Combined use of tissue Doppler imaging and natriuretic peptides as prognostic marker in asymptomatic aortic stenosis.

INTRODUCTION: Tissue Doppler imaging (TDI) and N-terminal-pro-Brain Natriuretic Peptide (NT-proBNP) provides useful non-invasive information about left ventricle filling pressures and both have demonstrated to be a prognostic marker in some valve disease as aortic stenosis (AS). OBJECTIVES: To assess the clinical value of combined TDI and NT-proBNP information in asymptomatic AS patients. MATERIAL AND METHODS: Prospective study of 350 initially asymptomatic moderate to severe AS patients with: Mean aortic valve area 0.8 (0.3) cm2, mean gradient 45(13) mmHg, ejection fraction 61 (9) %. Mean age: 74.6 (4.3) years. In all patients were determined NT-proBNP in the serum and TDI parameters the lateral mitral annulus. We considered clinical event the admission in the hospital due to symptoms related to AS (angina, heart failure or syncope) as well as surgical treatment or mortality. RESULTS: After a mean follow-up of 29 (10) months, 165 (47%) patients suffered some clinical event. In order to predict clinical events, Bootstrap analysis determined the best cut-point value: E/E' ratio higher than 13 and NT-proBNP higher than 515pg/mL. E/E' ratio provides more specificity (78.9% vs 55.9%) and NT-proBNP provides more sensitivity (76.6% vs 43.7%). Combined use of both parameters provides the best prognostic information (sensitivity 75.6%, specificity 67.2%, negative predictive value 82.1%, positive predictive value 57.5%, accuracy 71.4%). CONCLUSION: Combined use of TDI and natriuretic peptides information provides incremental prognostic value and is a useful tool to predict the prognosis in asymptomatic AS patients.

Clinical value of ankle-brachial index in asymptomatic aortic stenosis patients.

BACKGROUND AND AIM OF THE STUDY: The study aim was to assess the prevalence and clinical value of the pathological ankle-brachial index (ABI) in asymptomatic aortic stenosis (AS) patients. METHODS: This prospective study included 203 asymptomatic AS patients, with a mean follow up of 18 ± 10.6 months. Six-minute walk tests (6MWT) and ABI measurements were performed when patients were included in the study. Study events were defined as death, hospital admission due to related symptoms, or a need for surgery. RESULTS: A total of 198 patients (95 females, 103 males; mean age 74.6 ± 9.5 years) completed the study. An abnormal ABI was found in 35.8%. Mean (± SD) values were: peak velocity Vmax 4.1 ± 0.8 m/s; maximum/mean gradient 70.5 ± 25.1/43.3 ± 16.3 mmHg; aortic valve area 0.8 ± 0.7 cm2; indexed aortic valve area 0.4 ± 0.1 cm2/m2. A pathological ABI was associated with diabetes (p = 0.01), previous peripheral vascular disease (p = 0.04) and previous stroke (p = 0.04). In multivariate analyses, diabetes was an independent factor related to pathological ABI (relative risk 1.71, 95% CI 1.22-2.19). Patients with a pathological ABI walked less in the 6MWT (263.9 m versus 328.3; p = 0.002), but did not present a worse prognosis at follow up (p = NS). CONCLUSION: Among asymptomatic AS patients, 35.8% had an abnormal ABI and this was related to previous diabetes. These patients walked less in the 6MWT but did not have a worse prognosis at follow up.

Effect of correction of anemia on echocardiographic and clinical parameters in patients with aortic stenosis involving a three-cuspid aortic valve and normal left ventricular ejection fraction.

