Jacob Allan Udell

BACKGROUND: The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America heart failure (HF) classification incorporates cardiac biomarkers to identify early risk of HF. The HF stages may also guide the prognosis and management of cardiovascular and kidney-related events. METHODS: SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) was a randomized trial in diabetes with kidney disease comparing sotagliflozin versus placebo on cardiovascular death, HF hospitalizations, and urgent HF visits. SCORED participants were grouped by HF stage post hoc. Stage A: no HF, normal biomarkers (NT-proBNP [N-terminal pro-B-type natriuretic peptide] <125 pg/mL; high sensitivity cardiac troponin T [hs-cTnT] 2- and 5-fold, respectively. The benefits of sotagliflozin are consistent, irrespective of HF stage.

Background: Sodium glucose co-transport inhibitors (SGLT2i), although established heart failure (HF) therapy in acquired heart disease, are not well-studied in adult congenital heart disease (ACHD). We aimed to conduct a systematic review and meta-analysis of SGLT2i therapy in moderate or severe complexity ACHD. Methods: Five databases (Pubmed, Medline, Embase, SCOPUS, and Cochrane) were searched for peer-reviewed journal articles describing SGLT2i HF therapy in moderate or severe complexity ACHD. Outcomes included adverse clinical events, biochemical markers of HF (N-terminal pro-brain natriuretic peptide [NT-proBNP] or BNP), and imaging markers of cardiac function (global longitudinal strain [GLS] and fractional area change [FAC]). Forest plots demonstrated mean study effects as individual and pooled estimates. The impact of heterogeneity on the overall variance was evaluated. Results: The systematic review included 10 studies (n=174 patients, 60% male). SGLT2i therapy was associated with a statistically significant improvement in GLS (mean difference -1.6 [-2.4,-0.9]) but not FAC (mean difference +1.86 [-6.2,+9.9]); there was no significant post therapy change in NT-proBNP or BNP (mean difference -240 pg/mL [-516,45] and -52 pg/mL [-129,26], respectively). Heterogeneity for the pooled effects for GLS and FAC was low (I2=0%), although moderate to high for NT-proBNP and BNP (I2=47% and I2=90%, respectively). Data were insufficient for evaluation of SGLT2i impact on clinical outcomes. Conclusions: Pooled results across studies suggest that SGLT2i therapy can improve GLS among people with ACHD-HF, however the clinical implications of this observation warrant further study. Randomized controlled trials are now needed to evaluate the impact of SGLT2i therapy in ACHD.

Key Points: The effIcacy, mechaNisms and saFety of SGLT2 INhibitors in kIdney Transplant recIpients trial assessed the physiologic effects of sodium-glucose cotransporter-2 inhibitors in kidney transplant recipients. In kidney transplant recipients, sodium-glucose cotransporter-2 inhibitors lowered mean arterial pressure after 1 week, reduced GFR, increased glucosuria, and were safe. Dapagliflozin was well tolerated in kidney transplant recipients, showing similar cardio-kidney effects seen in other groups; outcome trials in kidney transplant recipients are now needed. Background: Cardiovascular and kidney protective mechanisms with 12 weeks of sodium-glucose cotransporter-2 inhibitor treatment (dapagliflozin 10 mg daily) were assessed in kidney transplant recipients (KTR) with and without type 2 diabetes. Methods: This randomized double-blind, parallel-group, placebo-controlled study enrolled 52 KTR and comprised three sequential physiologic assessments under clamped euglycemia (4–6 mmol/L): baseline, at 1, and 12 weeks of treatment. The primary objective was to evaluate BP lowering with dapagliflozin. Secondary outcomes were iohexol-measured GFR, natriuresis, body composition, noninvasive cardiac output monitoring, arterial stiffness, heart rate variability, neurohormones, and safety. Results: Fifty-one KTR completed the study—mean age 53±13 years, 62% with hypertension, 57% with type 2 diabetes, 50% on renin-angiotensin-aldosterone system inhibitors, and mean eGFR 68.2±24.4 ml/min per 1.73 m ² . Compared with placebo, dapagliflozin did not lower systolic BP at 1 or 12 weeks, although it did reduce mean arterial pressure after 1 week (3.9 mm Hg; 95% confidence interval [CI], −7.5 to −0.2). Dapagliflozin led to significant, placebo-adjusted reductions in iohexol-measured GFR from baseline to 1 week (4.2 ml/min per 1.73 m ² ; 95% CI, −7.14 to −1.24 ml/min per 1.73 m ² ) and 12 weeks (−3.49 ml/min per 1.73 m ² ; 95% CI, −6.33 to −0.64). Dapagliflozin significantly increased glucosuria without altering proximal sodium handling or evidence of sympathetic activation. Acute decreases in arterial stiffness (carotid augmentation index, −3.5%; 95% CI, −6.0 to −1.1) were observed in the dapagliflozin group after 12 weeks, although this was not significant compared with placebo. Dapagliflozin was generally safe and well tolerated. No episodes of urinary tract or genitourinary infections were observed in either treatment group throughout the trial. Conclusions: Dapagliflozin activated expected physiologic pathways, although key differences observed in KTR might suggest mechanistic heterogeneity compared with nontransplant populations. Clinical trials evaluating sodium-glucose cotransporter-2 inhibitors in KTR are important to determine whether these mechanistic effects translate to improvements in kidney and cardiovascular outcomes. Clinical Trial registry name and registration number: ClinicalTrials.gov, NCT04965935. Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3//www.asn-online.org/media/podcast/JASN/2026_02_09_KTS_February2026.mp3

