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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.
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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.
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BACKGROUND: The high-sensitivity cardiac troponin (hs-cTn) I point-of-care (POC) hs-cTnI-PATHFAST assay has recently become clinically available. METHODS: We aimed to externally validate the hs-cTnI-PATHFAST 0/1h-algorithm recently developed for the early diagnosis of non-ST-segment-elevation myocardial infarction (NSTEMI) and derive and validate a 0/2-algorithm in patients presenting to the emergency department with acute chest discomfort included in a multicenter diagnostic study. Two independent cardiologists centrally adjudicated the final diagnoses using all the clinical and study-specific information available including serial measurements of hs-cTnI-Architect. RESULTS: Among 1,532 patients (median age 60 years, 33% [n = 501] women), NSTEMI was the final diagnosis in 13%. External validation of the hs-cTnI-PATHFAST 0/1h-algorithm showed very high negative predictive value (NPV; 100% [95%CI, 99.5%-100%]) and sensitivity 100% (95%CI, 98.2%-100%) for rule-out of NSTEMI. Positive predictive value (PPV) and specificity for rule-in of NSTEMI were high (74.9% [95%CI, 68.3%-80.5%] and 96.4% [95%CI, 95.2%-97.3%], respectively). Among 1,207 patients (median age 61 years, 32% [n = 391] women) available for the derivation (n = 848) and validation (n = 359) of the hs-cTnI-PATHFAST 0/2h-algorithm, a 0h-concentration <3 ng/L or a 0h-concentration <4 ng/L with a 2h-delta <4ng/L ruled-out NSTEMI in 52% of patients with a NPV of 100% (95%CI, 98-100) and sensitivity of 100% (95%CI, 92.9%-100%) in the validation cohort. A 0h-concentration ≥90ng/L or a 2h-delta ≥ 55ng/L ruled-in 38 patients (11%): PPV 81.6% (95%CI, 66.6-90.8), specificity 97.7% (95%CI, 95.4-98.9%). CONCLUSIONS: The POC hs-cTnI-PATHFAST assay allows rapid and effective rule-out and rule-in of NSTEMI using both a 0/1h- and a 0/2h-algorithm with high NPV/sensitivity for rule-out and high PPV/specificity for rule-in. CLINICAL TRIAL REGISTRATION: NCT00470587.
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Infarto del Miocardio , Infarto del Miocardio sin Elevación del ST , Infarto del Miocardio con Elevación del ST , Humanos , Femenino , Persona de Mediana Edad , Infarto del Miocardio sin Elevación del ST/diagnóstico , Sistemas de Atención de Punto , Infarto del Miocardio/diagnóstico , Estudios Prospectivos , Biomarcadores , Troponina I , Algoritmos , Troponina TRESUMEN
AIMS: Sex-specific differences in acute heart failure (AHF) are both relevant and underappreciated. Therefore, it is crucial to evaluate the risk/benefit ratio and the implementation of novel AHF therapies in women and men separately. METHODS AND RESULTS: We performed a pre-defined sex-specific analysis in AHF patients randomized to a strategy of early intensive and sustained vasodilatation versus usual care in an international, multicentre, open-label, blinded endpoint trial. Inclusion criteria were AHF with increased plasma concentrations of natriuretic peptides, systolic blood pressure ≥100 mmHg, and plan for treatment in a general ward. Among 781 eligible patients, 288 (37%) were women. Women were older (median 83 vs. 76 years), had a lower body weight (median 64.5 vs. 77.6 kg) and lower estimated glomerular filtration rate (median 48 vs. 54 ml/min/1.73 m2 ). The primary endpoint, a composite of all-cause mortality or rehospitalization for AHF at 180 days, showed a significant interaction of treatment strategy and sex (p for interaction = 0.03; hazard ratio adjusted for female sex 1.62, 95% confidence interval 1.05-2.50; p = 0.03). The combined endpoint occurred in 53 women (38%) in the intervention group and in 35 (24%) in the usual care group. The implementation of rapid up-titration of renin-angiotensin-aldosterone system (RAAS) inhibitors was less successful in women versus men in the overall cohort and in patients with heart failure with reduced ejection fraction (median discharge % target dose in patients randomized to intervention: 50% in women vs. 75% in men). CONCLUSION: Rapid up-titration of RAAS inhibitors was less successfully implemented in women possibly explaining their higher rate of all-cause mortality and rehospitalization for AHF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, unique identifier NCT00512759.
