Cronobiología de la muerte en insuficiencia cardiaca / Chronobiology of Death in Heart Failure

Introducción y objetivos En la población general, los eventos cardiacos ocurren más frecuentemente durante las primeras horas de la mañana, los lunes y durante el invierno. Sin embargo, la cronobiología de la muerte en la insuficiencia cardiaca no se ha analizado. El objetivo de este estudio es determinar la variabilidad circadiana, de día de la semana y estacional de la mortalidad por cualquier causa en la insuficiencia cardiaca crónica. Métodos Se analizó a todos los pacientes consecutivos seguidos en una unidad de insuficiencia cardiaca desde enero de 2003 a diciembre de 2008. El momento circadiano de la muerte se analizó en intervalos de 6 h y se determinó revisando los informes médicos y mediante información aportada por los familiares del paciente. Resultados De los 1.196 pacientes (media de edad, 69 ± 13 años; el 62% varones), 418 (34,9%) murieron durante un seguimiento medio de 29 ± 21 meses. Los supervivientes eran más jóvenes, tenían mayores índice de masa corporal, fracción de eyección del ventrículo izquierdo, tasa de filtrado glomerular, hemoglobina y natremia y menores puntuaciones de riesgo de Framingham, valores de fracción aminoterminal del propéptido natriurético tipo B, troponina T y uratos. Recibían con más frecuencia tratamiento con antagonistas de los receptores de la angiotensina II , bloqueadores beta, antagonistas de los receptores mineralocorticoideos, digoxina, nitratos, hidralazina, estatinas, diuréticos de asa y tiacidas. El análisis de la variabilidad circadiana y semanal no reveló diferencias significativas entre los intervalos de 6 h o los días de la semana. La mortalidad fue más frecuente durante el invierno (30,6%) que en otras estaciones (p = 0,024).Conclusiones La mortalidad por cualquier causa no sigue un patrón circadiano, pero sí un ritmo estacional, en pacientes con insuficiencia cardiaca. Este hallazgo contrasta con el ritmo circadiano de los eventos cardiovasculares observado en la población general (AU)

Introduction and objectives In the general population, heart events occur more often during early morning, on Mondays, and during winter. However, the chronobiology of death in heart failure has not been analyzed. The aim of this study was to determine the circadian, day of the week, and seasonal variability of all-cause mortality in chronic heart failure. Methods This was an analysis of all consecutive heart failure patients followed in a heart failure unit from January 2003 to December 2008. The circadian moment of death was analyzed at 6-h intervals and was determined by reviewing medical records and by information provided by the relatives. Results Of 1196 patients (mean [standard deviation] age, 69 [13] years; 62% male), 418 (34.9%) died during a mean (standard deviation) follow-up of 29 (21) months. Survivors were younger, had higher body mass index, left ventricular ejection fraction, glomerular filtration rate, hemoglobin and sodium levels, and lower Framingham risk scores, amino-terminal pro-B type natriuretic peptide, troponin T, and urate values. They were more frequently treated with angiotensin receptor blockers, beta-blockers, mineralocorticoids receptor antagonists, digoxin, nitrates, hydralazine, statins, loop diuretics, and thiazides. The analysis of the circadian and weekly variability did not reveal significant differences between the four 6-h intervals or the days of the week. Mortality occurred more frequently during the winter (30.6%) compared with the other seasons (P = .024). Conclusions: All cause mortality does not follow a circadian pattern, but a seasonal rhythm in patients with heart failure. This finding is in contrast to the circadian rhythmicity of cardiovascular events reported in the general population

Prognostic value of increased carbohydrate antigen in patients with heart failure.

AIM: To study the prognostic value of carbohydrate antigen 125 (CA125) and whether it adds prognostic information to N-terminal pro-brain natriuretic peptide (NT-proBNP) in stable heart failure (HF) patients. METHODS: The predictive value of CA125 was retrospectively assessed in 156 patients with stable HF remitted to the outpatient HF unit for monitoring from 2009 to 2011. Patients were included in the study if they had a previous documented episode of HF and received HF treatment. CA125 and NT-proBNP concentrations were measured. The independent association between NT-proBNP or CA125 and mortality was assessed with Cox regression analysis, and their combined predictive ability was tested by the integrated discrimination improvement (IDI) index. RESULTS: The mean age of the 156 patients was 72 ± 12 years. During follow-up (17 ± 8 mo), 27 patients died, 1 received an urgent heart transplantation and 106 required hospitalization for HF. Higher CA125 values were correlated with outcomes: 58 ± 85 KU/L if hospitalized vs 34 ± 61 KU/L if not (P < 0.05), and 94 ± 121 KU/L in those who died or needed urgent heart transplantation vs 45 ± 78 KU/L in survivors (P < 0.01). After adjusting for propensity scores, the highest risk was observed when both biomarkers were elevated vs not elevated (HR = 8.95, 95%CI: 3.11-25.73; P < 0.001) and intermediate when only NT-proBNP was elevated vs not elevated (HR = 4.15, 95%CI: 1.41-12.24; P < 0.01). Moreover, when CA125 was added to the clinical model with NT-proBNP, a 4% (P < 0.05) improvement in the IDI was found. CONCLUSION: CA125 > 60 KU/L identified patients in stable HF with poor survival. Circulating CA125 level adds prognostic value to NT-proBNP level in predicting HF outcomes.

