BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). METHODS: Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro–B-type natriuretic peptide) was an exploratory end point. RESULTS: A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (N=187) or enalapril (N=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47–0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72–1.14]; P =0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. CONCLUSIONS: In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02678312.

Vascular complications are the leading causes of reduced life quality and mortality in type 2 diabetes mellitus (T2DM). Life's Essential 8 (LE8) is a newly modified measurement of cardiovascular health (CVH) by American Heart Association (AHA). Promoting CVH has been previously shown to improve the prognosis of T2DM. However, studies regarding the effects of CVH by LE8 on diabetic retinopathy (DR), a major microvascular complication, and death from the cardiovascular and overall causes in T2DM are currently lacking. This study aimed to investigate these associations thus providing preliminary evidence. A total of 3192 participants from the National Health and Nutrition Examination Survey (NHANES) were included in the final analysis. Records of mortality during follow-up were obtained by linking to the National Death Index. The multivariable logistic regression and Cox proportional hazard regression with restricted cubic splines were used to estimate the associations. Subgroup analyses were performed to examine the effects of gender, age, and duration of T2DM. 648 individuals had DR at baseline. During a median follow-up of 76 months, 645 overall deaths (incidence per 1000 person-years, 26.53%; 95% confidence interval (CI), 26.50-26.56) were ascertained, including 216 from cardiovascular causes (incidence per 1000 person-years, 8.96%; 95% CI, 8.94-8.98). The multivariable-adjusted odds ratio (OR) per 100-point increase of LE8 was 0.80 (95% CI, 0.71-0.90) for DR, and participants with high levels of LE8 were associated with 47% risk reduction (OR, 0.53; 95% CI, 0.40-0.70). The multivariable-adjusted hazard ratio (HR) per 100-point increase of LE8 was 0.71 (95% CI, 0.62-0.81) and 0.68 (95% CI, 0.58-0.85) for all-cause mortality and cardiovascular mortality, respectively. Similar patterns of inverse associations were observed in participants with moderate and high levels of LE8 for all-cause and cardiovascular mortality. Notably, stronger associations between LE8 and mortality were discovered in participants below 60 years (P < 0.05 for interaction). Moreover, LE8 was correlated with all-cause mortality in a linear way (P for nonlinear=0.32). The AHA's newly prompted LE8 was strongly and inversely associated with the risk of DR, all-cause mortality, and cardiovascular-specific mortality in T2DM. LE8 may be a feasible and effective approach in the tertiary prevention of T2DM.

Objectives: 1) To describe the postoperative course and outcomes of cardiac surgery in children with perioperative viral respiratory infection, 2) to evaluate optimal surgical timing for preoperative viral respiratory infection patients, and 3) to define risk stratification. Design: Retrospective study of children undergoing cardiac surgery. Children were tested using a multiplex polymerase chain reaction (respiratory virus polymerase chain reaction) panel capturing seven respiratory viruses. Respiratory virus polymerase chain reaction testing was routinely performed in patients under 2 years old. Those with negative results yet highly suspected of viral respiratory infection after surgeries would be tested again. Setting: A pediatric cardiac surgical ICU of pediatric cardiac surgery department at Fuwai Hospital. Patients: Children admitted between January 1, 2014, and December 31, 2016, to perform respiratory virus polymerase chain reaction testing and cardiac surgery were included. Interventions: None. Measurements and Main Results: A total of 2,831 patients had respiratory virus polymerase chain reaction testing, and viruses were detected in 91 patients (3.2%), including 35 preoperative and 56 postoperative. Of the 35 preoperative viral respiratory infection patients, there were 29 viral respiratory infection-resolved (patients for whom surgery was postponed until resolution of viral respiratory infection symptoms and negative respiratory virus polymerase chain reaction) and six viral respiratory infection-unresolved (who underwent cardiac surgery before resolution of symptoms and clearance of carriage) patients. Furthermore, there were seven deaths, including one in the preoperative viral respiratory infection-unresolved group and six in the postoperative viral respiratory infection group. A propensity score matching was performed to correct the selection bias and identify the comparable patient groups. Compared to their matched nonviral respiratory infection patients, viral respiratory infection-resolved patients had similar duration of mechanical ventilation and length of stay, while viral respiratory infection-unresolved patients had longer durations of postoperative mechanical ventilation (p = 0.033), PICU (p = 0.028) and hospital length of stay (p = 0.010), and postoperative viral respiratory infection patients had significantly greater duration of postoperative recovery (p < 0.001) and higher mortality (p < 0.001). Earlier diagnosis of postoperative viral respiratory infection was associated with longer mechanical ventilation duration (r ² = 0.422; p < 0.001). Palliative cardiac surgery was the only variable significantly associated with mortality in multivariate analysis (odds ratio, 12.0; 95% CI, 1.6–87.5; p = 0.014). Conclusions: The preoperative-unresolved and postoperative viral respiratory infection were associated with prolonged postoperative recovery, increased severity, and mortality in children with cardiac surgeries. Our results suggested the optimal surgical timing may be after the resolution of viral respiratory infection symptoms and carriage unless the perceived benefits of early surgery outweigh the risk of death, prolonged ventilation, and PICU length of stay. Palliative surgeries were associated with increasing mortality.

