Àngel Llàcer

Usefulness of the Neutrophil to Lymphocyte Ratio in Predicting Long-Term Mortality in ST Segment Elevation Myocardial Infarction

Neutrophil to lymphocyte ratio (N/L) has been associated with poor outcomes in patients who underwent cardiac angiography. Nevertheless, its role for risk stratification in acute coronary syndromes, specifically in patients with ST-segment elevation myocardial infarction (STEMI), has not been elucidated. We sought to determine the association of N/L maximum value (N/L max) with mortality in the setting of STEMI and to compare its predictive ability with total white blood cell maximum count (WBC max). We analyzed 515 consecutive patients admitted with STEMI to a single university center. White blood cells (WBC) and differential count were measured at admission and daily for the first 96 hours afterward. Patients with cancer, inflammatory diseases, or premature death were excluded, and 470 patients were included in the final analysis. The association between N/L max and WBC max with mortality was assessed by Cox regression analysis. During follow-up, we registered 106 deaths (22.6%). A positive trend between mortality and N/L max quintiles was observed; 6.4%, 12.4%, 11.7%, 34%, and 47.9% of deaths occurred from quintiles 1 to 5 (p <0.001), respectively. In a multivariable setting, after adjusting for standard risk factors, patients in the fourth (Q4 vs Q1) and fifth quintile (Q5 vs Q1) showed the highest mortality risk (hazard ratio 2.58, 95% confidence interal 1.06 to 6.32, p = 0.038 and hazard ratio 4.20, 95% confidence interal 1.73 to 10.21, p = 0.001, respectively). When WBC max and cells subtypes were entered together, N/L max remained as the only WBC parameter; furthermore, the model with N/L max showed the most discriminative ability. In conclusion, N/L max is a useful marker to predict subsequent mortality in patients admitted for STEMI, with a superior discriminative ability than total WBC max.

Prognostic value of a comprehensive cardiac magnetic resonance assessment soon after a first ST-segment elevation myocardial infarction.

OBJECTIVES To evaluate the prognostic value of a comprehensive cardiac magnetic resonance (CMR) assessment soon after a first ST-segment elevation myocardial infarction (STEMI). BACKGROUND CMR allows for a simultaneous assessment of wall motion abnormalities (WMA), WMA with low-dose dobutamine (WMA-dobutamine), microvascular obstruction, and transmural necrosis. This approach has been proven to be useful to predict late systolic recovery soon after STEMI. Its prognostic value and the relative prognostic weight of these indexes are not well-defined. METHODS We studied 214 consecutive patients with a first STEMI treated with thrombolytic therapy or primary angioplasty discharged from hospital. In the first week (7 +/- 1 day after infarction), with CMR we determined the extent (number of segments) of WMA, WMA-dobutamine, microvascular obstruction, and transmural necrosis. RESULTS During a median follow-up of 553 days, 21 major adverse cardiac events (MACE) including 4 cardiac deaths, 6 nonfatal myocardial infarctions, and 11 readmissions for heart failure were documented. The MACE was associated with a larger extent of WMA (8 +/- 4 segments vs. 5 +/- 3 segments, p < 0.001), WMA-dobutamine (6 +/- 4 segments vs. 4 +/- 3 segments, p = 0.004), microvascular obstruction (3 +/- 3 segments vs. 1 +/- 2 segments p <0.001), and transmural necrosis (7 +/- 3 segments vs. 3 +/- 3 segments, p < 0.001). In a complete multivariate analysis that included baseline characteristics, electrocardiogram, biomarkers, angiography, ejection fraction, left ventricular volumes, and all CMR indexes, WMA/segment (hazard ratio: 1.29 [95% confidence interval: 1.11 to 1.49], p = 0.001) and the extent of transmural necrosis/segment (hazard ratio: 1.30 [95% confidence interval: 1.12 to 1.51], p < 0.001) were the only independent prognostic variables. CONCLUSIONS A comprehensive CMR assessment is useful for stratifying risk soon after STEMI, but only the extent of systolic dysfunction and of transmural necrosis provide independent prognostic information.