Chronobiology of death in heart failure.

INTRODUCTION AND OBJECTIVES: In the general population, heart events occur more often during early morning, on Mondays, and during winter. However, the chronobiology of death in heart failure has not been analyzed. The aim of this study was to determine the circadian, day of the week, and seasonal variability of all-cause mortality in chronic heart failure. METHODS: This was an analysis of all consecutive heart failure patients followed in a heart failure unit from January 2003 to December 2008. The circadian moment of death was analyzed at 6-h intervals and was determined by reviewing medical records and by information provided by the relatives. RESULTS: Of 1196 patients (mean [standard deviation] age, 69 [13] years; 62% male), 418 (34.9%) died during a mean (standard deviation) follow-up of 29 (21) months. Survivors were younger, had higher body mass index, left ventricular ejection fraction, glomerular filtration rate, hemoglobin and sodium levels, and lower Framingham risk scores, amino-terminal pro-B type natriuretic peptide, troponin T, and urate values. They were more frequently treated with angiotensin receptor blockers, beta-blockers, mineralocorticoids receptor antagonists, digoxin, nitrates, hydralazine, statins, loop diuretics, and thiazides. The analysis of the circadian and weekly variability did not reveal significant differences between the four 6-h intervals or the days of the week. Mortality occurred more frequently during the winter (30.6%) compared with the other seasons (P = .024). CONCLUSIONS: All cause mortality does not follow a circadian pattern, but a seasonal rhythm in patients with heart failure. This finding is in contrast to the circadian rhythmicity of cardiovascular events reported in the general population.

Usefulness of body mass index to characterize nutritional status in patients with heart failure.

The obesity paradox in heart failure (HF) is criticized because of the limitations of body mass index (BMI) in correctly characterizing overweight and obese patients, necessitating a better evaluation of nutritional status. The aim of this study was to assess nutritional status, BMI, and significance in terms of HF survival. Anthropometry and biochemical nutritional markers were assessed in 55 HF patients. Undernourishment was defined as the presence of ≥2 of the following indexes below the normal range: triceps skinfold, subscapular skinfold, arm muscle circumference, albumin, and total lymphocyte count. Patients were also stratified by BMI and followed for a median of 26.7 months. Across BMI strata, no patient was underweight, 31% were normal weight, 42% were overweight, and 27% were obese. Undernourishment was present in 53% of normal-weight patients, 22% of overweight patients, and none of the obese patients (p = 0.001). Undernourished patients had significantly higher mortality (p = 0.009) compared to well-nourished patients. In multivariate analysis, only undernutrition (hazard ratio 3.149, 95% confidence interval 1.367 to 7.253), New York Heart Association functional class (hazard ratio 3.374, 95% confidence interval 1.486 to 7.659), and age (hazard ratio 1.115, 95% confidence interval 1.045 to 1.189) remained in the model. Among nutritional indicators, subscapular skinfold was the best predictor of mortality; patients with subscapular skinfold in the fifth percentile had higher mortality (p = 0.0001). In conclusion, BMI does not indicate true nutritional status in HF. Classifying patients as well nourished or undernourished may improve risk stratification.

[Prognosis of patients admitted in a coronary care unit after resucitating from out-of-hospital sudden cardiac death]. / Pronóstico de los pacientes ingresados en una unidad coronaria después de la recuperación de una muerte súbita de causa cardíaca fuera del hospital.

