Stella M. Macı́n

BACKGROUND: The progression of chronic heart failure (CHF) is related to ongoing myocyte loss, which can be detected by cardiac troponin T (cTnT). We examined the prevalence and prognostic value of increased cTnT concentrations in serial blood specimens from patients with severe CHF. METHODS AND RESULTS: Clinical, echocardiographic, and 6-minute walk test data were collected prospectively at baseline and at 1 year in 115 outpatients (mean age, 61+/-11 years; 75% men; 62% coronary heart disease) with CHF and a left ventricular ejection fraction <40%. Blood samples were collected at baseline and at 3, 6, and 12 months of follow-up. cTnT concentrations > or =0.02 ng/mL were considered abnormal, and a Tn index (highest cTnT measurement/0.02 ng/mL) was calculated. In 62 patients (54%), cTnT was consistently <0.02 ng/mL (group 1); 28 (24%) had a single abnormal cTnT result (group 2); and 25 (22%) had > or =2 abnormal cTnT results (group 3). At 18 months, CHF hospitalization-free survival was 63%, 46%, and 17%, respectively (P=0.0001). In a Cox proportional-hazards model, hospitalization for worsening CHF in the previous year (HR=2.1; 95% CI, 1.1 to 4.1), functional class III-IV (HR=2.3; 95% CI, 1.1 to 4.6), and number of abnormal cTnT samples (HR=1.6; 95% CI, 1.1 to 2.4) were independently associated with prognosis. A cTnT rise of 0.020 ng/mL in any sample was associated with an excess of 9% (95% CI, 1% to 18%) in the incidence of combined end point. CONCLUSIONS: Abnormal cTnT concentrations were detected in >50% of outpatients with advanced CHF. This ongoing myocardial necrosis was a strong predictor of worsening CHF, suggesting a role of cTnT-based monitoring to identify high-risk patients.

AIMS: Hyponatraemia has been associated with reduced survival in patients with heart failure and reduced ejection fraction (HF-REF). The relationship between serum sodium and outcome is unclear in heart failure with preserved (≥ 50%) ejection fraction (HF-PEF). Therefore, we used a large individual patient data meta-analysis to study the risk of death associated with hyponatraemia in HF-REF and in HF-PEF. METHODS AND RESULTS: This analysis included 14 766 patients from 22 studies that recruited patients without ejection fraction inclusion criterion at baseline and reported death from any cause. Cox proportional analysis was undertaken for hyponatraemia (sodium <135 mmol/L), adjusted for variables of clinical relevance, and stratified by study. The endpoint was death from any cause at 3 years. Patients with hyponatraemia (n = 1618) and patients with normal serum sodium had similar characteristics as regards to age, gender, and ischaemic aetiology. However, patients with hyponatraemia had higher New York Heart Association class and lower blood pressure. At follow-up, there were 335 deaths among 1618 patients with hyponatraemia (21%) and 2128 deaths among 13 148 patients with normal serum sodium (16%). The risk of death appeared to increase linearly with serum sodium levels <140 mmol/L. Hyponatraemia was identified in 1199 HF-REF patients (11%) and 419 HF-PEF patients (11%). Hyponatraemia was independently predictive of death in both HF-REF [adjusted hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.50-1.91] and HF-PEF (adjusted HR 1.40, 95% CI 1.10-1.79, P for interaction 0.20). CONCLUSION: Hyponatraemia is a powerful determinant of mortality in patients with HF regardless of ejection fraction. Further work is needed to determine if correction of hyponatraemia translates into clinical benefit.

Importance: Inflammation promotes cardiovascular disease and anti-inflammatory treatment reduces cardiovascular events in patients with chronic coronary syndrome. Chronic kidney disease (CKD) is a risk factor for cardiovascular disease. It is unclear how inflammation mediated by interleukin 6 (IL-6) in patients with CKD is linked to cardiovascular disease. Objective: To investigate associations between IL-6 and cardiovascular outcomes in patients with chronic coronary syndrome in association with kidney function. Design, Setting, and Participants: This multicenter cohort study included patients enrolled at 663 centers in 39 countries with chronic coronary syndrome who were included in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial. Patients were enrolled between December 2008 and April 2010 and were followed up for a median length of 3.7 years. Analysis in this substudy began September 2020. Exposures: Exposures were IL-6 and creatinine estimated glomerular filtration rates (eGFR), which were collected at baseline. Associations between continuous and categorical levels (<2.0 ng/L vs ≥2.0 ng/L) of IL-6 and cardiovascular outcomes were tested in association with eGFR cutoffs (normal eGFR level [≥90 mL/min/1.73 m2], mildly decreased eGFR level [60-90 mL/min/1.73 m2], and moderately to severely decreased eGFR level [<60 mL/min/1.73 m2]). Main Outcomes and Measures: Main outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke. Results: This substudy of the STABILITY trial included 14 611 patients with available IL-6 levels at baseline. The median (interquartile range) age was 65 (59-71) years, and 2700 (18.5%) were female. During follow-up, MACE occurred in 1459 individuals (10.0%). Higher levels of IL-6 were in continuous models independently associated with risk of MACE (P < .001) in all CKD strata. Using predefined strata, elevated IL-6 level (≥2.0 vs <2.0 ng/L) was associated with increased risk of MACE at normal kidney function (2.9% vs 1.9% events/y [hazard ratio, 1.35; 95% CI, 1.02-1.78]), mild CKD (3.3% vs 1.9% [hazard ratio, 1.57; 95% CI, 1.35-1.83]), and moderate to severe CKD (5.0% vs 2.9% [hazard ratio, 1.60; 95% CI, 1.28-1.99]). Conclusions and Relevance: In patients with chronic coronary syndrome, elevated levels of IL-6 were associated with risk of MACE in all CKD strata. Thus, IL-6 and CKD stage may help when identifying patients with chronic coronary syndrome for anti-inflammatory treatment.