María J. Bosch

Improvement in risk stratification with the combination of the tumour marker antigen carbohydrate 125 and brain natriuretic peptide in patients with acute heart failure

AIM Elevated brain natriuretic peptide (BNP) and tumour marker antigen carbohydrate 125 (CA125) levels have shown to be associated with higher risk for adverse outcomes in patients with acute heart failure (AHF). Nevertheless, no attempt has been made to explore the utility of combining these two biomarkers. We sought to assess whether CA125 adds prognostic value to BNP in predicting 6-month all-cause mortality in patients with AHF. METHODS AND RESULTS We analysed 1111 consecutive patients admitted for AHF. Antigen carbohydrate 125 (U/mL) and BNP (pg/mL) were measured at a median of 72 +/- 12 h after instauration of treatment. Antigen carbohydrate 125 and BNP were dichotomized based on proposed prognostic cutpoints, and a variable with four categories was formed (BNP-CA125): C1 = BNP < 350 and CA125 < 60 (n = 394); C2 = BNP > or = 350 and CA125 < 60 (n = 165); C3 = BNP < 350 and CA125 > or = 60 (n = 331); and C4 = BNP > or = 350 and CA125 > or = 60 (n = 221). The independent association between BNP-CA125 and mortality was assessed with the Cox regression analysis, and their added predictive ability tested by the integrated discrimination improvement (IDI) index. At 6 months, 181 deaths (16.3%) were identified. The cumulative rate of mortality was lower for patients in C1 (7.8%), intermediate for C2 and C3 (17.8% and 16.9%, respectively), and higher for C4 (37.2%), and P-value for trend <0.001. After adjusting for established risk factors, the highest risk was observed when both biomarkers were elevated (C4 vs. C1: HR = 4.05, 95% CI = 2.54-6.45; P < 0.001) and intermediate when only one of them was elevated: (C2 vs. C1: HR = 1.71, 95% CI = 1.00-2.93; P = 0.050) and (C3 vs. C1: HR = 2.10, 95% CI = 1.30-3.39; P = 0.002). Moreover, when CA125 was added to the clinical model + BNP, a 10.4% (P < 0.0001) improvement in the IDI (on the relative scale) was found. CONCLUSION In patients admitted with AHF, CA125 added prognostic value beyond the information provided by BNP, and thus, their combination enables better 6-month risk stratification.

Risk stratification of patients with acute chest pain and normal troponin concentrations

Objective: To investigate the outcome of patients with acute chest pain and normal troponin concentrations. Design: Prospective cohort design. Setting: Single centre study in a teaching hospital in Spain. Patients: 609 consecutive patients with chest pain evaluated in the emergency department by clinical history (risk factors and a chest pain score according to pain characteristics), ECG, and early (< 24 hours) exercise testing for low risk patients with physical capacity (n  =  283, 46%). All had normal troponin concentrations after serial determination. Main outcome measures: Myocardial infarction or cardiac death during six months of follow up. Results: 29 events were detected (4.8%). No patient with a negative early exercise test (n  =  161) had events versus the 6.9% event rate in the remaining patients (p  =  0.0001). Four independent predictors were found: chest pain score ⩾ 11 points (odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1 to 5.5, p  =  0.04), diabetes mellitus (OR 2.3, 95% CI 1.1 to 4.7, p  =  0.03), previous coronary surgery (OR 3.1, 95% CI 1.3 to 7.6, p  =  0.01), and ST segment depression (OR 2.8, 95% CI 1.3 to 6.3, p  =  0.003). A risk score proved useful for patient stratification according to the presence of 0–1 (2.7% event rate), 2 (10.2%, p  =  0.008), and 3–4 predictors (29.2%, p  =  0.0001). Conclusions: A negative troponin result does not assure a good prognosis for patients coming to the emergency room with chest pain. Early exercise testing and clinical data should be carefully evaluated for risk stratification.

