Mittregionales Pro-Atriales Natriuretisches Peptid als Teil einer dualen Biomarker-Strategie für den früheren Ausschluss des akuten Koronarsyndroms ohne ST-Strecken-Hebung

Background: Mr-proANP is a biomarker produced in atrial and left ventricular myocardium. We investigated the effect of combined measurement of mr-proANP and high-sensitive cardiac Troponin I assay of the penultimate generation (s-cTnI) for an early type-1 and type-2 NSTE-ACS rule-out with emphasis on the very early presenters' subgroup with symptom onset time (SOT) ≤ 2 h. Methods: This was a prospective cohort study of 311 consecutive patients admitted to ER with symptoms suggestive of an acute coronary syndrome (ACS). All patients had baseline mr-proANP and s-cTnI measurements. Results: Of the total cohort, 17.6% (n = 55) had final diagnosis of NSTE-ACS: 9.6% (n = 30) had an angiographically-confirmed type-1 infarction and 8.0% (n = 25) had type-2 infarction. In the subgroup of very early presenters (SOT ≤ 2 h) the negative predictive value (NPV) of s-cTnI for type-1 NSTEACS was 96.7% (95%-CI: 87.5–99.4) and the NPV of mr-proANP was 100% (95%-CI: 87.1–100). The dual biomarker strategy yielded an NPV of 100% (95%-CI: 86.7–100). In the same time-related subgroup, the NPV of s-cTnI alone for type-2 was 98.3% (95%-CI: 89.8–99.9) and the NPV of mr-proANP was 97.0% (95%-CI: 82.5–100). The combination of biomarker increased the NPV to 100% (95%-CI: 86.7–100). Conclusions: Our study demonstrated an immediate release pattern of mr-proANP in NSTE-ACS that may bridge the silent troponin time phenomenon when highest-sensitivity cardiac troponin assays are not used. This concept performed best in the very early presenters' subgroup with an excellent NPV of 100% and might result in an early rule-out of NSTE-ACS thus accelerating the diagnostic work-up.Mr-proANP ist ein Biomarker, der im atrialen und linksventrikulären Myokard produziert wird. Wir haben den Effekt der kombinierten Messung von mr-proANP und hochsensitivem kardialen Troponin I der vorletzten Generation (s-cTnI) für einen früheren Ausschluss vom NSTE-ACS Typ-1 und Typ- 2 untersucht mit Akzentsetzung auf jene Patienten, die sich sehr früh nach Symptombeginn (≤ 2 h) in der Notaufnahme vorstellten. Methoden: Es handelte sich um eine prospektive Kohortenstudie von 311 hintereinander kommenden Patienten, die sich in der Notaufnahme mit Symptomen, die auf ein akutes Koronarsyndrom (ACS) hindeuteten, vorstellten. Bei allen Patienten fand die Bestimmung von mr-proANP- und s-cTnI-Spiegel unmittelbar nach dem Eintreffen in der Notaufnahme statt. Ergebnisse: Von der Gesamtkohorte hatten 55 (17,6%) Patienten die endgültige Diagnose eines NSTE-ACS, 30 (9,6%) Patienten hatten einen angiographisch bestätigten Typ-1-Infarkt und 25 (8,0%) Patienten hatten einen Typ-2-Infarkt. In der Subgruppe der Patienten, die sich sehr früh nach Symptombeginn (SOT ≤ 2 h) vorstellten, betrug der negative prädiktive Wert (NPW) von s-cTnI für Typ-1-NSTE-ACS 96,7% (95% -CI: 87,5–99,4) und der NPW von mr-proANP 100% (95% -CI: 87,1–100). Die duale Biomarker-Strategie erbrachte einen NPW von 100% (95% -CI: 86,7–100). In derselben Subgruppe betrug der NPW von s-cTnI allein für Typ-2 98,3% (95% -CI: 89,8–99,9), der NPW von mr-proANP betrug 97,0% (95% -CI: 82,5– 100). Die Kombination zweier Biomarker erhöhte den NPW auf 100% (95% -CI: 86,7–100). Schlussfolgerungen: Unsere Studie zeigte ein sofortiges Freisetzungsmuster von mr-proANP in NSTE-ACS, was möglicherweise das Phänomen der „silent troponin time“ überbrücken könnte, wenn keine Herz-Troponin-Assays mit höchster Empfindlichkeit verwendet werden. Dieses Konzept erzielte in der Gruppe der Patienten, die sich sehr früh nach Symptombeginn vorstellten, einen NPW von 100%. Somit könnte ein früherer Ausschluss von NSTE-ACS erzielt werden, wodurch die gesamte diagnostische Aufarbeitung beschleunigt werden könnte

Is 24/7 remote patient management in heart failure necessary? Results of the telemedical emergency service used in the TIM‐HF and in the TIM‐HF2 trials