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Insuficiencia Cardíaca , Femenino , Humanos , Masculino , Presión Sanguínea , Readmisión del Paciente , Sistema Renina-Angiotensina , Vasodilatación , Anciano , Anciano de 80 o más AñosRESUMEN
AIMS: The utility of clinical risk scores regarding the prediction of major adverse cardiac events (MACE) is uncertain. We aimed to directly compare the prognostic performance of five established clinical risk scores as well as an unstructured integrated clinical judgement (ICJ) of the treating emergency department (ED) physician. METHODS AND RESULTS: Thirty-day MACE including all-cause death, life-threatening arrhythmia, cardiogenic shock, acute myocardial infarction (including the index event), and unstable angina requiring urgent coronary revascularization were centrally adjudicated by two independent cardiologists in patients presenting to the ED with acute chest discomfort in an international multicentre study. We compared the prognostic performance of the HEART score, GRACE score, T-MACS, TIMI score, and EDACS, as well as the unstructured ICJ of the treating ED physician (visual analogue scale to estimate the probability of acute coronary syndrome, ranging from 0 to 100). Among 4551 eligible patients, 1110/4551 patients (24.4%) had at least one MACE within 30 days. Prognostic accuracy was high and comparable for the HEART score, GRACE score, T-MACS, and ICJ [area under the receiver operating characteristic curve (AUC) 0.85-0.87] but significantly lower and only moderate for the TIMI score (AUC 0.79, P < 0.001) and EDACS (AUC 0.74, P < 0.001), resulting in sensitivities for the rule-out of 30-day MACE of 93-96, 87 (P < 0.001), and 72% (P < 0.001), respectively. CONCLUSION: The HEART score, GRACE score, T-MACS, and unstructured ICJ of the treating physician, not the TIMI score or EDACS, performed well for the prediction of 30-day MACE and may be considered for routine clinical use. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00470587.
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Síndrome Coronario Agudo , Humanos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/complicaciones , Medición de Riesgo/métodos , Dolor en el Pecho/etiología , Estudios Prospectivos , Factores de Riesgo , Razonamiento Clínico , Servicio de Urgencia en HospitalRESUMEN
AIMS: The presence of accompanying dyspnoea is routinely assessed and common in patients presenting with acute chest pain/discomfort to the emergency department (ED). We aimed to assess the association of accompanying dyspnoea with differential diagnoses, diagnostic work-up, and outcome. METHODS AND RESULTS: We enrolled patients presenting to the ED with chest pain/discomfort. Final diagnoses were adjudicated by independent cardiologists using all information including cardiac imaging. The primary diagnostic endpoint was the final diagnosis. The secondary diagnostic endpoint was the performance of high-sensitivity cardiac troponin (hs-cTn) and the European Society of Cardiology (ESC) 0/1h-algorithms for the diagnosis of myocardial infarction (MI). The prognostic endpoints were cardiovascular and all-cause mortality at two years. Among 6045 patients, 2892/6045 (48%) had accompanying dyspnoea. The prevalence of acute coronary syndrome (ACS) in patients with vs. without dyspnoea was comparable (MI 22.4% vs. 21.9%, P = 0.60, unstable angina 8.7% vs. 7.9%, P = 0.29). In contrast, patients with dyspnoea more often had cardiac, non-coronary disease (15.3% vs. 10.2%, P < 0.001). Diagnostic accuracy of hs-cTnT/I concentrations was not affected by the presence of dyspnoea (area under the curve 0.89-0.91 in both groups), and the safety of the ESC 0/1h-algorithms was maintained with negative predictive values >99.4%. Accompanying dyspnoea was an independent predictor for cardiovascular and all-cause death at two years [hazard ratio 1.813 (95% confidence intervals, 1.453-2.261, P < 0.01)]. CONCLUSION: Accompanying dyspnoea was not associated with a higher prevalence of ACS but with cardiac, non-coronary disease. While the safety of the diagnostic work-up was not affected, accompanying dyspnoea was an independent predictor for cardiovascular and all-cause death. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00470587, number NCT00470587.
