Background: To investigate the individual profile of each SGLT2 (sodium‐glucose cotransoporter‐2) inhibitor in patients with different backgrounds. Methods and Results: This study included 21 placebo‐controlled randomized controlled trials with a total of 96 196 participants, investigating empagliflozin, ertugliflozin, dapagliflozin, canagliflozin, and sotagliflozin. The primary efficacy end point was the composite of cardiovascular death and hospitalizations for heart failure. The secondary efficacy end points were all‐cause death, cardiovascular death, hospitalizations for heart failure, kidney disease progression, and acute kidney injury. We conducted subgroup analyses based on the underlying comorbidities, including diabetes and chronic kidney disease. Safety end points were also assessed among SGLT2 inhibitors in the overall cohort. In the overall cohort, there were no significant differences in the primary efficacy outcome among the SGLT2 inhibitors, while empagliflozin (hazard ratio [HR], 0.70 [95% CI, 0.53–0.92]) and dapagliflozin (HR, 0.73 [95% CI, 0.56–0.96]) were associated with lower risk of acute kidney injury than sotagliflozin. The presence or absence of diabetes did not alter the results. In patients with chronic kidney disease, there were no differences in the efficacy outcomes among SGLT2 inhibitors, while in patients without chronic kidney disease, empagliflozin was associated with lower risk of the primary outcome compared with ertugliflozin (HR, 0.77 [95% CI, 0.60–0.98]). For safety outcomes, no significant differences were observed in amputation, urinary tract infection, genital infection, hypoglycemia, and diabetic ketoacidosis. Conclusions: The differences in reducing cardiovascular and kidney outcomes as well as safety profiles across SGLT2 inhibitors were not consistently significant, although empagliflozin might be preferred in patients without chronic kidney disease. Further investigations are needed to better understand the mechanism and clinical effectiveness of each SGLT2 inhibitor in certain populations.

The COVID-19 global pandemic began in December 2019.¹ The introduction of the messenger RNA (mRNA) vaccine against SARS-CoV-2 has resulted in a significant decline in COVID-19–related morbidity and mortality all over the world.^2-4 COVID-19 mRNA vaccines are the current standard approach to contain the pandemic and the Emergency Use Authorizations for these vaccines were recently extended to children aged 6 months and older in the US. Since the emergency use was authorized, the association of the mRNA-based COVID-19 vaccine with myopericarditis, which is a rare but serious adverse event, has been reported.^5,6 Cases of myopericarditis following COVID-19 mRNA vaccination have been reported worldwide, especially in adolescents and young adults. In addition, in June 2021, the Centers for Disease Control and Prevention (CDC) observed a rate of postvaccine myopericarditis that was higher in young males after the second mRNA vaccine doses.⁷ Previous studies reported largely favorable outcomes in adults with myocarditis following COVID-19 mRNA vaccination, demonstrating resolution of clinical symptoms, preservation of cardiac function, and no complications.^8-11 However, data on the clinical features and outcomes of myopericarditis after COVID-19 vaccination in adolescents and young adults are scarce compared with adults and often consist of small case series. Most large-scale studies on COVID-19 vaccine–associated myopericarditis among adolescents and young adults are derived from national population-based studies that contain homogeneous populations or from surveillance networks that rely on passive reporting. In this study, we conducted a systematic review and meta-analysis to investigate the clinical spectrum and outcomes of COVID-19 vaccine–associated myopericarditis in adolescents and young adults from an international population.

Diastolic dysfunction is important in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Sympathetic nervous hyperactivity may contribute to the development of diastolic dysfunction. The aim of this study was to determine the relationship between myocardial sympathetic innervation quantified by ¹¹C-hydroxyephedrine PET and diastolic dysfunction in HFpEF patients. Methods: Forty-one HFpEF patients having an echocardiographic left ventricular ejection fraction of 40% or greater and 12 age-matched volunteers without heart failure underwent the echocardiographic examination and ¹¹C-hydroxyephedrine PET. Diastolic dysfunction was classified into grades 0–3 by Doppler echocardiography. Myocardial sympathetic innervation was quantified using the ¹¹C-hydroxyephedrine retention index (RI). The coefficient of variation of 17-segment RIs was derived as a measure of heterogeneity in myocardial ¹¹C-hydroxyephedrine uptake. Results: Grade 2–3 diastolic dysfunction (DD_2–3) was found in 19 HFpEF patients (46%). They had a significantly lower global RI (0.075 ± 0.018 min⁻¹) than volunteers (0.123 ± 0.028 min⁻¹, P < 0.001) and HFpEF patients with grade 0–1 diastolic dysfunction (DD_0–1) (0.092 ± 0.024 min⁻¹, P = 0.046). HFpEF patients with DD_2–3 had the largest coefficient of variation of 17-segment RIs of the 3 groups (18.4% ± 7.7% vs. 14.1% ± 4.7% in HFpEF patients with DD_0–1, P = 0.042 for post hoc tests). In multivariate logistic regression analysis, a lower global RI (odds ratio, 0.66 per 0.01 min⁻¹; 95% confidence interval, 0.38–0.99; P = 0.044) was independently associated with the presence of DD_2–3 in HFpEF patients. Conclusion: Myocardial sympathetic innervation was impaired in HFpEF patients and was associated with the presence of advanced diastolic dysfunction in HFpEF.