Introduction: Promoting cardiovascular health (CVH) by Life’s Simple 7 is associated with better cognitive function. In 2022, the American Heart Association (AHA) prompted Life’s Essential 8 (LE8) to strengthen CVH assessment. This study investigated the association between the new CVH metrics assessed by LE8 and cognitive function, thus providing evidence for implementing LE8 in the primordial prevention of cognitive impairment. Methods: 2,050 participants aged 60 and older from National Health and Nutrition Examination Survey 2011–2014 were included. Cognitive function was measured by the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). The overall and domain-specific cognitive function z-score was created. CVH score was calculated following AHA’s advisory. The multivariable linear regression model estimated the associations. Results: The CVH score assessed by LE8 was independently, positively, and linearly associated with the overall cognitive function. A per-10 point increase in CVH was associated with higher overall cognitive z-scores (β, 0.06; 95% confidence interval [CI], 0.03, 0.09), and participants with moderate (β, −0.14; 95% CI, −0.22, −0.05) and low CVH (β, −0.27; 95% CI, −0.37, −0.16) had lower overall cognitive z-scores compared to participants with high CVH. Similar patterns of associations were observed between CVH of AFT and DSST. Components of CVH were further associated with different domain-specific cognitive functions. Conclusion: Maintaining an ideal CVH improves cognitive function in older adults. Ideal adherence to individual components of LE8 was associated with improved overall and domain-specific cognitive functions. Therefore, promoting CVH according to LE8 might benefit cognitive function in the elderly.

Metabolic syndrome (MetS) could increase the risk of cardiovascular disease (CVD) by 2-fold. Ideal control of modifiable risk factors in Life's Simple 7 (LS7) could reduce the CVD risk among the general population. This study aimed to investigate the effects of controlling modifiable risk factors using LS7 in MetS to prevent CVD. 44463 participants in NHANES 1999–2018 were included. The primary endpoint was a composite of CVD, including angina pectoris, coronary artery disease, myocardial infarction, congestive heart failure, and stroke. Multivariable weighted logistic regression analyses estimated the associations. The diagnosis of MetS complied with Harmonized International Diabetes Federation Criteria. Measurement of modifiable risk factors used the 2010 American Heart Association LS7 guideline and was indicated by cardiovascular health (CVH). 14034 individuals were diagnosed with MetS. 4835 participants had CVD. The weighted mean CVH was 8.06 ± 0.03. Intermediate and poor CVH were associated with increased risk for CVD in participants with similar metabolic states compared to ideal CVH. By taking participants with metabolic health and ideal CVH as health control, participants with MetS and poor CVH were demonstrated to have a 3-fold (adjusted odds ratio, 4.00; 95 % confidence interval, 3.21–4.98) greater risk for CVD. Notably, under the condition of ideal CVH, the risk of having CVD was comparable between metabolic health and MetS after fully adjusted. Ideal control of Life's Simple 7 in metabolic syndrome contributes to a comparable risk of cardiovascular disease with healthy subjects. LS7 could be recognized as a guideline for secondary prevention in MetS.