Incremental value of C-reactive protein to the MEESSI acute heart failure risk score.

AIMS: We hypothesized that the current gold standard for risk stratification of patients with acute heart failure (AHF), the Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF (MEESSI-AHF) risk score, can be further improved by adding systemic inflammation as quantified by C-reactive protein (CRP). METHODS AND RESULTS: In a prospective multicentre diagnostic study (BASEL V), AHF was centrally adjudicated by two independent cardiologists. The MEESSI-AHF risk score was calculated using an established reduced and recalibrated model containing 12 independent risk factors. Model extension was performed by refitting and adding CRP in the logistic regression model with 30-day mortality as binary outcome. Discrimination, calibration and clinical usefulness were used to assess the performance of the extended Multiple Estimation of risk based on the Emergency department Spanish Score In patients (MEESSI) model. Validation was performed in an independent, retrospective and single-centre AHF cohort. Among 1208 AHF patients with complete data allowing calculation of the recalibrated MEESSI and the extended MEESSI models, the prognostic accuracy for 30-day mortality of the extended MEESSI model (c-statistic 0.83, 95% confidence interval [CI] 0.79-0.87) was significantly higher compared to the recalibrated model (c-statistic 0.79, 95% CI 0.75-0.83, p = 0.013). The extended model allowed to stratify a higher percentage of patients into the lowest risk group compared to the recalibrated model (33.1% vs. 20.3%). Demonstrating a calibration plot's slope of 1.00 (95% CI 0.81-1.19) and an intercept of 0.0 (95% CI -0.22 to 0.22), the extended MEESSI model achieved excellent and improved calibration. Results were confirmed in the independent validation cohort (n = 575). CONCLUSIONS: Quantifying inflammation using CRP concentration provided incremental value in AHF risk stratification using the established MEESSI model.

Quantifying Hemodynamic Cardiac Stress and Cardiomyocyte Injury in Normotensive and Hypertensive Acute Heart Failure.

BACKGROUND: The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments. METHODS: The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90-140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324). RESULTS: In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611-1956) versus 827 (448-1419) pg/mL, and 5890 (2959-12,162) versus 4068 (1986-8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24-71) versus 33 (19-59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31-2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort. CONCLUSION: Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.

Digoxin initiation after an acute heart failure episode and its association with post-discharge outcomes: an international multicenter analysis.

Digoxin is commonly used to treat acute heart failure (AHF), especially in patients with concurrent atrial fibrillation (AF). Nonetheless, there is little consensus about in which patients digoxin should be given, the proper time for digoxin initiation, and whether digoxin initiation is associated with improved outcomes. We investigated factors related to digoxin initiation after an episode of AHF and whether patients receiving digoxin presented better short-term outcomes. We analyzed digoxin-naïve AHF patients from a Spanish and Swiss database, who were dichotomized into cohorts based on their receipt of digoxin treatment at discharge. The relationship between digoxin initiation and 23 additional patient covariates, including chronic treatment, was investigated, as well as its association with 90-day combined adverse events (defined as all-cause death or AHF hospitalization). Of 13,105 patients (10,600/2505 from the Spanish/Swiss cohorts, respectively), the median (interquartile range) age was 83 (74.87) years, and 51% were women. Of these, 484 (3.7%) received digoxin at discharge, which was associated with AF, female sex, left ventricular ejection fraction (LVEF) < 50%, and coming from the Spanish cohort. Parameters inversely associated with receiving digoxin at discharge included some chronic treatments, diabetes mellitus (DM), and chronic kidney disease (CKD). Digoxin initiation was not association with 90-day adverse events, adjusted hazard ratio (aHR) = 0.939 (0.769-1.146), but there was an interaction for CKD, aHR = 1.390 (0.831-2.325) vs. 0.854 (0.682-1.183), p = 0.039, and for cohort pertinence, with higher risk in the Swiss cohort; aHR = 1.405 (0.827-2.386) vs. 0.862 (0.689-1.077), p = 0.046. Digoxin initiation after an AHF episode was more frequent in the Spanish cohort and was associated with certain patient characteristics (AF, female sex, reduced LVEF, no DM, no CKD), but had no effect on 90-day outcomes.

Prognostic Value of Self-Reported Subjective Exercise Capacity in Patients With Acute Dyspnea.

Background: Self-reported exercise capacity is a well-established prognostic measure in stable ambulatory patients with cardiac and pulmonary disease. Objectives: The authors aimed to directly compare the prognostic accuracy of quantified self-reported exercise capacity using the Duke Activity Status Index (DASI) with the established objective disease-severity marker B-type natriuretic peptide (BNP) in patients presenting with acute dyspnea to the emergency department. Methods: The DASI was obtained in a prospective multicenter diagnostic study recruiting unselected patients presenting with acute dyspnea to the emergency department. The prognostic accuracy of DASI and BNP for 90-day and 720-day all-cause mortality was evaluated using C-index. Results: Among 1,019 patients eligible for this analysis, 75 (7%) and 297 (29%) patients died within 90 and 720 days after presentation, respectively. Unadjusted hazard ratios (HRs) and multivariable adjusted hazard ratios (aHRs) for 90- and 720-day mortality increased continuously from the fourth (best self-reported exercise capacity) to the first DASI quartile (worst self-reported exercise capacity). For 720-day mortality the HR of the first quartile vs the fourth was 9.1 (95% CI, 5.5-14.9) vs (aHR: 6.1, 95% CI: 3.7-10.1), of the second quartile 6.4 (95% CI: 3.9-10.6) vs (aHR: 4.4, 95% CI: 2.6-7.3), while of the third quartile the HR was 3.2 (95% CI: 1.9-5.5) vs (aHR: 2.4, 95% CI: 1.4-4.0). The prognostic accuracy of the DASI score was high, and higher than that of BNP concentrations (720-day mortality C-index: 0.67 vs 0.62; P = 0.024). Conclusions: Quantification of self-reported subjective exercise capacity using the DASI provides high prognostic accuracy and may aid physicians in risk stratification. (Basics in Acute Shortness of Breath EvaLuation [BASEL V] Study [BASEL V]; NCT01831115).