Manel Azqueta

Prognostic value of serum cytokines in patients with congestive heart failure

BACKGROUND Increased levels of circulating cytokines have been previously reported in patients with congestive heart failure; however, whether they have prognostic implications is still unknown. The aim of this study was to assess the prognostic implications of elevated serum cytokines in patients with heart failure and to identify the predictors of cytokine activation. METHODS AND RESULTS We assessed neurohormonal determinations, circulating cytokines, ejection fraction (EF) and end-diastolic and end-systolic left ventricular lengths in 87 patients (aged 57 +/- 9 years) with left ventricular dysfunction (EF 24% +/- 6%). In 48 patients, we also assessed cytokine receptors. During follow-up (mean, 14 +/- 9 months), 8 patients died and 12 had new heart failure episodes that required hospital admission, 5 of whom underwent heart transplantation. The univariate predictors of these events were serum interleukin-6 (IL-6) (p = 0.00001), New York Heart Association (NYHA) functional class (p = 0.0004), tumor necrosis factor-soluble receptor I (p = 0. 001), atrial natriuretic peptide (p = 0.002), tumor necrosis factor-soluble receptor II (p = 0.004), angiotensin II (p = 0.006), serum interleukin-1 beta (p = 0.01), and plasma renin activity (p = 0.02). Increased serum interleukin-6 (>10 pg/ml) was a significant predictor of death or new heart failure episodes according to the Kaplan-Meier survival method by log-rank test (p = 0.004). By Cox regression analysis, serum IL-6 (p = 0.0005) and the NYHA functional class (p = 0.005) were identified as independent predictors of prognosis. CONCLUSIONS In patients with congestive heart failure, increased serum IL-6 was identified as a powerful independent predictor of the combined end point: death, new heart failure episodes, and need for heart transplantation.

Serum interleukin-6 in congestive heart failure secondary to idiopathic dilated cardiomyopathy

Increased serum interleukin-6 (IL-6) was associated with a higher incidence of New York Heart Association functional classes III to IV and worse left ventricular function during follow-up. Patients with elevated serum IL-6 had poor prognosis. These results reinforce the concept that increased serum IL-6 may also play an important role in disease progression.

Chagas Cardiomiopathy: The Potential of Diastolic Dysfunction and Brain Natriuretic Peptide in the Early Identification of Cardiac Damage

Introduction Chagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the role of diastolic dysfunction, abnormal myocardial strain and elevated brain natriuretic peptide (BNP) in the early identification of cardiac involvement in Chagas disease. Methodology/Principal Findings Fifty-four patients divided into 3 groups—group 1 (undetermined form: positive serology without ECG or 2D-echocardiographic abnormalities; N = 32), group 2 (typical ECG abnormalities of Chagas disease but normal 2D-echocardiography; N = 14), and group 3 (regional wall motion abnormalities, left ventricular [LV] end-diastolic diameter >55 mm or LV ejection fraction <50% on echocardiography; N = 8)—and 44 control subjects were studied. Patients with significant non-cardiac diseases, other heart diseases and previous treatment with benznidazol were excluded. The median age was 37 (20–58) years; 40% were men. BNP levels, longitudinal and radial myocardial strain and LV diastolic dysfunction increased progressively from group 1 to 3 (p for trend <0.01). Abnormal BNP levels (>37 pg/ml) were noted in 0%, 13%, 29% and 63% in controls and groups 1 to 3, respectively. Half of patients in the undetermined form had impaired relaxation patterns, whereas half of patients with ECG abnormalities suggestive of Chagas cardiomyopathy had normal diastolic function. In group 1, BNP levels were statistically higher in patients with diastolic dysfunction as compared to those with normal diastolic function (27±26 vs. 11±8 pg/ml, p = 0.03). Conclusion/Significance In conclusion, the combination of diastolic function and BNP measurement adds important information that could help to better stratify patients with Chagas disease.

Long-term effect of cardiac resynchronization therapy on functional mitral valve regurgitation.