Prevalence and Prognostic Influence of Peripheral Arterial Disease in Patients ≥40 Years Old Admitted into Hospital Following an Acute Coronary Event

OBJECTIVE A significant proportion of patients with ischemic heart disease have associated peripheral arterial disease (PAD), but many are asymptomatic and this condition remains underdiagnosed. We aimed to study the prevalence of PAD in patients with an acute coronary syndrome (ACS) and to evaluate its influence in hospital clinical outcomes. METHODS The PAMISCA register is a prospective, multicenter study involving patients >or=40 years old with ACS admitted to selected Spanish hospitals. All patients had their ankle-brachial index (ABI) measured between days 3 and 7 after the ischemic event. RESULTS 1410 ACS patients (71.4% male) were included. PAD determined by ABI was documented in 561 patients (39.8%). Factors independently related to PAD were age (OR: 1.04; 95% CI: 1.03-1.06; p<0.001), smoking (OR: 1.88; 95% CI: 1.41-2.49; p<0.0001), diabetes (OR: 1.30; 95% CI: 1.02-1.65; p<0.05), previous cardiac disease (OR: 1.54; 95% CI: 1.22-1.95; p<0.001) and previous cerebrovascular disease (OR: 1.90; 95% CI: 1.28-2.80; p<0.001). Following the ACS, an ABI<or=0.90 was associated with increased cardiovascular mortality (OR: 5.45; 95% CI: 1.16-25.59; p<0.05) and a higher risk of cardiovascular complications. CONCLUSION The prevalence of PAD in patients >or=40 years presenting with ACS is high and it is associated with increased cardiovascular risk.

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.

Selective use of diagnostic tests inpatients with syncope of unknown cause

OBJECTIVE We sought to prospectively assess the diagnostic yielding of a protocol in which electrophysiologic studies (EPS), tilt-table tests (TTTs), and loop recorder implantation are selectively used. BACKGROUND The optimal strategy in the diagnosis of patients with syncope of unknown cause has not been defined. METHODS A total of 184 consecutive patients with syncope of unknown cause were classified into two groups. Group A consisted of 72 patients fulfilling any of the following criteria: 1) presence of structural heart disease or family history of sudden death; 2) abnormal electrocardiogram; 3) significant non-symptomatic arrhythmia on Holter monitoring; and 4) paroxysmal palpitations immediately before or after syncope. These patients initially underwent an EPS and, if this study was negative, TTT. In the remaining 112 patients (group B), TTT was performed. RESULTS The EPS was positive in 32 patients (44%) in group A. The TTT was positive in 80 patients (71%) in group B. An additional patient had carotid sinus hypersensitivity. In patients of group A with a negative EPS, the TTT was positive in 23 (57%). A loop recorder was implanted in 15 patients from group A with negative conventional testing, and diagnostic activation was obtained in seven patients. Overall, a positive diagnosis was achieved in 143 patients (78%). CONCLUSIONS In patients with syncope of unknown cause, selective use of EPS or TTT leads to a positive diagnosis in >70% of the cases. An implantable loop recorder can be useful in non-diagnosed cases.

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.

Continuous ambulatory peritoneal dialysis as a therapeutic alternative in patients with advanced congestive heart failure

Continuous ambulatory peritoneal dialysis (CAPD) has been proposed as an additional therapeutic resource for patients with advanced congestive heart failure (CHF). The objective of this study was to determine the therapeutic role of CAPD, in terms of surrogate endpoints, in the management of patients with advanced CHF and renal dysfunction.

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.

Uncontrolled immune response in acute myocardial infarction: Unraveling the thread

Recently, the theory that hyperinflammation is the bodys primary response to potent stimulus has been challenged. Indeed, a deregulation of the immune system could be the cause of multiple organ failure. So far, clinicians have focused on the last steps of the inflammatory cascade. However, little attention has been paid to lymphocytes, which play an important role as strategists of the inflammatory response. Experimental evidence suggests a crucial role of T lymphocytes in the pathophysiology of atherosclerosis and acute myocardial infarction (AMI). In summary, from the bottom of an imaginary inverted pyramid, a few regulatory T-cells control the upper parts represented by the wide spectrum of the inflammatory cascade. In AMI, a loss of regulation of the inflammatory system occurs in patients with a decreased activity of regulatory T-cells. As a consequence, aggressive T-cells boost and anti-inflammatory T-cells drop. A pleiotropic proinflammatory imbalance with damaging effects in terms of left ventricular performance and patient outcome is the result of this uncontrolled immune response. It is needed to unravel the thread of the inflammatory cells to better understand the pathophysiology as well as to open innovative therapeutic options in AMI.