The objective of the study is to investigate the impact of anemia (defined as hemoglobin concentration of <12 g/dl in women and 13 g/dl in men) on prognosis and to study the effect of recovery from anemia on echocardiographic and clinical parameters in patients with aortic stenosis (AS). This was a prospective study in 315 patients with moderate or severe AS. Patients with anemia received oral iron (ferrous sulfate with mucoproteose, 160 mg iron/day) and erythropoietin, if needed, or intravenous iron, if necessary. The following tests were performed before and after normalization of hemoglobin values: echocardiogram, 6-minute walk test, N-terminal B-type natriuretic peptide, and measures of depression, cognitive impairment, and dependence. Patient mean age was 74 years (SD 9). Mean follow-up was 25 months (SD 8). Anemia prevalence in the overall group was 22% (n = 70). Patients who are anemic had a higher rate of complications at follow-up (mortality, hospital admission, or need for valve procedure; 80% vs 62%, p = 0.009). In total, 89% of patients recovered from anemia, with a mean time to recovery of 4.6 weeks (SD 1.4). Improvements were observed on echocardiographic parameters of peak velocity (4.1 to 3.7 m/s, p = 0.02) and mean gradient (44 to 35 mm Hg, p = 0.02). Performance on the 6-minute walk test improved from 235 to 303 m (p <0.001). Median N-terminal B-type natriuretic peptide value decreased from 612 to 189 pg/dl (p <0.001). In conclusion, patients with AS and anemia have a worse prognosis than those without anemia. Resolution of anemia is associated with improvements in echocardiographic parameters and functional status, suggesting that treatment of iron deficiency is a relevant option in the management of patients with AS, particularly in nonoperable cases.

Prognostic value of NT-proBNP and an adapted monin score in patients with asymptomatic aortic stenosis.

INTRODUCTION AND OBJECTIVES: Our objective was to assess the prognostic value of NT-proBNP in patients with asymptomatic moderate/severe aortic stenosis and to validate an adapted Monin score using natriuretic peptide levels in our setting. METHODS: Prospective study of 237 patients with degenerative asymptomatic moderate/severe aortic stenosis. NT-proBNP was determined in all patients, who were then followed up clinically. The adapted Monin score was defined as follows: (peak velocity [m/s]×2)+(logn NT-proBNP×1.5)(+1.5 if woman). A clinical event was defined as surgery, hospital admission due to angina, heart failure or syncope, or death. RESULTS: A total of 51% were women, and the mean age was 74 years. Mean (SD) echocardiographic values were as follows: peak velocity 4.14 (0.87) m/s; mean gradient, 43.2 (16.0) mmHg; aortic valve area, 0.87 (0.72) cm(2), and aortic valve area index, 0.49 (0.14) cm(2)/m(2). The median NT-pro-BNP value was 490.0 [198.0-1312.0] pg/mL. There were 153 events during follow-up (median 18 months). The optimum NT-proBNP cut-point was 515 pg/mL, giving event-free survival rates at 1 and 2 years of 93% and 57%, respectively, in patients with NT-proBNP <515 pg/mL compared with 50% and 31% in those with NT-proBNP >515 pg/mL. Patients were divided into quartiles based on the Monin score. Event-free survival at 1 and 2 years was 87% and 79% in the first quartile, compared with 45% and 28% in the fourth quartile, respectively. CONCLUSIONS: NT-proBNP determination provides prognostic information in patients with asymptomatic moderate/severe aortic stenosis. The adapted Monin score is useful in our setting and allows a more precise prognosis than does the use of NT-proBNP alone.

Valor pronóstico de la NT-proBNP y adaptación de la puntuación de Monin en pacientes con estenosis aórtica asintomática / Prognostic value of NT-proBNP and an adapted monin score in patients with asymptomatic aortic stenosis