Aims: Telemedical emergency services for heart failure (HF) patients are usually provided during business hours. However, many emergencies occur outside of business hours. This study evaluates if a 24/7 telemedical emergency service is needed for the remote management of high-risk HF patients. Methods: and results The study included 1119 patients merged from the TIM-HF and TIM-HF2 trials [age 69 +/- 11, 73% male, left ventricular ejection fraction 37% +/- 13, 557 New York Heart Association (NYHA) II/562 NYHA III]. Patients received a 24/7 physician-guided emergency service provided by the telemedical centre (TMC) in addition to remote management within business hours. During emergency calls, patient status, symptoms, electronic patient record, and instant telemonitoring data were evaluated by the TMC physician. Following diagnosis, patients were referred for hospital admission or instructed to stay at home. Apart from the TMC, patients could place a call to the public emergency service at any time. Seven hundred sixty-eight emergency calls were placed over 1383 patient years (0.56 calls/patient year). Five hundred twenty-six calls (69%) occurred outside business hours. There were 146 (19%) emergency calls for worsening HF, 297 (39%) other cardiovascular, and 325 (42%) non-cardiac causes, with a similar pattern inside and outside business hours. Of the 1119 patients, 417 (37%) placed at least one emergency call. Patients with NYHA Class III, higher N-terminal prohormone of brain natriuretic peptide (>1.400 pg/mL) levels, ischaemic aetiology of HF, implanted defibrillator, and impaired renal function had a higher probability of placing emergency calls. During study follow-up, patients who made an emergency call had a higher all-cause mortality (22% vs. 11%, P = 0.007 in TIM-HF; 16% vs. 4%, P < 0.001 in TIM-HF2) and more unplanned hospitalizations (324 vs. 162, P < 0.001 in TIM-HF; 545 vs. 180, P < 0.001 in TIM-HF2). Of the total 1,211 unplanned hospital admissions, 492 (41%) were initiated by a patient emergency call. Three hundred seventy-nine calls (49%) were placed to the TMC, whereas 389 calls (51%) were made to the public emergency service. Three hundred twenty-six (84%) of the calls to the public emergency service resulted in acute hospitalizations. The TMC initiated 202 (53%) hospital admissions; 177 (47%) patients were advised to stay at home. All patients that remained at home were alive during a prespecified safety period of 7 days post-call. Diagnoses made by the TMC physician were confirmed in 83% of cases by the hospital. Conclusion: A telemedical emergency service for high-risk HF patients is safe and should operate 24/7 to reduce unplanned hospitalizations. Emergency calls could be considered as a marker for higher morbidity and mortality

Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): a randomized, controlled clinical process study

Aims This randomized controlled trial (RCT) evaluated whether a process with single combined testing of copeptin and troponin at admission in patients with low-to-intermediate risk and suspected acute coronary syndrome (ACS) does not lead to a higher proportion of major adverse cardiac events (MACE) than the current standard process (non-inferiority design). Methods and results A total of 902 patients were randomly assigned to either standard care or the copeptin group where patients with negative troponin and copeptin values at admission were eligible for discharge after final clinical assessment. The proportion of MACE (death, survived sudden cardiac death, acute myocardial infarction (AMI), re-hospitalization for ACS, acute unplanned percutaneous coronary intervention, coronary artery bypass grafting, or documented life threatening arrhythmias) was assessed after 30 days. Intention to treat analysis showed a MACE proportion of 5.17% [95% confidence intervals (CI) 3.30-7.65%; 23/445] in the standard group and 5.19% (95% CI 3.32-7.69%; 23/443) in the copeptin group. In the per protocol analysis, the MACE proportion was 5.34% (95% CI 3.38-7.97%) in the standard group, and 3.01% (95% CI 1.51-5.33%) in the copeptin group. These results were also corroborated by sensitivity analyses. In the copeptin group, discharged copeptin negative patients had an event rate of 0.6% (2/362). Conclusion After clinical work-up and single combined testing of troponin and copeptin to rule-out AMI, early discharge of low- to intermediate risk patients with suspected ACS seems to be safe and has the potential to shorten length of stay in the ED. However, our results need to be confirmed in larger clinical trials or registries, before a clinical directive can be propagate

Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): a randomized, controlled clinical process study

Aims: This randomized controlled trial (RCT) evaluated whether a process with single combined testing of copeptin and troponin at admission in patients with low-to-intermediate risk and suspected acute coronary syndrome (ACS) does not lead to a higher proportion of major adverse cardiac events (MACE) than the current standard process (non-inferiority design). Methods and results: A total of 902 patients were randomly assigned to either standard care or the copeptin group where patients with negative troponin and copeptin values at admission were eligible for discharge after final clinical assessment. The proportion of MACE (death, survived sudden cardiac death, acute myocardial infarction (AMI), re-hospitalization for ACS, acute unplanned percutaneous coronary intervention, coronary artery bypass grafting, or documented life threatening arrhythmias) was assessed after 30 days. Intention to treat analysis showed a MACE proportion of 5.17% [95% confidence intervals (CI) 3.30–7.65%; 23/445] in the standard group and 5.19% (95% CI 3.32–7.69%; 23/443) in the copeptin group. In the per protocol analysis, the MACE proportion was 5.34% (95% CI 3.38–7.97%) in the standard group, and 3.01% (95% CI 1.51–5.33%) in the copeptin group. These results were also corroborated by sensitivity analyses. In the copeptin group, discharged copeptin negative patients had an event rate of 0.6% (2/362). Conclusion: After clinical work-up and single combined testing of troponin and copeptin to rule-out AMI, early discharge of low- to intermediate risk patients with suspected ACS seems to be safe and has the potential to shorten length of stay in the ED. However, our results need to be confirmed in larger clinical trials or registries, before a clinical directive can be propagated