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Síndrome Coronario Agudo , Infarto del Miocardio , Humanos , Infarto del Miocardio/diagnóstico , Valor Predictivo de las Pruebas , Pronóstico , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Disnea/diagnóstico , Disnea/epidemiología , Disnea/etiología , Biomarcadores , Troponina TRESUMEN
STUDY OBJECTIVE: The diagnostic performance of T-wave amplitudes for the detection of myocardial infarction is largely unknown. We aimed to address this knowledge gap. METHODS: T-wave amplitudes were automatically measured in 12-lead ECGs of patients presenting with acute chest discomfort to the emergency department within a prospective diagnostic multicenter study. The final diagnosis was centrally adjudicated by 2 independent cardiologists. Patients with left ventricular hypertrophy, complete left bundle branch block, or paced ventricular depolarization were excluded. The performance for lead-specific 95th-percentile thresholds were reported as likelihood ratios (lr), specificity, and sensitivity. RESULTS: Myocardial infarction was the final diagnosis in 445 (18%) of 2457 patients. In most leads, T-wave amplitudes tended to be greater in patients without myocardial infarction than those with myocardial infarction, and T-wave amplitude exceeding the 95th percentile had positive and negative lr close to 1 or with confidence intervals (CIs) crossing 1. The exceptions were leads III, aVR, and V1, which had positive lrs of 3.8 (95% CI, 2.7 to 5.3), 4.3 (95% CI, 3.1 to 6.0) and 2.0 (95% CI, 1.4 to 2.9), respectively. These leads normally have inverted T waves, so T-wave amplitude exceeding the 95th percentile reflects upright rather than increased-amplitude hyperacute T waves. CONCLUSION: Hyperacute T waves, when defined as increased T-wave amplitude exceeding the 95th percentile, did not provide useful information in diagnosing myocardial infarction in this sample.
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Infarto del Miocardio , Humanos , Estudios Prospectivos , Sensibilidad y Especificidad , Infarto del Miocardio/diagnóstico , Arritmias Cardíacas , Electrocardiografía , Diagnóstico PrecozRESUMEN
AIMS: Primary acute heart failure (AHF) is a common cause of hospitalization. AHF may also develop postoperatively (pAHF). The aim of this study was to assess the incidence, phenotypes, determinants and outcomes of pAHF following non-cardiac surgery. METHODS AND RESULTS: A total of 9164 consecutive high-risk patients undergoing 11 262 non-cardiac inpatient surgeries were prospectively included. The incidence, phenotypes, determinants and outcome of pAHF, centrally adjudicated by independent cardiologists, were determined. The incidence of pAHF was 2.5% (95% confidence interval [CI] 2.2-2.8%); 51% of pAHF occurred in patients without known heart failure (de novo pAHF), and 49% in patients with chronic heart failure. Among patients with chronic heart failure, 10% developed pAHF, and among patients without a history of heart failure, 1.5% developed pAHF. Chronic heart failure, diabetes, urgent/emergent surgery, atrial fibrillation, cardiac troponin elevations above the 99th percentile, chronic obstructive pulmonary disease, anaemia, peripheral artery disease, coronary artery disease, and age, were independent predictors of pAHF in the logistic regression model. Patients with pAHF had significantly higher all-cause mortality (44% vs. 11%, p < 0.001) and AHF readmission (15% vs. 2%, p < 0.001) within 1 year than patients without pAHF. After Cox regression analysis, pAHF was an independent predictor of all-cause mortality (adjusted hazard ratio [aHR] 1.7 [95% CI 1.3-2.2]; p < 0.001) and AHF readmission (aHR 2.3 [95% CI 1.5-3.7]; p < 0.001). Findings were confirmed in an external validation cohort using a prospective multicentre cohort of 1250 patients (incidence of pAHF 2.4% [95% CI 1.6-3.3%]). CONCLUSIONS: Postoperative AHF frequently developed following non-cardiac surgery, being de novo in half of cases, and associated with a very high mortality.
