Results
Patient Characteristics
The current analysis included a total of 1557 patients with acute dyspnoea. Table 1 shows the characteristics and diagnoses of all study patients and of the EU and USA subgroups.
Patients in the EU were significantly older than patients in the USA, had more abnormal physical examination variables and a significantly higher mortality rate. Significantly more patients were diagnosed with acute heart failure in the EU than in the USA.
More patients were primarily discharged in the USA. Figure 1 shows the distribution of original dispositions from the EDs for both continents.
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Figure 1.
Primary disposition of patients by continent. *Monitoring unit, only available in the USA. CCU, cardiac care unit; ICU, intensive care unit.
MR-proADM as a Prognostic Marker
The median MR-pro-ADM value for all patients was 0.87 (IQR 0.57/1.43) nmol/l. Values were significantly higher in the EU as compared with the USA (1.03 (IQR 0.70/1.64) vs 0.75 (0.49/1.22) nmol/l, p<0.0001). MR-pro-ADM was significantly higher in patients who died during the follow-up than in patients who survived in both continents (EU: 1.82 (IQR 1.04/3.36) vs 0.97 (0.70/1.50) nmol/l; USA: 1.27 (0.96/1.73) vs 0.74 (0.49/1.19) nmol/l, p for both <0.0001) (figure 2, detailed data available in the online supplementary Table 1). Values of patients who died were higher than those of survivors in each disposition category for both the EU and the USA (figure 3, detailed data available in the online supplementary Table 2). Patients discharged had significantly lower values than patients admitted in both continents (all p<0.0001, figure 3).
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Figure 2.
Mid-regional pro-adrenomedullin (MR-proADM) concentrations by outcome and continent.
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Figure 3.
Mid-regional pro-adrenomedullin (MR-proADM) concentration by outcome and disposition for European Union (A) and USA (B) sites. *p values comparing concentration of patients in the respective admittance category with those in the discharge group. CCU, cardiac care unit; ICU, intensive care unit.
Net Reclassification Improvement
In the USA, 33 of 831 patients died during the follow-up period, 798 patients survived the 90-day follow-up period. Table 2 shows the results of the NRI analysis for the US patients. Originally, of the 798 survivors, 329 patients were discharged, 287 were admitted to a general ward, 147 to a monitoring ward and 35 patients to an ICU. The middle section of Table 2 shows the disposition changes after including the MR-proADM result. All 329 patients who survived the follow-up period and who were originally discharged would also be discharged when applying the MR-proADM model. Of the 287 survivors who were originally admitted to a general ward, 55 would be downgraded (to a lower level of care, ie, discharge) and two would be upgraded (to a higher level of care ie, monitoring unit), while 230 patients would have remained at this level of care. Of the 147 survivors who were originally admitted to a monitoring unit, 16 would be downgraded to a general ward and two upgraded to a CCU/ICU, 129 patients would have stayed at this level of care. Of the 35 survivors who were originally admitted to a CCU/ICU, five would be downgraded to a monitoring unit. Of the 33 non-survivors, only one patient would be upgraded from monitoring unit to ICU, all other non-survivors would have remained at their original disposition level (Table 2). Thus 76 (9.5%) of the survivors were downgraded and 4 (0.5%) upgraded while only one non-survivor (3%) changed disposition (upgrade from monitoring unit to ICU). The overall NRI as defined by Pencina et al as the sum of the two rates in the USA is therefore 12.0% (95% CI 5.7% to 18.4%). A total of n=81 (11.2%) patients changed disposition.
In Europe, 87 of 726 patients died during the follow-up period. Application of the MR-pro ADM model meant that of the survivors, all 189 who were originally discharged remained at this disposition level, of the 395 patients originally admitted to a general ward, 30 were downgraded to discharge and five upgraded to a CCU/ICU. Of the 55 CCU/ICU patients 26 were downgraded to a general ward. The four non-survivers who were originally discharged stayed at this disposition level, of the 65 patients originally admitted to a general ward nine patients were upgraded to a CCU/ICU and of the 18 patients originally admitted to a CCU/ICU two were downgraded to a general ward (Table 3). The overall NRI in the EU is 16.0% (95% CI 8.2% to 23.9%), or 56 (9%) downgrades and 5 (1%) upgrades among the survivors, 2 (2%) downgrades and 9 (10%) upgrades among non-survivors. A total of n=72 (9.9%) patients changed disposition.
Following this analysis, the number of CCU/ICU admissions in the EU would be reduced by n=14 (19.2%), and the number of admissions to the general ward by n=16 (3.5%). Overall, 30 additional patients would have been discharged (increase of 15.5%).
In the USA, the number of ICU admissions would reduce by n=2 (4.9%), the number of monitored bed admissions by n=12 (7.6%), and the number of admissions to the general ward by n=41 (13.7%). Overall, 55 additional patients would have been discharged (increase of 16.5%).