Francisco J. Chorro

Prevalence of Atrial Fibrillation in Spain. OFRECE Study Results

INTRODUCTION AND OBJECTIVES Atrial fibrillation is associated with substantial morbidity and mortality and both its incidence and prevalence are high. Nevertheless, comprehensive data on this condition in Spain are lacking. The aim of this study was to estimate the prevalence of atrial fibrillation in Spain. METHODS A cross-sectional study was conducted in the general Spanish population older than 40 years. Two-stage random sampling was used, in which first-stage units were primary care physicians randomly selected in every Spanish province and second-stage units were 20 randomly selected persons drawn from each participating physicians assigned population. The reported prevalence was standardized for the age and sex distribution of the Spanish population. The electrocardiogram recordings were read centrally. RESULTS Overall, 8343 individuals were evaluated. The mean age was 59.2 years (95% confidence interval, 58.6-59.8 years), and 52.4% of the participants were female. The overall age-adjusted prevalence of atrial fibrillation was 4.4% (95% confidence interval, 3.8-5.1). Prevalence was similar in both sexes, men 4.4% (3.6-5.2) and women 4.5% (3.6-5.3), rising with increasing age older than 60 years. In patients older than 80 years, the prevalence was 17.7% (14.1-21.3). In 10% of patients an unknown atrial fibrillation was diagnosed. CONCLUSIONS The prevalence of atrial fibrillation in the general Spanish population older than 40 years is high, at 4.4%. The prevalence is similar in both sexes and rises steeply above 60 years of age. It is estimated that there are over 1 million patients with atrial fibrillation in the Spanish population, of whom over 90,000 are undiagnosed.

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.

An open access database for the evaluation of heart sound algorithms

In the past few decades, analysis of heart sound signals (i.e. the phonocardiogram or PCG), especially for automated heart sound segmentation and classification, has been widely studied and has been reported to have the potential value to detect pathology accurately in clinical applications. However, comparative analyses of algorithms in the literature have been hindered by the lack of high-quality, rigorously validated, and standardized open databases of heart sound recordings. This paper describes a public heart sound database, assembled for an international competition, the PhysioNet/Computing in Cardiology (CinC) Challenge 2016. The archive comprises nine different heart sound databases sourced from multiple research groups around the world. It includes 2435 heart sound recordings in total collected from 1297 healthy subjects and patients with a variety of conditions, including heart valve disease and coronary artery disease. The recordings were collected from a variety of clinical or nonclinical (such as in-home visits) environments and equipment. The length of recording varied from several seconds to several minutes. This article reports detailed information about the subjects/patients including demographics (number, age, gender), recordings (number, location, state and time length), associated synchronously recorded signals, sampling frequency and sensor type used. We also provide a brief summary of the commonly used heart sound segmentation and classification methods, including open source code provided concurrently for the Challenge. A description of the PhysioNet/CinC Challenge 2016, including the main aims, the training and test sets, the hand corrected annotations for different heart sound states, the scoring mechanism, and associated open source code are provided. In addition, several potential benefits from the public heart sound database are discussed.

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.

Alteration of Ventricular Fibrillation by Flecainide, Verapamil, and Sotalol An Experimental Study

BACKGROUND The purpose of this study was to determine whether the myocardial electrophysiological properties are useful for predicting changes in the ventricular fibrillatory pattern. METHODS AND RESULTS Thirty-two Langendorff-perfused rabbit hearts were used to record ventricular fibrillatory activity with an epicardial multiple electrode. Under control conditions and after flecainide, verapamil, or d,l-sotalol, the dominant frequency (FrD), type of activation maps, conduction velocity, functional refractory period, and wavelength (WL) of excitation were determined during ventricular fibrillation (VF). Flecainide (1.9+/-0.3 versus 2.4+/-0.6 cm, P<0. 05) and sotalol (2.1+/-0.3 versus 2.5+/-0.5 cm, P<0.05) prolonged WL and diminished FrD during VF, whereas verapamil (2.0+/-0.2 versus 1. 7+/-0.2 cm, P<0.001) shortened WL and increased FrD. Simple linear regression revealed an inverse relation between FrD and the functional refractory period (r=0.66, P<0.0001), a direct relation with respect to conduction velocity (r=0.33, P<0.01), and an inverse relation with respect to WL estimated during VF (r=0.49, P<0.0001). By stepwise multiple regression, the functional refractory periods were the only predictors of FrD. Flecainide and sotalol increased the circuit size of the reentrant activations, whereas verapamil decreased it. The 3 drugs significantly reduced the percentages of more complex activation maps during VF. CONCLUSIONS The activation frequency is inversely related to WL during VF, although a closer relation is observed with the functional refractory period. Despite the diverging effects of verapamil versus flecainide and sotalol on the activation frequency, WL, and size of the reentrant circuits, all 3 drugs reduce activation pattern complexity during VF.