Introducción y objetivos. Los objetivos del estudio son valorar el papel de la NT-proBNP en la valoración pronóstica de los pacientes asintomáticos con estenosis aórtica moderada-grave y validar una adaptación de la puntuación de Monin a nuestra población. Métodos. Estudio prospectivo de 237 pacientes con estenosis aórtica degenerativa moderada-grave asintomática. Se determinó la NT-proBNP y se realizó un seguimiento clínico a todos los pacientes. Se calculó una adaptación de la puntuación de Monin como: (velocidad máxima [m/s] × 2) + (logn NT-proBNP × 1,5) (+ 1,5 si mujer). Se definió evento clínico como necesidad de cirugía valvular, ingreso hospitalario o muerte. Resultados. El 51% eran mujeres, con una media de edad de 74 años. Datos ecocardiográficos: velocidad máxima, 4,14 ± 0,87 m/s; gradiente medio, 43,2 ± 16,0 mmHg; área valvular aórtica, 0,87 ± 0,72 cm2; índice de área valvular aórtica, 0,49 ± 0,14 cm2/m2. La mediana de NT-proBNP fue 490,0 [198,0-1.312,0] pg/ml. Durante el seguimiento (mediana, 18 meses) 153 pacientes sufrieron eventos. El punto óptimo de corte de NT-proBNP fue 515 pg/ml, y se observaron supervivencias libres de eventos a 1 y 2 años del 93 y el 57% de los pacientes con NT-proBNP < 515 pg/ml frente al 50 y el 31% cuando la NT-proBNP era > 515 pg/ml. Se dividió a los pacientes en cuartiles de la puntuación de Monin. Las supervivencias libres de eventos a 1 y 2 años fueron del 87 y el 79% en el primer cuartil, frente al 45 y el 28% en el cuarto cuartil. Conclusiones. La NT-proBNP ofrece información pronóstica de pacientes asintomáticos con estenosis aórtica moderada-grave. La puntuación descrita por Monin es adaptable a nuestra población y mejora el valor pronóstico de la NT-proBNP sola (AU)

Introduction and objectives. Our objective was to assess the prognostic value of NT-proBNP in patients with asymptomatic moderate/severe aortic stenosis and to validate an adapted Monin score using natriuretic peptide levels in our setting. Methods. Prospective study of 237 patients with degenerative asymptomatic moderate/severe aortic stenosis. NT-proBNP was determined in all patients, who were then followed up clinically. The adapted Monin score was defined as follows: (peak velocity [m/s]×2)+(logn NT-proBNP×1.5)(+1.5 if woman). A clinical event was defined as surgery, hospital admission due to angina, heart failure or syncope, or death. Results. A total of 51% were women, and the mean age was 74 years. Mean (SD) echocardiographic values were as follows: peak velocity 4.14 (0.87) m/s; mean gradient, 43.2 (16.0) mmHg; aortic valve area, 0.87 (0.72) cm2, and aortic valve area index, 0.49 (0.14) cm2/m2. The median NT-pro-BNP value was 490.0 [198.0-1312.0] pg/mL. There were 153 events during follow-up (median 18 months). The optimum NT-proBNP cut-point was 515 pg/mL, giving event-free survival rates at 1 and 2 years of 93% and 57%, respectively, in patients with NT-proBNP <515 pg/mL compared with 50% and 31% in those with NT-proBNP >515 pg/mL. Patients were divided into quartiles based on the Monin score. Event-free survival at 1 and 2 years was 87% and 79% in the first quartile, compared with 45% and 28% in the fourth quartile, respectively. Conclusions. NT-proBNP determination provides prognostic information in patients with asymptomatic moderate/severe aortic stenosis. The adapted Monin score is useful in our setting and allows a more precise prognosis than does the use of NT-proBNP alone (AU)

Phenotype and genotype characterization and twin association in patients with Anderson-Fabry cardiomyopathy.

Anderson-Fabry disease (FD), an X-linked recessive lysosomal storage disorder caused by a deficiency of α-galactosidase A (α-Gal A) activity, is associated with cardiac manifestations including arrhythmias, valvular abnormalities, and cardiomyopathy. Early initiation of enzyme replacement therapy (ERT) may have the potential to delay the underlying clinical outcomes in patients with FD. Clinical electrocardiogram (ECG) and echocardiography were used to characterize the cardiomyopathy. Diagnosis of FD was performed by measuring the α-Gal A activity in plasma and mutation analysis by direct sequencing using capillary electrophoresis. We identified four adult hemizygous male patients with cardiomyopathy and other symptoms related to FD; two of them were monozygotic twins. In all cases, ECG and echocardiography showed severe left ventricular (LV) hypertrophy. Some years later, all patients showed typical symptoms of FD, including angiokeratomas and neurological, renal, gastrointestinal, and ocular involvement. A deficiency of α-Gal A activity and point mutations in exon 5 of the GLA gene were detected in all patients. ERT (agalsidase-alfa) was administered every other week as a 0.2 mg/kg intravenous infusion over 40 min. In conclusion, these findings highlight the importance of screening middle-aged patients with LV hypertrophy for the early detection of FD, particularly in direct-line relatives such as twins.