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Insuficiencia Cardíaca , Humanos , Estudios Prospectivos , Incidencia , Enfermedad Aguda , Enfermedad Crónica , FenotipoRESUMEN
AIMS: Systemic inflammation may be central in the pathophysiology of acute heart failure (AHF). We aimed to assess the possible role of systemic inflammation in the pathophysiology, phenotyping, and risk stratification of patients with AHF. METHODS AND RESULTS: Using a novel Interleukin-6 immunoassay with unprecedented sensitivity (limit of detection 0.01 ng/L), we quantified systemic inflammation in unselected patients presenting with acute dyspnoea to the emergency department in a multicentre study. One-year mortality was the primary prognostic endpoint. Among 2042 patients, 1026 (50.2%) had an adjudicated diagnosis of AHF, 83.7% of whom had elevated interleukin-6 concentrations (>4.45 ng/L). Interleukin-6 was significantly higher in AHF patients compared to patients with other causes of dyspnoea (11.2 [6.1-26.5] ng/L vs. 9.0 [3.2-32.3] ng/L, p < 0.0005). Elevated interleukin-6 concentrations were independently predicted by increasing N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T, as well as the clinical diagnosis of infection. Among the different AHF phenotypes, interleukin-6 concentrations were highest in patients with cardiogenic shock (25.7 [14.0-164.2] ng/L) and lowest in patients with hypertensive AHF (9.3 [4.8-21.6] ng/L, p = 0.001). Inflammation as quantified by interleukin-6 was a strong and independent predictor of 1-year mortality both in all AHF patients, as well as those without clinically overt infection at presentation (adjusted hazard ratio [95% confidence interval] 1.45 [1.15-1.83] vs. 1.48 [1.09-2.00]). The addition of interleukin-6 significantly improved the discrimination of the BIOSTAT-CHF risk score. CONCLUSION: An unexpectedly high percentage of patients with AHF have subclinical systemic inflammation as quantified by interleukin-6, which seems to contribute to AHF phenotype and to the risk of death.
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Insuficiencia Cardíaca , Humanos , Enfermedad Aguda , Biomarcadores , Disnea , Insuficiencia Cardíaca/diagnóstico , Inflamación , Interleucina-6 , Pronóstico , Estudios Prospectivos , Medición de RiesgoRESUMEN
OBJECTIVE: To investigate the relationship of seasonal flu vaccination with the severity of decompensation and long-term outcomes of patients with heart failure (HF). METHODS: We analyzed 6147 consecutively enrolled patients with decompensated HF who presented to 33 Spanish emergency departments (EDs) during January and February of 2018 and 2019, grouped according to seasonal flu vaccination status. The severity of HF decompensation was assessed by the Multiple Estimation of Risk Based on the Emergency Department Spanish Score in Patients With Acute Heart Failure (MEESSI-AHF)â¯+â¯MEESSI scale, need of hospitalization and in-hospital all-cause mortality. The long-term outcomes analyzed were 90-day postdischarge adverse events and 90-day all-cause death. Associations between vaccination, HF decompensation severity and long-term outcomes were explored by unadjusted and adjusted logistic and Cox regressions by using 14 covariables that could act as potential confounders. RESULTS: Overall median (IQR) age was 84 (IQRâ¯=â¯77-89) years, and 56% were women. Vaccinated patients (nâ¯=â¯1139; 19%) were older, had more comorbidities and had worse baseline status, as assessed by New York Heart Association class and Barthel index, than did unvaccinated patients (nâ¯=â¯5008; 81%). Infection triggering decompensation was more common in vaccinated patients (50% vs 41%; P < 0.001). In vaccinated and unvaccinated patients, high or very-high risk decompensation was seen in 21.9% and 21.1%; hospitalization occurred in 72.5% and 73.7%; in-hospital mortality was 7.4% and 7.0%; 90-day postdischarge adverse events were 57.4% and 53.2%; and the 90-day mortality rate was 15.8% and 16.6%, respectively, with no significant differences between cohorts. After adjusting, vaccinated decompensated patients with HF had decreased odds for hospitalization (ORâ¯=â¯0.823, 95%CIâ¯=â¯0.709-0.955). CONCLUSION: In patients with HF, seasonal flu vaccination is associated with less severe decompensations.