Introduction: People with type 2 diabetes (T2DM) have an elevated risk of adverse outcomes from COVID-19. Dipeptidyl peptidase-4 inhibitors (DPP4is) and glucagon-like peptide-1 receptor agonists (GLP1RAs) might have favorable effects on COVID-19 outcomes. Research design and methods: We conducted a population-based cohort study in Ontario, Canada. We compared the risk of both COVID-19 infection as well as adverse outcomes between users of DPP4i or GLP1RA and users of sodium-glucose cotransporter-2 inhibitors (SGLT2is) or sulfonylureas (SUs). The study population was persons ≥66 years with T2DM taking metformin who had ≥1 COVID-19 PCR test between January 2020 and July 2021. We compared (1) COVID-19 infection and (2) adverse outcomes at 30 days among COVID-19 positive patients (major cardiovascular (CV) events, hospitalizations, intensive care unit admission, all-cause mortality, venous thromboembolism, mechanical ventilation). We reported weighted risk differences (RDs) and relative risks (RRs). Results: There were 26,485 DPP4i/GLP1RA users (mean age 76, 47% female, 91% DPP4i users) and 14,487 SGLT2i/SU users (mean age 75, 39% female, 65% SGLT2i users). The weighted rate of COVID-19 infection in DPP4i/GLP1RA users was 10.3% compared with 10.4% among SGLT2i/SU users (weighted RD −0.06, 95% CI −0.79 to 0.66; RR 0.99, 95% CI 0.93 to 1.07). Among COVID-19 positive patients, the weighted RD for all-cause hospitalization for DPP4i/GLP1RA users versus SGLT2i/SU users was −6.72% (95% CI −3.02 to −10.4) and the adjusted weighted RR was 0.79 (95% CI 0.70 to 0.89). For major CV events, the weighted RD was −1.91% (95% CI −4.00 to 0.18) and RR 0.73 (95% CI 0.54 to 1.00). Conclusions: DPP4i/GLP1RA use was not associated with reduced risk of COVID-19 infection compared with SGLT2i/SU use. DPP4i/GLP1RA use was associated with reduced risk of 30-day hospitalization among COVID-19 positive older adults and a possible trend towards a lower associated risk of CV events.

Background: Educational attainment level (EAL) is an indicator of socioeconomic status and has been shown to be inversely related with adverse health outcomes. However, the association between EAL and risk of clinical outcomes in high‐risk patients with cardiovascular disease has not been extensively investigated. Methods: In the INVESTED (Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure) trial, patients with recent heart failure or myocardial infarction hospitalization were randomized 1:1 to high‐dose trivalent or standard‐dose quadrivalent influenza vaccine from September 2016 to January 2019. We examined the association between EAL and risk of clinical outcomes for each participant across all enrolling seasons using adjusted Cox models stratified by trial entry season. Participants were categorized by EAL (≤high school, post‐high school or trade, and ≥college). Results: Of the 4912 participants (mean age: 65.5 years, 28% female, 80% White) with EAL information, 43% had high school, 29% had post‐high school or trade, and 28% had ≥college as EAL. Those with higher EAL were more likely to be White or Asian, be married/with long‐term partner, have higher left ventricular ejection fraction, have lower New York Heart Association class, and less likely to have comorbidities and risk factors than those with lower EAL. During follow‐up (median: 9 months), 1706 (35%) participants experienced the composite of all‐cause death or cardiopulmonary hospitalization. Compared with high school, higher EAL was associated with a stepwise decrease in risk (post‐high school or trade: hazard ratio [HR], 0.88 [95% CI, 0.79–0.99]; ≥college: HR, 0.71 [95% CI, 0.63–0.81], P _trend <0.001). Conclusions: High EAL is significantly associated with a decreased risk of adverse clinical outcomes in patients with high‐risk cardiovascular disease after adjustment for other key risk factors, highlighting the need to consider EAL in risk assessment and target additional resources toward those with low EAL to improve prognosis. Registration: URL: https://clinicaltrials.gov ; Unique identifier: NCT02787044.