Cardiac resynchronization therapy (CRT) has been shown to reduce functional mitral regurgitation (MR). The aims of this study were to analyze the underlying mechanisms leading to this reduction and to identify the best candidates with functional MR for this therapy. Changes in mitral geometry, left ventricular (LV) remodeling, and LV synchrony were studied in patients who underwent CRT acutely and at 6- and 12-month follow-up. Of 151 patients (mean age 69 +/- 9 years, 82% men) who underwent CRT, 57 (38%) had nontrivial MR (regurgitant orifice area > or =10 mm(2)). The median reduction of MR with CRT was 18% acutely and 38% at 12-month follow-up. CRT induced an acute improvement in LV systolic function (LV dP/dt from 508 +/- 143 to 700 +/- 249 mm Hg, p <0.05) and a reduction in dyssynchrony (interventricular delay from 51 +/- 31 to 29 +/- 27 ms, p <0.05). At 12-month follow-up, additional reverse global and local LV remodeling (LV end-systolic volume from 183 +/- 77 to 151 +/- 50 ml, tenting area from 3.36 +/- 0.98 to 2.78 +/- 0.75 cm, p <0.05 for both) and a reduction in LV dyssynchrony (septal-lateral delay from 90 +/- 63 to 53 +/- 42 ms, p <0.05) were found. Significant reductions in MR were found in 28 patients (49%) and similarly observed in either ischemic MR or functional MR of other causes. Baseline mitral tenting area was the strongest predictor of significant MR reduction with CRT. In conclusion, CRT induced acute and sustained reductions in functional MR in almost 50% of patients by initially improving LV systolic function and dyssynchrony; long-term reverse LV remodeling contributed to this sustained effect. Patients with larger mitral valve tenting areas are less amenable to benefit from CRT.

Efficacy and Safety of Fosfomycin Plus Imipenem as Rescue Therapy for Complicated Bacteremia and Endocarditis Due to Methicillin-Resistant Staphylococcus aureus: A Multicenter Clinical Trial

BACKGROUND There is an urgent need for alternative rescue therapies in invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We assessed the clinical efficacy and safety of the combination of fosfomycin and imipenem as rescue therapy for MRSA infective endocarditis and complicated bacteremia. METHODS The trial was conducted between 2001 and 2010 in 3 Spanish hospitals. Adult patients with complicated MRSA bacteremia or endocarditis requiring rescue therapy were eligible for the study. Treatment with fosfomycin (2 g/6 hours IV) plus imipenem (1 g/6 hours IV) was started and monitored. The primary efficacy endpoints were percentage of sterile blood cultures at 72 hours and clinical success rate assessed at the test-of-cure visit (45 days after the end of therapy). RESULTS The combination was administered in 12 patients with endocarditis, 2 with vascular graft infection, and 2 with complicated bacteremia. Therapy had previously failed with vancomycin in 9 patients, daptomycin in 2, and sequential antibiotics in 5. Blood cultures were negative 72 hours after the first dose of the combination in all cases. The success rate was 69%, and only 1 of 5 deaths was related to the MRSA infection. Although the combination was safe in most patients (94%), a patient with liver cirrhosis died of multiorgan failure secondary to sodium overload. There were no episodes of breakthrough bacteremia or relapse. CONCLUSIONS Fosfomycin plus imipenem was an effective and safe combination when used as rescue therapy for complicated MRSA bloodstream infections and deserves further clinical evaluation as initial therapy in these infections.

Relation of plasma brain natriuretic peptide levels on admission for ST-elevation myocardial infarction to left ventricular end-diastolic volume six months later measured by both echocardiography and cardiac magnetic resonance.

The main objective of this study was to investigate the relation between brain natriuretic peptide (BNP) levels within the first 96 hours after ST-segment elevation acute myocardial infarction (STEMI) and the development of left ventricular (LV) dilatation at 6-month follow-up. Eighty-two patients with first STEMIs, reperfused within 12 hours of symptom onset, were prospectively included. Plasma BNP was determined on admission and at 1- and 6-month follow-up. Clinically significant LV dilatation, defined as a >20% increase in LV end-diastolic volume at 6-month follow-up, was assessed using echocardiography and cardiac magnetic resonance. Thirty-two percent of patients developed clinically significant LV dilatation. BNP values on admission and at follow-up were significantly higher in patients who developed clinically significant LV dilatation at 6 months (182 +/- 117 vs 106 +/- 91 pmol/ml). After adjusting for age, infarct size, E-wave deceleration time, and the LV ejection fraction, BNP on admission was an independent predictor of LV dilatation, whether assessed by echocardiography (B = 0.075, p = 0.04) or cardiac magnetic resonance (B = 0.085, p = 0.04). In conclusion, high BNP levels on admission and at follow-up predict LV dilatation after STEMI. The early determination of plasma BNP upon admission for STEMI could be helpful in identifying patients at higher risk for LV dilatation, in whom aggressive management is warranted.