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Insuficiencia Cardíaca , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Masculino , Insuficiencia Cardíaca/epidemiología , Alta del Paciente , Cuidados Posteriores , Hospitalización , VacunaciónRESUMEN
BACKGROUND: We aimed to assess the diagnostic utility of the Dimension EXL LOCI High-Sensitivity Troponin I (hs-cTnI-EXL) assay. METHODS: This multicenter study included patients with chest discomfort presenting to the emergency department. Diagnoses were centrally and independently adjudicated by two cardiologists using all available clinical information. Adjudication was performed twice including serial measurements of high-sensitivity cardiac troponin (hs-cTn) I-Architect (primary analysis) and serial measurements of hs-cTnT-Elecsys (secondary analysis) in addition to the clinically used (hs)-cTn. The primary objective was to assess and compare the discriminatory performance of hs-cTnI-EXL, hs-cTnI-Architect and hs-cTnT-Elecsys for acute myocardial infarction (MI). Furthermore, we derived and validated a hs-cTnI-EXL-specific 0/1h-algorithm. RESULTS: Adjudicated MI was the diagnosis in 204/1454 (14%) patients. The area under the receiver operating characteristics curve for hs-cTnI-EXL was 0.94 (95%CI, 0.93-0.96), and comparable to hs-cTnI-Architect (0.95; 95%CI, 0.93-0.96) and hs-cTnT-Elecsys (0.93; 95%CI, 0.91-0.95). In the derivation cohort (n = 813), optimal criteria for rule-out of MI were <9ng/L at presentation (if chest pain onset >3h) or <9ng/L and 0h-1h-change <5ng/L, and for rule-in ≥160ng/L at presentation or 0h-1h-change ≥100ng/L. In the validation cohort (n = 345), these cut-offs ruled-out 56% of patients (negative predictive value 99.5% (95%CI, 97.1-99.9), sensitivity 97.8% (95%CI, 88.7-99.6)), and ruled-in 9% (positive predictive value 83.3% (95%CI, 66.4-92.7), specificity 98.3% (95%CI, 96.1-99.3)). Secondary analyses using adjudication based on hs-cTnT measurements confirmed the findings. CONCLUSIONS: The overall performance of the hs-cTnI-EXL was comparable to best-validated hs-cTnT/I assays and an assay-specific 0/1h-algorithm safely rules out and accurately rules in acute MI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00470587.
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Infarto del Miocardio , Troponina I , Humanos , Estudios Prospectivos , Biomarcadores , Curva ROC , Infarto del Miocardio/diagnóstico , Troponina TRESUMEN
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).
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AIMS: After rule-out of non-ST elevation myocardial infarction (NSTEMI) with the European Society of Cardiology (ESC) 0/1â h-algorithms, it is unclear which patients require further anatomical or functional cardiac testing. To test the safety and efficacy of the no-objective-testing (NOT)-rules after NSTEMI rule-out by the ESC 0/1â h-algorithms. METHODS AND RESULTS: International, prospective, diagnostic multicentre study enrolling adult patients presenting with chest pain to the emergency department. Central adjudication of final diagnosis by two independent cardiologists using information including cardiac imaging. Primary endpoints were the safety and efficacy of the NOT-rules for the rule-out of major adverse cardiovascular events (MACE). Secondary endpoints included 365-day and 2-year MACE. Among 4804 and 4569 patients with available 0/1â h high-sensitivity cardiac troponin (hs-cTn)T-Elecsys or hs-cTnI-Architect concentrations, 2783 (58%) and 2252 (49%) were eligible for application of the NOT-rules after rule-out of NSTEMI by the ESC hs-cTnT/I-0/1h-algorithm. The first rule identified 26% of patients with a sensitivity of 100% (95%CI 98.3-100%) and a negative predictive value (NPV) of 100% (95% CI, n.c.). The second and third rules both identified 31% of patients with a sensitivity of 99.5% (95% CI 97.4-99.9%) and a NPV of 99.9% (95% CI 99.2-99.9%). Similar findings emerged for hs-cTnI. High safety was confirmed for rule-out of 365-day and 2-year MACE and proven to be superior to the HEART Score. CONCLUSION: All three NOT-rules performed very well for rule-out of MACE. The third NOT-rule best balanced feasibility, safety, and efficacy by identifying nearly one out of three patients as low-risk and may not require further cardiac testing. https://clinicaltrials.gov/ct2/show/NCT00470587.
