Eligibility of sodium-glucose cotransporter-2 inhibitors in heart failure with preserved ejection fraction: Insights from the Colombian heart failure registry (RECOLFACA).

Background: The value of Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitor) therapy in individuals with heart failure with preserved EF (HFpEF) was unknown until the EMPEROR-Preserved trial. We aimed to assess the proportion of patients with HFpEF that are eligible for empagliflozin therapy within the Colombian Heart Failure Registry (RECOLFACA). Methods: RECOLFACA enrolled adult patients with a HF diagnosis during 2017-2019 from 60 medical centers in Colombia. Criteria of the EMPEROR-Preserved Trial were used to recruit participants. The main outcome was individual eligibility with N-terminal pro-B-type natriuretic peptide (NT-proBNP) criteria, while the secondary outcome was eligibility without NT-proBNP data. Results: RECOLFACA had 799 patients with HFpEF (mean age70.7 ± 13.5; 50.7 % males). According to the major selection criteria of the EMPEROR Preserved Trial, 73.7 % patients would be eligible for empagliflozin therapy initiation when considering the NT-proBNP threshold. The NT-proBNP threshold represented the main determinant of ineligibility in patients with this biomarker measure (13.6 %; n = 16). In patients without NT-proBNP data, the main reasons for exclusion were the diagnosis of symptomatic hypotension or a systolic blood pressure below 100 mmHg (7.5 %), having an eGFR < 20 ml/min/1.73 m2 (4.3 %), and haemoglobin < 9 g/dl (3.1 %). Excluding NT-proBNP criteria increased empagliflozin eligibility to 80.6 %. Conclusion: Most patients with HFpEF from RECOLFACA are potential candidates for empagliflozin therapy initiation according to the EMPEROR-Preserved trial criteria. These findings favor the utilization of SGLT-2 inhibitor medications in daily medical practice, which may further decrease morbidity and mortality in HF patients, regardless of their EF classification.

A Single-Cell Taxonomy Predicts Inflammatory Niche Remodeling to Drive Tissue Failure and Outcome in Human AML.

Cancer initiation is orchestrated by an interplay between tumor-initiating cells and their stromal/immune environment. Here, by adapted single-cell RNA sequencing, we decipher the predicted signaling between tissue-resident hematopoietic stem/progenitor cells (HSPC) and their neoplastic counterparts with their native niches in the human bone marrow. LEPR+ stromal cells are identified as central regulators of hematopoiesis through predicted interactions with all cells in the marrow. Inflammatory niche remodeling and the resulting deprivation of critical HSPC regulatory factors are predicted to repress high-output hematopoietic stem cell subsets in NPM1-mutated acute myeloid leukemia (AML), with relative resistance of clonal cells. Stromal gene signatures reflective of niche remodeling are associated with reduced relapse rates and favorable outcomes after chemotherapy across all genetic risk categories. Elucidation of the intercellular signaling defining human AML, thus, predicts that inflammatory remodeling of stem cell niches drives tissue repression and clonal selection but may pose a vulnerability for relapse-initiating cells in the context of chemotherapeutic treatment. SIGNIFICANCE: Tumor-promoting inflammation is considered an enabling characteristic of tumorigenesis, but mechanisms remain incompletely understood. By deciphering the predicted signaling between tissue-resident stem cells and their neoplastic counterparts with their environment, we identify inflammatory remodeling of stromal niches as a determinant of normal tissue repression and clinical outcomes in human AML. See related commentary by Lisi-Vega and Méndez-Ferrer, p. 349. This article is featured in Selected Articles from This Issue, p. 337.

Prevalence, Clinical Characteristics, and Prognostic Impact of Kidney Disease on Heart Failure Patients: An Observational Study of the Colombian Heart Failure Registry.

INTRODUCTION: Chronic kidney disease (CKD) represents one of the most frequent comorbidities observed in heart failure (HF) patients and has been observed to increase this population's risk of adverse outcomes. Nevertheless, evidence analyzing kidney dysfunction in HF is scarce in Latin American populations. We aimed to analyze the prevalence of kidney dysfunction and assess its association with mortality in patients diagnosed with HF enrolled in the Colombian Heart Failure Registry (RECOLFACA). METHODS: RECOLFACA enrolled adult patients with HF diagnosis from 60 centers in Colombia during the period 2017-2019. The primary outcome was all-cause mortality. A Cox proportional-hazards regression model was used to assess the impact of the different categories of eGFR in mortality risk. A p value of <0.05 was considered significant. All statistical tests were two-tailed. RESULTS: From the total 2,514 evaluated patients, 1,501 (59.7%) patients had moderate kidney dysfunction (eGFR <60 mL/min/1.73 m2), while 221 (8.8%) patients were classified as having a severe kidney dysfunction (eGFR <30 mL/min/1.73 m2). Patients with lower kidney function were most commonly males, had higher median age, and reported a higher prevalence of cardiovascular comorbidities. Moreover, different patterns of medications prescription were observed when comparing CKD versus non-CKD patients. Finally, eGFR <30 mL/min/1.73 m2 was significantly associated with a higher mortality risk compared to eGFR >90 mL/min/1.73 m2 status (HR: 1.87; 95% CI, 1.10-3.18), even after an extensive adjustment by relevant covariates. CONCLUSION: CKD represents a prevalent condition in the setting of HF. Patients with CKD and HF present with multiple sociodemographic, clinical, and laboratory differences compared with those only diagnosed with HF and present a significantly higher risk of mortality. A timely diagnosis and optimal treatment and follow-up of CKD in the setting of HF may improve the prognosis of these patients and prevent adverse outcomes.