Nuevos predictores de evolución a bloqueo auriculoventricular en pacientes con bloqueo bifascicular / Novel predictors of progression of atrioventricular block in patients with chronic bifascicular block

Introducción y objetivos. Los pacientes con bloqueo bifascicular (BBF) pueden evolucionar a bloqueo auriculoventricular (BAV) avanzado, especialmente en presencia de síncope o intervalo HV prolongado. Otras variables podrían ayudar a definir qué pacientes se beneficiarán de un marcapasos (MP) profiláctico. Métodos. Desde 1998 hasta 2006, hemos estudiado prospectivamente a 263 pacientes consecutivos con BBF en un solo centro. Se analizaron variables clínicas, electrocardiográficas y electrofisiológicas predictoras de evolución a BAV significativo (segundo y tercer grado). Se implantaron dispositivos de estimulación siguiendo las guías de la Sociedad Europea de Cardiología. Los MP fueron programados en modo VVI con frecuencia mínima de 40 lat/min. Se definió necesidad de MP la presencia de BAV significativo o de estimulación ventricular > 10%. Resultados. Se incluyó a 249 pacientes (media de edad, 73,4 ± 9,3 años; 82 mujeres). Tras una mediana de seguimiento de 4,5 (2,16-6,41) años, se observó necesidad de MP en 102 pacientes, 45 por estimulación > 10% y 57 por BAV significativo. Las variables que predijeron la necesidad de MP fueron presencia de síncope o presíncope (hazard ratio [HR] = 2,06; intervalo de confianza [IC] del 95%, 1,03-4,12), anchura QRS > 140 ms (HR = 2,44; IC del 95%, 1,59-3,76), la insuficiencia renal (HR = 1,86; IC del 95%, 1,22-2,83) y un intervalo HV > 64 ms (HR = 6,6; IC del 95%, 4,04-10,80). La asociación de los cuatro factores mostró una probabilidad de necesitar el MP del 95% al año de seguimiento. Conclusiones. La clínica sincopal/presincopal, el QRS > 140 ms, la insuficiencia renal y el intervalo HV > 64 ms son predictores independientes de evolución a BAV en pacientes con BBF (AU)

Introduction and objectives. Patients with chronic bifascicular block (BFB) can progress to advanced atrioventricular block (AVB), especially when syncope or a prolonged HV interval is present. It is possible that other variables could help identify patients who would benefit from prophylactic pacemaker implantation. Methods. The study involved 263 consecutive BFB patients seen at a single center between 1998 and 2006. Clinical, electrocardiographic and electrophysiologic variables were analyzed to identify predictors of progression to significant AVB (i.e. second or third grade). Cardiac pacemakers were implanted in accordance with European Society of Cardiology guidelines. Pacemakers were programmed in the VVI mode with a minimum frequency of 40 beats/min. A pacemaker was required if there was significant AVB or a ventricular pacing percentage >10%. Results. In total, the study included 249 patients (mean age, 73.4±9.3 years, 82 female). After a median follow-up period of 4.5 years (2.16-6.41 years), a pacemaker was required by 102 patients: 45 had a ventricular pacing percentage >10% and 57 had significant AVB. Factors predictive of the need for a pacemaker were: the presence of syncope or presyncope (hazard ratio [HR]=2.06; 95% confidence interval [CI], 1.03-4.12), QRS width >140 ms (HR=2.44; 95% CI, 1.59-3.76), renal failure (HR=1.86; 95% CI, 1.22-2.83), and an HV interval >64 ms (HR=6.6; 95% CI, 4.04-10.80). The presence of all four risk factors was associated with a 95% probability of needing a pacemaker within 1 year of follow-up. Conclusions. The presence of syncope or presyncope, a QRS width >140 ms, renal failure, and an HV interval >64 ms were independent predictors of progression to AVB in patients with BFB (AU)

[Novel predictors of progression of atrioventricular block in patients with chronic bifascicular block]. / Nuevos predictores de evolución a bloqueo auriculoventricular en pacientes con bloqueo bifascicular.