BACKGROUND AND OBJECTIVE: The aims of the present study were to analyze the prognosis after resuscitation from out-of-hospital sudden cardiac death in patients admitted to the coronary care unit, and to identify the predictor variables of morbi-mortality. PATIENTS AND METHOD: From November 1999 to January 2004 we analyzed 63 patients (47 males) aged 61 +/- 12 years who were admitted to the coronary care unit following successful resuscitation from sudden cardiac death. The clinical and electrocardiographic characteristics were correlated with the mortality and neurological impairment. RESULTS: Thirty-five patients (55.5%) were discharged, while twenty-eight patients (45.5%) died 28 +/- 4 days after admission, most of them during hospitalization. The main underlying disorder was coronary artery disease (80.9%). When survivors and non-survivors were compared, the variables associated with a worse prognosis were diabetes mellitus (68.4% vs 17.1%, P < .02), the presence of valvular heart disease (28.6% vs 0%, p < 0.003), chronic atrial fibrillation (42.9% vs 14.3%, P < .02) and asystole as the initial rhythm observed (42.9% vs 11.4%, P < .01). Multivariate analysis identified asystole as an independent factor of poor prognosis (P < .02). Death was due to severe postanoxic neurological damage in 23 of 28 deaths (82.1%). The remaining 5 patients died due to their underlying cardiac disease (P < .01). The variables associated with neurological damage were out-of hospital resuscitation, delay in beginning resuscitation maneuvers, arrival time > 5 minutes and unconsciousness on admission. CONCLUSIONS: Although many patients survive following resuscitation from out-of-hospital sudden cardiac death, mortality remains high. Neurological impairment is the main cause of mortality. Prognosis is determined by the variables related to the underlying disease, the delay in onset of resuscitation maneuvers and postanoxia cerebral damage.

Pronóstico de los pacientes ingresados en una unidad coronaria después de la recuperación de una muerte súbita de causa cardíaca fuera del hospital / Prognosis of patients admitted in a coronary care unit after resucitating from out-of-hospital sudden cardiac death

Fundamento y objetivo: Los objetivos del presente estudio han sido analizar el pronóstico en pacientes recuperados de una muerte súbita cardíaca extrahospitalaria que ingresaron en la unidad de cuidados intensivos coronarios, así como identificar los factores asociados a la morbimortalidad. Pacientes y método: Analizamos a 63 pacientes consecutivos (47 varones), con una edad media (desviación estándar) de 61 (12) años, que ingresaron entre noviembre de 1999 y enero de 2004 recuperados de una muerte súbita cardíaca y permanecieron en la unidad de cuidados intensivos coronarios. Se examinó la relación de las características clínicas y electrocardiográficas con la mortalidad y las secuelas neurólogicas. Resultados: Sobrevivieron 35 pacientes (55,5%), mientras que 28 (44,5%) fallecieron transcurridos una media de 28 (4) días desde el ingreso, la mayoría en el hospital. El sustrato anatómico principal fue la cardiopatía isquémica (80,9%). En los pacientes que fallecieron, comparados con los que sobrevivieron, las variables que se asociaron a un peor pronóstico fueron la diabetes mellitus (un 68,4 frente al 17,1%; p < 0,02), la presencia de cardiopatía valvular (el 28,6 frente al 0%; p < 0,003), la fibrilación auricular crónica (un 42,9 frente al 14,3%; p < 0,02) y la asistolia como primer ritmo observado (el 42,9 frente al 11,4%; p < 0,01). El análisis multivariable identificó la asistolia como factor independiente de mal pronóstico (p < 0,02). En 23 de los 28 pacientes que fallecieron la muerte fue secundaria a secuelas cerebrales postanóxicas graves (82,1%), mientras que los 5 pacientes restantes fallecieron a consecuencia de su cardiopatía subyacente (p < 0,01). Las variables que se asociaron a daño neurológico fueron la reanimación realizada extrahospitalariamente, el hecho de que el paciente ingresara inconsciente, el tiempo de llegada superior a 5 min y el tiempo de retraso en el inicio de la resucitación cardiopulmonar. Conclusiones: La supervivencia en pacientes recuperados de una muerte súbita cardíaca extrahospitalaria es alta, aunque la mortalidad todavía sigue siendo elevada. Las complicaciones neurológicas son la principal causa de mortalidad. El pronóstico viene determinado por la presencia de factores relacionados con la enfermedad subyacente, el tiempo en iniciar las maniobras de recuperación y la lesión cerebral postanóxica

Background and objective: The aims of the present study were to analyze the prognosis after resuscitation from out-of-hospital sudden cardiac death in patients admitted to the coronary care unit, and to identify the predictor variables of morbi-mortality. Patients and method: From November 1999 to January 2004 we analyzed 63 patients (47 males) aged 61±12 years who were admitted to the coronary care unit following successful resuscitation from sudden cardiac death. The clinical and electrocardiographic characteristics were correlated with the mortality and neurological impairment. Results: Thirty-five patients (55.5%) were discharged, while twenty-eight patients (45.5%) died 28±4 days after admission, most of them during hospitalization. The main underlying disorder was coronary artery disease (80.9%). When survivors and non-survivors were compared, the variables associated with a worse prognosis were diabetes mellitus (68.4% vs 17.1%, P5 minutes and unconsciousness on admission. Conclusions: Although many patients survive following resuscitation from out-of-hospital sudden cardiac death, mortality remains high. Neurological impairment is the main cause of mortality. Prognosis is determined by the variables related to the underlying disease, the delay in onset of resuscitation maneuvers and postanoxia cerebral damage

Utility of contrast-enhanced cardiovascular magnetic resonance (CE-CMR) to assess how likely is an infarct to produce a typical ECG pattern.

