESULTS: The research is a sub-study of the multicentre, prospective, observational Left Atrial Thrombus on Transoesophageal Echocardiography (LATTEE) registry, which comprised 3109 consecutive patients with AF/AFl undergoing TOE prior to direct current cardioversion or catheter ablation. TOE parameters, including presence of LAT, were compared between patients with and without HF and across different subtypes of HF, including HF with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF). HF was diagnosed in 1336 patients (43%). HF patients had higher prevalence of LAT than non-HF patients (12.8% vs. 4.4%; P < 0.001). LAT presence increased with more advanced type of systolic dysfunction (HFpEF vs. HFmrEF vs. HFrEF: 7.4% vs. 10.5% vs. 20.3%; P < 0.001). Univariate analysis revealed that HFrEF (odds ratio [OR] 4.13; 95% confidence interval [95% CI]: 3.13-5.46), but not HFmrEF or HFpEF, was associated with the presence of LAT. Multivariable logistic regression indicated that lower left ventricular ejection fraction (OR per 1%: 0.94; 95% CI 0.93-0.95) was an independent predictor of LAT formation. Receiver operator characteristic analysis showed LVEF ≤48% adequately predicted increased risk of LAT presence (area under the curve [AUC] 0.74; P < 0.0001). CONCLUSION: The diagnosis of HFrEF, but neither HFmrEF nor HFpEF, confers a considerable risk of LAT presence despite widespread utilization of adequate anticoagulation.

Left Atrial Thrombus in Atrial Fibrillation/Flutter Patients in Relation to Anticoagulation Strategy: LATTEE Registry.

Background: Atrial fibrillation (AF) and flutter (AFl) increase the risk of thromboembolism. The aim of the study was to assess the prevalence of left atrial thrombus (LAT) in AF/AFl in relation to oral anticoagulation (OAC). Methods: LATTEE (NCT03591627) was a multicenter, prospective, observational study enrolling consecutive patients with AF/AFl referred for transesophageal echocardiography before cardioversion or ablation. Results: Of 3109 patients enrolled, 88% were on chronic, 1.5% on transient OAC and 10% without OAC. Of patients on chronic OAC, 39% received rivaroxaban, 30% dabigatran, 14% apixaban and 18% vitamin K antagonists (VKA). Patients on apixaban were oldest, had the worst renal function and were highest in both bleeding and thromboembolic risk, and more often received reduced doses. Prevalence of LAT was 8.0% (7.3% on chronic OAC vs. 15% without OAC; p < 0.01). In patients on VKA, prevalence of LAT was doubled compared to patients on non-VKA-OACs (NOACs) (13% vs. 6.0%; p < 0.01), even after propensity score weighting (13% vs. 7.5%; p < 0.01). Prevalence of LAT in patients on apixaban was higher (9.8%) than in those on rivaroxaban (5.7%) and dabigatran (4.7%; p < 0.01 for both comparisons), however, not after propensity score weighting. Conclusions: The prevalence of LAT in AF is non-negligible even on chronic OAC. The risk of LAT seems higher on VKA compared to NOAC, and similar between different NOACs.

Vitamin D Receptor Gene Polymorphism and Vitamin D Status in Population of Patients with Cardiovascular Disease-A Preliminary Study.

The association between vitamin D receptor (VDR) polymorphism and the risk of cardiovascular diseases (CVD) remains unclear. This study aimed to assess a relationship between the VDR genotypes, plasma concentrations of vitamin D metabolites, and the occurrence of cardiovascular and metabolic disorders. Fifty-eight patients treated for various cardiological afflictions were included. Identification of VDR polymorphisms: ApaI, TaqI, BsmI, and FokI were carried out using the PCR-RFLP method. Plasma concentrations of 25-hydroxyvitamin-D2, 25-hydroxyvitamin-D3, and 3-epi-25-hydroxyvitamin D3 were assessed by the UPLC-MS/MS method. Lower incidence of BsmI AA genotype in the studied patients was observed compared with healthy controls, but the difference was insignificant. Among patients with the TT genotype, frequency of hypertension was higher than among carriers of other ApaI genotypes (p < 0.01). In addition, carriers of the TT ApaI, TC TaqI, and GA BsmI genotypes had an increased risk of obesity, while the presence of the FokI TT genotype was associated with a higher incidence of heart failure and hypertension. In conclusion, the BsmI AA genotype can be protective against CVD, but this observation needs study on a larger group of patients. Particular VDR genotypes were associated with 25-hydroxyvitamin-D levels, and the mechanism of this association should be further investigated.

Beneficial effects of empagliflozin on hematocrit levels in a patient with severe anemia.

INTRODUCTION: Sodium-glucose cotransporter (SGLT2) inhibitors may additionally benefit patients with diabetes by improving their erythropoiesis followed by the elevation of hemoglobin and hematocrit levels. REASON FOR THE REPORT: In the case described, severe normocytic normochromic anemia was resolved when empagliflozin had been introduced to the therapy. A 78-year-old male patient was admitted to our hospital with a non-ST-segment elevation myocardial infarction. His past medical history included diabetes, right coronary artery angioplasty, myocardial infarction and paroxysmal atrial fibrillation which required anticoagulant treatment. When examined, severe normocytic normochromic anemia was also diagnosed. About two years prior to his admission, the patient began suffering from persistent anemia despite the modification of his anticoagulant therapy with warfarin, rivaroxaban and dabigatran. An extensive evaluation failed to provide an explanation for his anemia. OUTCOME: Eventually, only the introduction of empagliflozin successfully increased the values of hemoglobin and hematocrit. Therefore, it transpires that SGLT2 enhances erythropoietin (EPO) secretion which subsequently raises hematocrit levels in patients with severe anemia.