Cardiovascular magnetic resonance-derived intramyocardial hemorrhage after STEMI: Influence on long-term prognosis, adverse left ventricular remodeling and relationship with microvascular obstruction

BACKGROUND T2 weighted cardiovascular magnetic resonance (CMR) can detect intramyocardial hemorrhage (IMH) after ST-elevation myocardial infarction (STEMI). The long-term prognostic value of IMH beyond a comprehensive CMR assessment with late enhancement (LE) imaging including microvascular obstruction (MVO) is unclear. The value of CMR-derived IMH for predicting major adverse cardiac events (MACE) and adverse cardiac remodeling after STEMI and its relationship with MVO was analyzed. METHODS CMR including LE and T2 sequences was performed in 304 patients 1 week after STEMI. Adverse remodeling was defined as dilated left ventricular end-systolic volume indexes (dLVESV) at 6 months CMR. RESULTS During a median follow-up of 140 weeks, 47 MACE (10 cardiac deaths, 16 myocardial infarctions, 21 heart failure episodes) occurred. Predictors of MACE were ejection fraction (HR .95 95% CI [.93-.97], p=.001, per %) and IMH (HR 1.17 95% CI [1.03-1.33], p=.01, per segment). The extent of MVO and IMH significantly correlated (r=.951, p<.0001). dLVESV was present in 40% of patients. CMR predictors of dLVESV were: LVESV (OR 1.11 95% CI [1.07-1.15], p<.0001, per ml/m(2)), infarct size (OR 1.05 95% CI [1.01-1.09], p=.02, per %) and IMH (OR 1.54 95% CI [1.15-2.07], p=.004, per segment). Addition of T2 information did not improve the LE and cine CMR-model for predicting MACE (.744 95% CI [.659-.829] vs. .734 95% CI [.650-.818], p=.6) or dLVESV (.914 95% CI [.875-.952] vs. .913 95% CI [.875-.952], p=.9). CONCLUSIONS IMH after STEMI predicts MACE and adverse remodeling. Nevertheless, with a strong interrelation with MVO, the addition of T2 imaging does not improve the predictive value of LE-CMR.

Carbohydrate Antigen 125: An Emerging Prognostic Risk Factor in Acute Heart Failure?

Objective: To assess whether circulating levels of carbohydrate antigen 125 (CA125) predict subsequent 6-month all-cause mortality in patients after the index hospitalisation for acute heart failure (HF). Design and setting: Prospective cohort study at a single teaching centre in Spain. Methods: 529 consecutive patients with acute HF admitted in a single university centre were analysed. In addition to the traditional clinical information, CA125 (U/ml) was measured during the early course of hospitalisation. The independent association between baseline CA125 and mortality was assessed with Cox regression analysis. The follow-up was limited to 6 months. Results: 349 (66%) patients showed serum levels of CA125 >35 U/ml (established cut-off point value). At a 6-month follow-up, 89 (16.8%) deaths were identified. A positive trend between mortality and CA125 quartiles was observed; 3.8%, 15.2%, 22% and 26.5% of deaths occurred from quartile 1 to 4 of CA125 (p<0.001). Likewise, a monotonic, ascending trend in the risk ratios was estimated from the multivariable Cox model. Compared with the first quartile of CA125, the HRs (95% CI) for the second, third and fourth quartiles were 3.25 (1.20 to 8.79), 4.91 (1.88 to 12.85) and 8.41 (3.24 to 21.79), respectively. Conclusions: Serum levels of CA125 obtained in patients admitted with a diagnosis of acute HF was shown to be an independent predictor of mortality up to the 6-month follow-up.

Contractile Reserve and Extent of Transmural Necrosis in the Setting of Myocardial Stunning: Comparison at Cardiac MR Imaging