Usefulness of Echocardiography in Preparticipation Screening of Competitive Athletes

INTRODUCTION AND OBJECTIVES Despite the established diagnostic value of the electrocardiogram in preparticipation screening of athletes, some cardiac structural changes can be missed, particularly in early disease stages. The aim of this study was to evaluate the prevalence of cardiac structural changes via the systematic use of echocardiography in preparticipation screening of competitive athletes. METHODS Professional athletes or participants in a competitive athletic program underwent a screening that included family and personal medical history, physical examination, electrocardiography, exercise testing, and Doppler echocardiography. RESULTS A total of 2688 athletes (67% men; mean age [standard deviation], 21 [10] years) were included. Most of the echocardiographic evaluations (92.5%) were normal and only 203 (7.5%) showed changes; the most frequent change was left ventricular hypertrophy, seen in 50 athletes (1.8%). Cessation of athletic activity was indicated in 4 athletes (0.14%): 2 for hypertrophic cardiomyopathy (electrocardiography had shown changes that did not meet diagnostic criteria), 1 pectus excavatum with compression of the right ventricle, and 1 significant pulmonary valve stenosis; the rest of the changes did not entail cessation of athletic activity and only indicated periodic monitoring. CONCLUSIONS Although rare, some cardiac structural changes can be missed on physical examination and electrocardiography; in contrast, they are easily recognized with echocardiography. These findings suggest the use of echocardiography in at least the first preparticipation screening of competitive athletes to improve the effectiveness of programs aimed at preventing sudden death in athletes.

Influencia de la cardiopatía subyacente en la respuesta a la terapia de resincronización cardiaca

INTRODUCTION AND OBJECTIVES Little is known about how responses to cardiac resynchronization therapy (CRT) are affected by the nature of the underlying cardiopathy. The aim of this study was to investigate how cardiopathy etiology influences the effect of CRT on reverse left ventricular remodeling. METHODS The study included 106 patients with left ventricular systolic dysfunction and left bundle branch block (LBBB) who were receiving CRT. Clinical and echocardiographic investigations were performed at baseline before implantation and at 6 and 12 month follow-up to determine left ventricular diameter, volume and systolic function, and to quantify mitral regurgitation. RESULTS During follow-up, it was observed that CRT reduced left ventricular volume and diameter, increased left ventricular ejection fraction (LVEF), and reduced mitral regurgitation severity irrespective of the etiology of the cardiopathy. In patients with ischemic dilated cardiomyopathy, LVEF increased by 34% and end-diastolic and end-systolic volumes decreased by 4% and 12%, respectively; in those with idiopathic dilated cardiomyopathy, LVEF increased by 38% and end-diastolic and end-systolic volumes decreased by 13% and 19%, respectively (P=NS for ischemic vs. non-ischemic disease). Nor were differences observed between the groups in clinical outcome: 74% of the ischemic group responded compared with 62% of the non-ischemic group (P=NS). CONCLUSIONS At 12-month follow-up, patients with left ventricular systolic dysfunction and LBBB treated by CRT showed clinical improvements and demonstrated reverse ventricular remodeling, irrespective of the etiology of their cardiopathy.Introduccion y objetivos La influencia del tipo de cardiopatia en la respuesta a la terapia de resincronizacion cardiaca (TRC) es poco conocida. El objetivo de este estudio fue analizar el efecto de la TRC en el remodelado, en funcion de la etiologia de la cardiopatia subyacente. Metodos Se incluyo a 106 pacientes con disfuncion sistolica del ventriculo izquierdo (VI) y bloqueo de rama izquierda del haz de His (BRIHH) tratados con TRC. Se les realizo una evaluacion clinica y ecocardiografica para estudiar los diametros, los volumenes y la funcion sistolica del VI y cuantificar la insuficiencia mitral, antes del implante y a los 6 y los 12 meses de seguimiento. Resultados La TRC indujo en el seguimiento una reduccion de los volumenes y diametros ventriculares, aumento la fraccion de eyeccion (FE) y se redujo la insuficiencia mitral independientemente de la etiologia de la cardiopatia: los pacientes isquemicos (MCD-CI) incrementaron la FE del VI (FEVI) un 34% y los volumenes telediastolico y telesistolico se redujeron en el 4 y el 12% frente a un incremento de la FE del 38% y una reduccion de volumenes del 13 y el 19% en los pacientes con miocardiopatia dilatada idiopatica (MCD) (sin diferencia significativa entre MCD-CI y MCD). Tampoco se encontraron diferencias en el numero de respondedores clinicos: el 74% en los pacientes con MCD-CI y el 62% de los portadores de una MCD (sin diferencia significativa). Conclusiones A los 12 meses de seguimiento, los pacientes con disfuncion sistolica del VI y BRIHH tratados con TRC presentaron mejoria clinica y un remodelado ventricular inverso independientemente de la etiologia de su cardiopatia.