INTRODUCTION AND OBJECTIVES: Patients with chronic bifascicular block (BFB) can progress to advanced atrioventricular block (AVB), especially when syncope or a prolonged HV interval is present. It is possible that other variables could help identify patients who would benefit from prophylactic pacemaker implantation. METHODS: The study involved 263 consecutive BFB patients seen at a single center between 1998 and 2006. Clinical, electrocardiographic and electrophysiologic variables were analyzed to identify predictors of progression to significant AVB (i.e. second or third grade). Cardiac pacemakers were implanted in accordance with European Society of Cardiology guidelines. Pacemakers were programmed in the VVI mode with a minimum frequency of 40 beats/min. A pacemaker was required if there was significant AVB or a ventricular pacing percentage >10%. RESULTS: In total, the study included 249 patients (mean age, 73.4+/-9.3 years, 82 female). After a median follow-up period of 4.5 years (2.16-6.41 years), a pacemaker was required by 102 patients: 45 had a ventricular pacing percentage >10% and 57 had significant AVB. Factors predictive of the need for a pacemaker were: the presence of syncope or presyncope (hazard ratio [HR]=2.06; 95% confidence interval [CI], 1.03-4.12), QRS width >140 ms (HR=2.44; 95% CI, 1.59-3.76), renal failure (HR=1.86; 95% CI, 1.22-2.83), and an HV interval >64 ms (HR=6.6; 95% CI, 4.04-10.80). The presence of all four risk factors was associated with a 95% probability of needing a pacemaker within 1 year of follow-up. CONCLUSIONS: The presence of syncope or presyncope, a QRS width >140 ms, renal failure, and an HV interval >64 ms were independent predictors of progression to AVB in patients with BFB.

[Prevalence of obstructive sleep apnea syndrome in patients with sick sinus syndrome]. / Prevalencia del síndrome de apnea obstructiva del sueño en pacientes con disfunción sinusal.

INTRODUCTION AND OBJECTIVES: Sleep apnea-hypopnea syndrome (SAHS) has been associated with different cardiovascular diseases. It may even be implicated in the pathophysiology of sick sinus syndrome (SSS). However, the precise relationship between the two syndromes is still unknown. We investigated the prevalence of SAHS in patients diagnosed with SSS. PATIENTS AND METHOD: Between June 2002 and December 2004, 38 consecutive patients who were diagnosed with SSS by 24-hour Holter monitoring were studied prospectively in our institution. All patients were asked about symptoms of SAHS, and underwent polysomnography out of hospital using a validated monitor. RESULTS: The patients' mean age was 67 (10) years, 68% were male, and 58% were hypertensive. Holter monitoring demonstrated a maximum heart rate of 87 (6) beats/min, a minimum of 35 (3) beats/min, and a mean of 48 (3) beats/min. Some 24 (63%) patients required pacemaker implantation because of symptomatic SSS. Overall, 39% of patients had symptoms suggestive of SAHS (i.e., an Epworth index or EI>9). Polysomnography showed that only 13% of patients had a normal apnea-hypopnea index (AHI) and that 31.6% (95% CI, 16.8%-46.4%) had SAHS (i.e., AIH>10 and EI>9). CONCLUSIONS: Given that the prevalence of SAHS in the general population is around 3%, our results indicate that it is ten-fold higher in patients with SSS than in the general population. This observation indicates that there may be a relationship between the two syndromes.

Prevalencia del síndrome de apnea obstructiva del sueño en pacientes con disfunción si / Prevalence of obstructive sleep apnea syndrome in patients with sick sinus syndrome