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Cardiología , Infarto del Miocardio , Infarto del Miocardio sin Elevación del ST , Adulto , Humanos , Infarto del Miocardio sin Elevación del ST/diagnóstico , Estudios Prospectivos , Infarto del Miocardio/diagnóstico , Troponina I , Algoritmos , Biomarcadores , Troponina TRESUMEN
AIMS: Obese patients have lower natriuretic peptide concentrations. We hypothesized that adjusting the concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for obesity could further increase its clinical utility in the early diagnosis of acute heart failure (AHF). METHODS AND RESULTS: This hypothesis was tested in a prospective diagnostic study enrolling unselected patients presenting to the emergency department with acute dyspnoea. Two independent cardiologists/internists centrally adjudicated the final diagnosis using all individual patient information including cardiac imaging. NT-proBNP plasma concentrations were applied: first, using currently recommended cut-offs; second, using cut-offs lowered by 33% with body mass index (BMI) of 30-34.9 kg/m2 and by 50% with BMI ≥ 35 kg/m2 . Among 2038 patients, 509 (25%) were obese, of which 271 (53%) had AHF. The diagnostic accuracy of NT-proBNP as quantified by the area under the receiver-operating characteristic curve was lower in obese versus non-obese patients (0.890 vs. 0.938). For rapid AHF rule-out in obese patients, the currently recommended cut-off of 300 pg/ml achieved a sensitivity of 96.7% (95% confidence interval [CI] 93.8-98.2%), ruling out 29% of patients and missing 9 AHF patients. For rapid AHF rule-in, the age-dependent cut-off concentrations (age <50 years: 450 pg/ml; age 50-75 years: 900 pg/ml; age >75 years: 1800 pg/ml) achieved a specificity of 84.9% (95% CI 79.8-88.9%). Proportionally lowering the currently recommended cut-offs by BMI increased sensitivity to 98.2% (95% CI 95.8-99.2%), missing 5 AHF patients; reduced the proportion of AHF patients remaining in the 'gray zone' (48% vs. 26%; p = 0.002), achieving a specificity of 76.5% (95% CI 70.7-81.4%). CONCLUSIONS: Adjusting NT-proBNP concentrations for obesity seems to further increase its clinical utility in the early diagnosis of AHF.
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Insuficiencia Cardíaca , Péptido Natriurético Encefálico , Enfermedad Aguda , Anciano , Biomarcadores , Insuficiencia Cardíaca/diagnóstico , Humanos , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/diagnóstico , Fragmentos de Péptidos , Estudios ProspectivosRESUMEN
BACKGROUND: Current American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) and European Society of Cardiology (ESC) guidelines recommend different strategies to avoid low-yield admissions in patients with syncope. OBJECTIVE: The purpose of this study was to directly compare the safety and efficacy of applying admission criteria of both guidelines to patients presenting with syncope to the emergency department in 2 multicenter studies. METHODS: The international BASEL IX (BAsel Syncope EvaLuation) study (median age 71 years) and the U.S. SRS (Improving Syncope Risk Stratification in Older Adults) study (median age 72 years) were investigated. Primary endpoints were sensitivity/specificity for the adjudicated diagnosis of cardiac syncope (BASEL IX only) and 30-day major adverse cardiovascular events (30d-MACE). RESULTS: Among 2560 patients in the BASEL IX and 2085 in SRS studies, ACC/AHA/HRS and ESC criteria recommended admission for a comparable number of patients in BASEL IX (27% vs 28%), but ACC/AHA/HRS criteria less often in SRS (19% vs 32%; P <.01). Recommendations were discordant in â¼25% of patients. In BASEL IX, sensitivity for cardiac syncope and 30d-MACE among patients without admission criteria was comparable for ACC/AHA/HRS and ESC criteria (64% vs 65%, P = .86; and 67% vs 71%, P = .15, respectively). In SRS, sensitivity for 30d-MACE was lower with ACC/AHA/HRS (54%) vs ESC criteria (88%; P <.001). Similarly, specificity for cardiac syncope and 30d-MACE in BASEL IX was comparable for both guidelines, but in SRS the ACC/AHA/HRS guidelines showed a higher specificity for 30d-MACE than the ESC guidelines. CONCLUSION: ACC/AHA/HRS and ESC guidelines showed disagreement regarding admission for 1 in 4 patients and had only modest sensitivity, all indicating possible opportunities for improvements.