PURPOSE To perform a comparison of cardiac magnetic resonance (MR) imaging-derived ejection fraction (EF) during low-dose dobutamine infusion (EF(D)) with the extent of segments with transmural necrosis in more than 50% of their wall thickness (ETN) for the prediction of major adverse cardiac events (MACEs) and late systolic recovery soon after a first ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS Institutional ethics committee approval and written informed consent were obtained. One hundred nineteen consecutive patients with a first STEMI, a depressed left ventricular EF, and an open infarct-related artery underwent MR imaging at 1 week after infarction. EF(D) and ETN (by using a 17-segment model) were determined, and the prediction of MACEs and systolic recovery at follow-up was assessed by using area under the receiver operating characteristic curve (AUC) and multivariable regression analysis. RESULTS During follow-up (median, 613 days; range, 312-1243 days), 18 MACEs (five cardiac deaths, six myocardial infarctions, seven readmissions for heart failure) occurred. MACEs were associated with a lower EF(D) (43% +/- 12 [standard deviation] vs 49% +/- 10, P = .02) and a larger ETN (seven segments +/- three vs four segments +/- three, P < .001). Patients with systolic recovery (increase in EF of >5% at follow-up compared with baseline EF, n = 44) displayed a higher EF(D) (51% +/- 10 vs 47% +/- 9, P = .04) and a smaller ETN (three segments +/- two vs five segments +/- three, P = .002) at 1 week. ETN and EF(D) both related to MACEs (AUC: 0.78 vs 0.67, respectively, P = .1) and systolic recovery (AUC: 0.68 vs 0.62, respectively, P = .3). According to multivariable analysis, ETN was the only MR variable associated with time to MACEs (hazard ratio, 1.38; 95% confidence interval: 1.19, 1.60; P < .001) and systolic recovery (odds ratio, 0.76; 95% confidence interval: 0.64, 0.92; P = .004) independent of baseline characteristics. CONCLUSION ETN is as useful as EF(D) for the prediction of MACEs and systolic recovery soon after STEMI.

Prognostic implications of dipyridamole cardiac MR imaging: a prospective multicenter registry.

PURPOSE To evaluate dipyridamole cardiac magnetic resonance (MR) imaging in the prediction of major events (MEs) in patients with ischemic chest pain in a large multicenter registry. MATERIALS AND METHODS Institutional ethics committee approval and written informed consent were obtained. A total of 1722 patients who were undergoing cardiac MR imaging for chest pain were included. Wall motion abnormalities (WMAs) at rest, hyperemia perfusion defect (PD), late gadolinium enhancement (LGE), and inducible WMA were analyzed (abnormal if more than one abnormal segment was seen) with the 17-segment model. A cardiac MR categorization was created: category 1, no PD, LGE, or inducible WMA; category 2, PD without LGE and inducible WMA; category 3, LGE without inducible WMA; and category 4, inducible WMA. The association with ME was analyzed by using Cox proportional hazard regression multivariate models. RESULTS During a median follow-up period of 308 days, 61 MEs (4%) occurred (36 cardiac deaths, 25 nonfatal myocardial infarctions). MEs were associated with a greater extent of WMA, PD, LGE, and inducible WMA (P ≤ .001 for all analyses). In multivariable analyses, PD (P = .002) and inducible WMA (P = .0001) were the only cardiac MR predictors. ME rate in categories 1, 2, 3, and 4 was 2% (14 of 901 patients), 3% (six of 219 patients), 4% (15 of 409 patients), and 14% (26 of 193 patients), respectively (category 4 vs category 1, adjusted P < .001). Cardiac MR-directed revascularization was performed in 242 patients (14%) and reduced the risk of ME in only category 4 (7% [six of 92 patients] vs 26% [26 of 101 patients], P = .0004). CONCLUSION Dipyridamole cardiac MR imaging can be used to predict MEs in patients with ischemic chest pain. Patients with inducible WMA are at the highest risk for MEs and benefit the most from revascularization.

Long-term Prognostic Value of a Comprehensive Assessment of Cardiac Magnetic Resonance Indexes After an ST-segment Elevation Myocardial Infarction

INTRODUCTION AND OBJECTIVES A variety of cardiac magnetic resonance indexes predict mid-term prognosis in ST-segment elevation myocardial infarction patients. The extent of transmural necrosis permits simple and accurate prediction of systolic recovery. However, its long-term prognostic value beyond a comprehensive clinical and cardiac magnetic resonance evaluation is unknown. We hypothesized that a simple semiquantitative assessment of the extent of transmural necrosis is the best resonance index to predict long-term outcome soon after a first ST-segment elevation myocardial infarction. METHODS One week after a first ST-segment elevation myocardial infarction we carried out a comprehensive quantification of several resonance parameters in 206 consecutive patients. A semiquantitative assessment (altered number of segments in the 17-segment model) of edema, baseline and post-dobutamine wall motion abnormalities, first pass perfusion, microvascular obstruction, and the extent of transmural necrosis was also performed. RESULTS During follow-up (median 51 months), 29 patients suffered a major adverse cardiac event (8 cardiac deaths, 11 nonfatal myocardial infarctions, and 10 readmissions for heart failure). Major cardiac events were associated with more severely altered quantitative and semiquantitative resonance indexes. After a comprehensive multivariate adjustment, the extent of transmural necrosis was the only resonance index independently related to the major cardiac event rate (hazard ratio=1.34 [1.19-1.51] per each additional segment displaying>50% transmural necrosis, P<.001). CONCLUSIONS A simple and non-time consuming semiquantitative analysis of the extent of transmural necrosis is the most powerful cardiac magnetic resonance index to predict long-term outcome soon after a first ST-segment elevation myocardial infarction.