OBJECTIVES: For over 50 years, Q-wave myocardial infarction (MI) location has been based on pathologic ECG studies. Although contrast-enhanced magnetic resonance (CE-CMR) is currently the "gold standard" technique for location and quantification of necrotic areas, we found no large study in the literature devoted to establish which ECG patterns corresponds to different MI location detected by CE-CMR. We hypothesized that CE-CMR would be very accurate for evaluating different ECG patterns and its sensitivity (SE) and specificity (SP) for locating MI in different LV areas. METHODS AND RESULTS: CE-CMR/ECG correlation was studied in 48 patients who presented a first MI due to acute coronary syndrome (ACS) with ST-segment elevation and in whom CE-CMR was performed in chronic phase. We evaluated the ECG patterns that best correlated with the 7 prespecified necrotic areas assessed by CE-CMR, 4 in anteroseptal zone (septal, apical/anteroseptal, extensive anterior, and limited anterolateral) and 3 in inferolateral zone (inferior, lateral and inferolateral). The global concordance between CE-CRM and ECG was of 75% and 7 ECG patterns were stablished. CONCLUSION: The capacity of CE-CMR to detect ECG patterns for necrotic area location presents highly acceptable concordance. Thanks to CE-CMR, we defined 7 ECG patterns for MI detection according to the 7 areas of the LV studied. The areas that present more cases with normal ECG are limited anterolateral and the areas of the inferolateral zone.

Concordance of electrocardiographic patterns and healed myocardial infarction location detected by cardiovascular magnetic resonance.

Q-wave myocardial infarction (MI) location is generally based on a pathologic correlation first proposed >50 years ago. Despite the proved reliability of contrast-enhanced cardiovascular magnetic resonance (CE-CMR) imaging to detect and locate infarcted areas, no global study has been conducted with the aim of correlating the electrocardiographic (ECG) patterns of Q-wave MI with infarct location. We studied this correlation in 51 patients with ST-elevation acute coronary syndrome who presented with Q waves or equivalents during MI. Seven preestablished ECG patterns that matched with high specificity to 7 different MI locations as detected by CE-CMR imaging were used to assess its value in clinical practice to locate an infarcted area. There were 4 ECG patterns in the anteroseptal zone (23 patients; septal, apical, and/or anteroseptal, extensive anterior, and limited anterolateral) and 3 ECG patterns in the inferolateral zone (28 patients; lateral, inferior, and inferolateral). In conclusion, (1) the predefined ECG patterns we used matched well (86% global concordance) with their corresponding infarction areas as detected by CE-CMR imaging and have real value in clinical practice, and (2) the RS morphology in lead V(1) is due to lateral MI and the QS morphology in lead aVL is due to mid-anterior and mid-lateral MI. Therefore, the terms posterior and high lateral infarction are incorrect and should be changed to lateral wall and limited anterolateral wall MI.

Evaluation of inflammatory and renal-injury markers in women treated with antibiotics for acute pyelonephritis caused by Escherichia coli.

The evolution and the relationship between inflammatory and renal-injury markers in women with acute uncomplicated pyelonephritis under antimicrobial therapy were investigated in a prospective study. Markers were measured before and 6 and 24 h after the intravenous administration of 1 g of ceftriaxone. Before treatment, the median levels of all markers except the serum creatinine levels were high. Twenty-four hours after the onset of antibiotic treatment, the C-reactive protein (CRP) level continued to be high, while the serum interleukin-6 (IL-6) levels and the urine IL-6, IL-8, albumin, and immunoglobulin G (IgG) levels decreased significantly. In contrast, serum creatinine and tumor necrosis factor alpha levels and urine N-acetyl-beta-glucosaminidase, alpha1-microglobulin, and beta2-microglobulin levels did not change over time. There was a significant correlation between IL-6 and IL-8 levels and urine albumin and IgG levels (urine albumin and IgG levels are glomerular and urinary tract-injury markers) as well as between serum CRP levels and the levels of the tubular-injury markers. In women with acute pyelonephritis, appropriate antibiotic treatment rapidly decreases serum IL-6 levels and urine IL-6 and IL-8 levels, which correlate well with urine albumin and IgG levels.