Risk Differences in Secondary Prevention Patients Who Present With Acute Coronary Syndrome and Implications of Guideline-Directed Cholesterol Management.

The 2018 American College of Cardiology/American Heart Association cholesterol guidelines for secondary prevention identified a group of "very high risk" (VHR) patients, those with multiple major atherosclerotic cardiovascular disease (ASCVD) events or 1 major ASCVD event with multiple high-risk features. A second group, "high risk" (HR), was defined as patients without any of the risk features in the VHR group. The incidence and relative risk differences of these 2 groups in a nontrial population has not been well characterized. Using the Northwestern Medicine Enterprise Data Warehouse, we compared the incidence of VHR and HR patients as well as their relative risk for cardiovascular morbidity and mortality in a single-center, large, academic, retrospective cohort study. Total 1,483 patients with acute coronary events from January 2014 to December 2016 were risk stratified into VHR and HR groups. International Classification of Diseases versions 9 and 10 were used to assess for composite events of unstable angina pectoris, non-ST elevation myocardial infarction, or ST-elevation myocardial infarction, ischemic stroke, or all-cause death with a median follow-up of 3.3 years. VHR patients were found to have 87 ± 5.4 composite events per 1,000 patient-years compared with HR patients who had 33 ± 5.1 events per 1,000 patient-years (p <0.001). VHR group had increased risk of future events as compared to the HR group (multivariable adjusted hazard ratio 1.66 [1.01 to 2.74], p = 0.047). In conclusion, these results support the stratification of patients into the VHR and HR risk groups for secondary prevention.

Acquired Methemoglobinemia Associated with Topical Lidocaine Administration: A Case Report.

A 55-year-old male was admitted to the hospital with pneumonia. During an intubation procedure, the patient received an application of endobronchial lidocaine (4% gel). Within 2 h of intubation, the patient developed worsening hypoxia, and investigation of arterial blood gasses revealed a pH of 7.21, carbon dioxide partial pressure (PaCO2) of 3.3 kPa, oxygen partial pressure (PaO2) of 55.1 kPa, and measured oxygen saturation of 49%. Co-oximetry of this sample returned a methemoglobin level of 53%. Intravenous methylthioninium chloride (1% solution at 1 mg/kg) was delivered, and subsequent arterial blood gasses, at 30 min and 1 h post administration, showed methemoglobin levels of 12 and 9%, respectively, with return of oxygen saturation to > 90%.

Treatment of established left ventricular hypertrophy with fibroblast growth factor receptor blockade in an animal model of CKD.

BACKGROUND: Activation of fibroblast growth factor receptor (FGFR)-dependent signalling by FGF23 may contribute to the complex pathogenesis of left ventricular hypertrophy (LVH) in chronic kidney disease (CKD). Pan FGFR blockade by PD173074 prevented development of LVH in the 5/6 nephrectomy rat model of CKD, but its ability to treat and reverse established LVH is unknown. METHODS: CKD was induced in rats by 5/6 nephrectomy. Two weeks later, rats began treatment with vehicle (0.9% NaCl) or PD173074, 1 mg/kg once-daily for 3 weeks. Renal function was determined by urine and blood analyses. Left ventricular (LV) structure and function were determined by echocardiography, histopathology, staining for myocardial fibrosis (Sirius-Red) and investigating cardiac gene expression profiles by real-time PCR. RESULTS: Two weeks after inducing CKD by 5/6 nephrectomy, rats manifested higher (mean ± SEM) systolic blood pressure (208 ± 4 versus 139 ± 3 mmHg; P < 0.01), serum FGF23 levels (1023 ± 225 versus 199 ± 9 pg/mL; P < 0.01) and LV mass (292 ± 9 versus 220 ± 3 mg; P < 0.01) when compared with sham-operated animals. Thereafter, 3 weeks of treatment with PD173074 compared with vehicle did not significantly change blood pressure, kidney function or metabolic parameters, but significantly reduced LV mass (230 ± 14 versus 341 ± 33 mg; P < 0.01), myocardial fibrosis (2.5 ± 0.7 versus 5.4 ± 0.95% staining/field; P < 0.01) and cardiac expression of genes associated with pathological LVH, while significantly increasing ejection fraction (18 versus 2.5% post-treatment increase; P < 0.05). CONCLUSIONS: FGFR blockade improved cardiac structure and function in 5/6 nephrectomy rats with previously established LVH. These data support FGFR activation as a potentially modifiable, blood pressure-independent molecular mechanism of LVH in CKD.