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.

Frailty and other geriatric conditions for risk stratification of older patients with acute coronary syndrome.

BACKGROUND Geriatric conditions may predict outcomes beyond age and standard risk factors. Our aim was to investigate a wide spectrum of geriatric conditions in survivors after an acute coronary syndrome. METHODS A total of 342 patients older than 65 years were included. At hospital discharge, 5 geriatric conditions were evaluated: frailty (Fried and Green scores), physical disability (Barthel index), instrumental disability (Lawton-Brody scale), cognitive impairment (Pfeiffer questionnaire), and comorbidity (Charlson and simple comorbidity indexes). The outcomes were postdischarge mortality and the composite of death/myocardial infarction during a 30-month median follow-up. RESULTS Seventy-four (22%) patients died and 105 (31%) suffered from the composite end point. Through univariable analysis, all individual geriatric indexes were associated with outcomes, mainly mortality. Of all of them, frailty using the Green score had the strongest discriminative accuracy (area under the receiver operating characteristic curve 0.76 for mortality). After full adjustment including clinical and geriatric data, the Green score was the only independent predictive geriatric condition (per point; mortality: hazard ratio 1.25, 95% CI 1.15-1.36, P = .0001; composite end point: hazard ratio 1.16, 95% CI 1.09-1.24, P = .0001). A Green score ≥ 5 points was the strongest mortality predictor. The addition of the Green score to the clinical model improved discrimination (area under the receiver operating characteristic curve 0.823 vs 0.846) and significantly reclassified mortality risk (net reclassification improvement 26.3, 95% CI 1.4-43.5; integrated discrimination improvement 4.0, 95% CI 0.8-9.0). The incremental predictive information was even greater over the GRACE score. CONCLUSIONS Frailty captures most of the prognostic information provided by geriatric conditions after acute coronary syndromes. The Green score performed better than the other geriatric indexes.

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.

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.

Papel del índice de Charlson en el pronóstico a 30 días y 1 año tras un infarto agudo de miocardio

Introduccion y objetivos.El indice de Charlson (iCh) ha sido utilizado como variable de ajuste en modelos multivariables como indicador de comorbilidad. Debido a que su valor pronostico per se para complicaciones cardiovasculares tras un infarto agudo de miocardio no ha sido ampliamente evaluado, nos propusimos determinar su valor predictivo para muerte de cualquier causa y/o reinfarto, a 30 dias y 1 ano del evento indice. Pacientes y metodo. Se incluyo a 1.035 pacientes con el diagnostico de infarto (508 con elevacion del segmento ST y 527 sin elevacion del segmento ST). La presencia de eventos se determino a 30 dias (13,9%) y a un ano (26,3%). El iCh se calculo junto con otras variables de valor pronostico en el momento del ingreso, y se establecieron 4 grupos: 1, iCh = 0 (control); 2, iCh = 1; 3, iCh = 2, y 4, iCh ≥ 3. Para el analisis multivariable se utilizo la regresion de riesgos proporcionales de Cox; su poder discriminativo se evaluo mediante el indice C. Resultados. Los riesgos relativos (RR) y el intervalo de confianza [IC] del 95% para las categorias del iCh fueron: a los 30 dias, para la categoria 2, RR = 1,69; IC del 95%, 1,10-2,59; para la 3, RR = 1,78; IC del 95%,1,08-2,92, y para la 4, RR = 1,57; IC del 95%, 0,87-2,83; los valores a 1 ano fueron, para la categoria 2, RR = 1,62; IC del 95%, 1,18-2,23; para la 3, RR = 2,00; IC del 95%, 1,39-2,89, y para la 4, RR = 2,24; IC del 95%, 1,50-3,36. La diferencia en el indice C del modelo con y sin la variable iCh fue 0,765 y 0,750 a los 30 dias y 0,751 y 0,735 a 1 ano. Conclusiones. El iCh proporciono informacion pronostica independiente para muerte y/o reinfarto a los 30 dias y a 1 ano tras el infarto indice. Palabras clave: Infarto agudo de miocardio. Comorbilidad. Indice de Charlson.