Remodelado ventricular izquierdo tras ablación septal percutánea con alcohol en pacientes con miocardiopatía hipertrófica obstructiva: estudio ecocardiográfico

Evaluamos el impacto de la reduccion de la obstruccion en el tracto de salida del ventriculo izquierdo tras la ablacion septal percutanea con alcohol sobre la hipertrofia y el remodelado del ventriculo izquierdo (VI). Pacientes y metodo. Se incluyo a 20 pacientes con miocardiopatia hipertrofica tratados con ablacion septal percutanea. Se realizo ecocardiograma Doppler en situacion basal, inmediatamente despues de la ablacion septal percutanea y a los 3 y 12 meses de seguimiento, en el que se midieron los diametros y grosores del VI y del gradiente de presion en el tracto de salida del ventriculo izquierdo. Resultados. Inmediatamente despues de la ablacion septal percutanea, el gradiente de presion en el tracto de salida del VI disminuyo de 63,0 ± 27,7 a 28,2 ± 24,7 mmHg (p < 0,001), sin que se apreciaran cambios significativos en las dimensiones del VI. Doce meses despues se observo un incremento en los diametros telediastolico (de 47,1 ± 4,9 a 50,8 ± 4,5 mm; p < 0,01) y telesistolico del VI (de 27,1 ± 3,0 a 33,7 ± 4,6 mm; p < 0,01) y una reduccion en los grosores del septo (de 19,5 ± 4,0 a 15,5 ± 2,7 mm; p < 0,01) y de la pared posterior del VI (de 14,0 ± 2,2 a 12,9 ± 1,3 mm; p < 0,01). Los volumenes telediastolico y telesistolico del VI aumentaron (de 106,4 ± 26,9 a 123,1 ± 28,7 ml; p < 0,01, y de 50,2 ± 17,3 a 56,7 ± 18,3 ml; p < 0,01, respectivamente), sin que se observaran cambios en la fraccion de eyeccion del VI. La reduccion del gradiente de presion en el tracto de salida del ventriculo izquierdo observada a los 12 meses de la ablacion septal percutanea se correlaciono de manera significativa con el incremento del diametro telesistolico del VI (r = 0,63; p < 0,01). Conclusiones. La reduccion de la obstruccion en el tracto de salida del ventriculo izquierdo en pacientes con miocardiopatia hipertrofica tratados con ablacion septal percutanea se acompana de un incremento de los diametros y volumenes del VI en el seguimiento. Esto indica el desarrollo de un remodelado cardiaco y de una regresion en la hipertrofia del VI de estos pacientes que podria contribuir a su mejoria sintomatica

Bases anatomopatológicas de la disfunción ventricular latente en diabéticos insulinodependientes

Introduccion y objetivos La historia natural dela miocardiopatia diabetica no esta bien definida,debido principalmente a la comun asociacion conenfermedad coronaria e hipertension arterial. Dadoque estas dos entidades son infrecuentes en los pacientesjovenes, estos constituyen un modelo adecuadopara el estudio de la miocardiopatia diabeticaen sus fases incipientes. Pacientes y metodos Se estudiaron 33 pacientesafectados de diabetes mellitus tipo I sin antecedentesde hipertension arterial ni enfermedad coronaria.Su edad media era de 28 ± 8 anos (rango, 18-46anos) y 14 eran varones. Resultados En el ecocardiograma se observo unventriculo izquierdo de tamano normal y sin anomaliasde la motilidad segmentaria, excepto en uncaso. En la ventriculografia isotopica se detectouna fraccion de eyeccion basal del 56,5 ± 6,6% queaumento al 63 ± 7,4% (p Conclusiones La disfuncion ventricular latentees un hallazgo frecuente en los pacientes diabeticosjovenes asintomaticos, y esta no es secundaria aaterosclerosis coronaria ni a enfermedad de pequenovaso. En este grupo de pacientes las anomaliashistologicas son constantes y se manifiestan por fibrosisintersticial, hipertrofia celular, miocitolisis ydepositos lipidicos.