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American Heart Association , Cardiología , Anciano , Hospitalización , Hospitales , Humanos , Síncope/diagnóstico , Síncope/terapia , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVES: To evaluate the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for acute heart failure and to develop and validate a decision support tool that combines NT-proBNP concentrations with clinical characteristics. DESIGN: Individual patient level data meta-analysis and modelling study. SETTING: Fourteen studies from 13 countries, including randomised controlled trials and prospective observational studies. PARTICIPANTS: Individual patient level data for 10 369 patients with suspected acute heart failure were pooled for the meta-analysis to evaluate NT-proBNP thresholds. A decision support tool (Collaboration for the Diagnosis and Evaluation of Heart Failure (CoDE-HF)) that combines NT-proBNP with clinical variables to report the probability of acute heart failure for an individual patient was developed and validated. MAIN OUTCOME MEASURE: Adjudicated diagnosis of acute heart failure. RESULTS: Overall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure (73.3% (2286/3119) and 29.0% (1802/6208) in those with and without previous heart failure, respectively). The negative predictive value of the guideline recommended rule-out threshold of 300 pg/mL was 94.6% (95% confidence interval 91.9% to 96.4%); despite use of age specific rule-in thresholds, the positive predictive value varied at 61.0% (55.3% to 66.4%), 73.5% (62.3% to 82.3%), and 80.2% (70.9% to 87.1%), in patients aged <50 years, 50-75 years, and >75 years, respectively. Performance varied in most subgroups, particularly patients with obesity, renal impairment, or previous heart failure. CoDE-HF was well calibrated, with excellent discrimination in patients with and without previous heart failure (area under the receiver operator curve 0.846 (0.830 to 0.862) and 0.925 (0.919 to 0.932) and Brier scores of 0.130 and 0.099, respectively). In patients without previous heart failure, the diagnostic performance was consistent across all subgroups, with 40.3% (2502/6208) identified at low probability (negative predictive value of 98.6%, 97.8% to 99.1%) and 28.0% (1737/6208) at high probability (positive predictive value of 75.0%, 65.7% to 82.5%) of having acute heart failure. CONCLUSIONS: In an international, collaborative evaluation of the diagnostic performance of NT-proBNP, guideline recommended thresholds to diagnose acute heart failure varied substantially in important patient subgroups. The CoDE-HF decision support tool incorporating NT-proBNP as a continuous measure and other clinical variables provides a more consistent, accurate, and individualised approach. STUDY REGISTRATION: PROSPERO CRD42019159407.
Asunto(s)
Insuficiencia Cardíaca , Péptido Natriurético Encefálico , Biomarcadores , Diagnóstico Diferencial , Insuficiencia Cardíaca/diagnóstico , Humanos , Estudios Observacionales como Asunto , Fragmentos de Péptidos , Valor Predictivo de las Pruebas , Estudios ProspectivosRESUMEN
BACKGROUND: Current guidelines recommend interpreting concentrations of NPs (natriuretic peptides) irrespective of the time of presentation to the emergency department. We hypothesized that diurnal variations in NP concentration may affect their diagnostic accuracy for acute heart failure. METHODS: In a secondary analysis of a multicenter diagnostic study enrolling patients presenting with acute dyspnea to the emergency department and using central adjudication of the final diagnosis by 2 independent cardiologists, the diagnostic accuracy for acute heart failure of BNP (B-type NP), NT-proBNP (N-terminal pro-B-type NP), and MR-proANP (midregional pro-atrial NP) was compared among 1577 daytime presenters versus 908 evening/nighttime presenters. In a validation study, the presence of a diurnal rhythm in BNP and NT-proBNP concentrations was examined by hourly measurements in 44 stable individuals. RESULTS: Among patients adjudicated to have acute heart failure, BNP, NT-proBNP, and MR-proANP concentrations were comparable among daytime versus evening/nighttime presenters (all P=nonsignificant). Contrastingly, among patients adjudicated to have other causes of dyspnea, evening/nighttime presenters had lower BNP (median, 44 [18-110] versus 74 [27-168] ng/L; P<0.01) and NT-proBNP (median, 212 [72-581] versus 297 [102-902] ng/L; P<0.01) concentrations versus daytime presenters. This resulted in higher diagnostic accuracy as quantified by the area under the curve of BNP and NT-proBNP among evening/nighttime presenters (0.97 [95% CI, 0.95-0.98] and 0.95 [95% CI, 0.93-0.96] versus 0.94 [95% CI, 0.92-0.95] and 0.91 [95% CI, 0.90-0.93]) among daytime presenters (both P<0.01). These differences were not observed for MR-proANP. Diurnal variation of BNP and NT-proBNP with lower evening/nighttime concentration was confirmed in 44 stable individuals (P<0.01). CONCLUSIONS: BNP and NT-proBNP, but not MR-proANP, exhibit a diurnal rhythm that results in even higher diagnostic accuracy among evening/nighttime presenters versus daytime presenters. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT01831115, NCT02091427, and NCT02210897.