Introducción y objetivos. El síndrome de apnea-hipopnea del sueño (SAHS) ha sido relacionado con varias enfermedades cardiovasculares. Podría incluso estar implicado en la etiopatogenia de la disfunción sinusal (DS), aunque se desconoce la asociación real entre las 2 enfermedades. Pretendemos conocer la prevalencia del SAHS en enfermos diagnosticados de DS. Pacientes y método. Entre junio de 2002 y diciembre de 2004 se ha estudiado a 38 pacientes consecutivos diagnosticados de DS mediante registro Holter de 24 h. Todos fueron interrogados acerca de si presentaban síntomas relacionados con SAHS y se les hizo una polisomnografía respiratoria con un equipo validado. Resultados. La edad media de los 38 pacientes fue de 67 ± 10 años, el 68% era varón y el 58%, hipertenso. En el Holter la frecuencia máxima fue de 87 ± 6 lat/min, la mínima de 35 ± 3 lat/min y la media de 48 ± 3 lat/min. El 63% de los pacientes requirió marcapasos por DS sintomática. El 39% tenía somnolencia diurna excesiva (escala de Epworth [ESS] > 9). La polisomnografía demostró que sólo un 13% tenía un índice de apnea-hipopnea/h (IAH) normal y que el 31,6% (intervalo de confianza del 95%, 16,8-46,4) tenía un SAHS (IAH > 10 y ESS > 9). Conclusiones. Considerando que la prevalencia del SAHS en la población general es de alrededor del 3%, los resultados de nuestro estudio muestran que el SAHS es 10 veces más frecuente en pacientes con DS que en la población general, lo que indica una asociación entre las 2 enfermedades

Introduction and objectives. Sleep apnea-hypopnea syndrome (SAHS) has been associated with different cardiovascular diseases. It may even be implicated in the pathophysiology of sick sinus syndrome (SSS). However, the precise relationship between the two syndromes is still unknown. We investigated the prevalence of SAHS in patients diagnosed with SSS. Patients and method. Between June 2002 and December 2004, 38 consecutive patients who were diagnosed with SSS by 24-hour Holter monitoring were studied prospectively in our institution. All patients were asked about symptoms of SAHS, and underwent polysomnography out of hospital using a validated monitor. Results. The patients' mean age was 67 (10) years, 68% were male, and 58% were hypertensive. Holter monitoring demonstrated a maximum heart rate of 87 (6) beats/min, a minimum of 35 (3) beats/min, and a mean of 48 (3) beats/min. Some 24 (63%) patients required pacemaker implantation because of symptomatic SSS. Overall, 39% of patients had symptoms suggestive of SAHS (i.e., an Epworth index or EI>9). Polysomnography showed that only 13% of patients had a normal apnea-hypopnea index (AHI) and that 31.6% (95% CI, 16.8%-46.4%) had SAHS (i.e., AIH>10 and EI>9). Conclusions. Given that the prevalence of SAHS in the general population is around 3%, our results indicate that it is ten-fold higher in patients with SSS than in the general population. This observation indicates that there may be a relationship between the two syndromes

High oxidative stress in patients with stable coronary heart disease.

Oxidized low density lipoprotein (oxLDL) plays a pivotal role in the development of atherosclerosis. The aim of the study was to investigate the relationship between oxLDL and other oxidative stress biomarkers with stable coronary heart disease (CHD). We compared the degree of oxidative stress in patients with CHD and sex-matched healthy control subjects in a case-control study. The study included 64 male subjects: 32 patients with stable CHD and 32 normal control subjects. Levels of circulating oxLDL were measured by a monoclonal antibody 4E6-based competition ELISA. Comparison of oxidative stress marker levels between cases and controls, adjusted for age, revealed significantly higher plasma oxLDL levels (63.32+/-25.49 vs. 37.73+/-20.58 U/l, P=0.001), lower serum levels of autoantibodies against oxLDL (341.53+/-350.46 vs. 796.45+/-1034.2 mU/ml, P=0.021), higher activities of the antioxidant enzymes superoxide dismutase in erythrocytes (951+/-70.2 vs. 771.6+/-191.2 U/g, P=0.032) and glutathione peroxidase in whole blood (GSH-Px: 10714.4+/-3705.4 vs. 5512.2+/-1498.1 U/l, P<0.001). The risk of having CHD was 20.6-fold greater (95% CI, 1.86-228.44, P=0.014) in the highest tertile of the oxLDL distribution than in the lowest, determined by logistic regression analysis on the combined study population after adjustment for age and other potential confounding factors. When the risk associated with GSH-Px levels was calculated, the odds ratio was 305.3 (95% CI, 5.07-18369.95, P=0.006) in the highest tertile compared with the lowest. Our results showed that an oxidative stress occurs in patients with CHD despite being clinically stable and under medical treatment. The combination of oxLDL levels and GSH-Px activity may be useful for the identification of patients with stable CHD.