Estrategia invasiva en el síndrome coronario agudo sin elevación del segmento ST. De los grandes estudios al mundo real

Rev Esp Cardiol 2004;57(12):1143-5

Valor pronóstico del recuento leucocitario en el infarto agudo de miocardio: mortalidad a largo plazo

Introduccion y objetivos. Publicaciones recientes respaldan el papel pronostico del recuento leucocitario (RL) en pacientes con infarto agudo de miocardio (IAM). El objetivo de este trabajo fue determinar el valor predictivo atribuible al RL, con independencia de otras variables de contrastado valor pronostico, para predecir mortalidad a largo plazo en pacientes con IAM sin elevacion del segmento ST (IAMSEST) y con elevacion del segmento ST (IAMEST). Pacientes y metodo. Analizamos a 1.118 pacientes admitidos de forma consecutiva con el diagnostico de IAM (IAMSEST = 569; IAMEST = 549). El RL se obtuvo en la primera determinacion analitica. Se utilizaron modelos de regresion de Cox para determinar el grado de asociacion entre el RL y la mortalidad total para ambos tipos de IAM. La mediana de seguimiento fue de 10 ± 2 meses. El RL se incluyo en ambos modelos categorizado en los siguientes puntos de corte (x 10³ celulas/ml): < 10 (RL1); 10-14,9 (RL2) y = 15 (RL3). Resultados. Durante el seguimiento se registraron 105 muertes (18,5%) en pacientes con IAMSEST y 109 (19,9%) con IAMEST. Las hazard ratio ajustadas para las categorias RL2 y RL3 frente a RL1 en el grupo con IAMSEST fueron: 1,61 (1,03-2,51; p = 0,036) y 2,07 (1,08-3,94; p = 0,027), y en el IAMEST: 2,22 (1,35-3,63; p = 0,002) y 2,07 (1,13-3,76; p = 0,017), respectivamente. Conclusiones. El RL determinado en las primeras horas de un IAM demostro ser un predictor independiente de otras variables de contrastado valor pronostico para predecir la mortalidad total a largo plazo en el IAMSEST y el IAMEST.

Prognostic Value of White Blood Cell Count in Acute Myocardial Infarction: Long-Term Mortality

INTRODUCTION AND OBJECTIVES Although traditionally an elevated white blood cell count (WBC), an indicator of systemic inflammation, has been accepted as part of the healing response following acute myocardial infarction (AMI), it has frequently been shown to be a predictor of adverse cardiovascular events. The present study was designed to assess the association between WBC and long-term mortality in AMI patients either with ST-segment elevation (STEMI) or without ST-segment elevation (non-STEMI). Patients and method. The study included 1118 consecutive patients who were admitted with the diagnosis of AMI: 569 non-STEMI and 549 STEMI. The WBC was measured in the 24 hours following admission. Patients were divided into 3 groups: WBC1 (count, <10 x 103 cells/mL), WBC2 (count, 10-14.9 x 10(3) cells/mL), and WBC3 (count, > or =15x10(3) cells/mL). All-cause mortality was recorded during a median follow-up period of 10+/-2 months. The relationship between WBC and mortality was assessed by Cox regression analysis for both types of AMI. RESULTS Long-term mortality during follow-up was 18.5% in non-STEMI patients and 19.9% in STEMI patients. In non-STEMI patients, the adjusted hazard ratios for those in the WBC3 and WBC2 groups compared with those in the WBC1 group were 2.07 (1.08-3.94; P=.027) and 1.61 (1.03-2.51; P=.036), respectively. The corresponding figures in STEMI patients were 2.07 (1.13-3.76; P=.017) and 2.22 (1.35-3.63; P=.002), respectively. CONCLUSIONS WBC on admission was an independent predictor of long-term mortality in both non-STEMI and STEMI patients.