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Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n=126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV1) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n=125, 69 years) showed milder airflow limitation (FEV1 63% predicted); and group 3 (n=91, 67 years) combined a similarly milder airflow limitation (FEV1 58% predicted) with a high proportion of obesity, cardiovascular disorders, diabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p<0.001) and higher all-cause mortality (HR 2.36, p=0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p=0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated: ‘severe respiratory COPD’, ‘moderate respiratory COPD’, and ‘systemic COPD’.

Ischaemic postconditioning revisited: lack of effects on infarct size following primary percutaneous coronary intervention

AIMS To assess the short- and long-term effects of postconditioning (p-cond) on infarct size, extent of myocardial salvage, and left ventricular ejection fraction (LVEF) in a series of patients presenting with evolving ST-elevation myocardial infarction (STEMI). Previous studies have shown that p-cond during primary percutaneous coronary intervention (PCI) confers protection against ischaemia-reperfusion injury and thus might reduce myocardial infarct size. METHODS AND RESULTS Seventy-nine patients undergoing PCI for a first STEMI with TIMI grade flow 0-1 and no collaterals were randomized to p-cond (n= 39) or controls (n= 40). Postconditioning was performed by applying four consecutive cycles of 1 min balloon inflation, each followed by 1 min deflation. Infarct size, myocardial salvage, and LVEF were assessed by cardiac-MRI 1 week and 6 months after MI. Postconditioning was associated with lower myocardial salvage (4.1 ± 7.2 vs. 9.1 ± 5.8% in controls; P= 0.004) and lower myocardial salvage index (18.9 ± 27.4 vs. 30.9 ± 20.5% in controls; P= 0.038). No significant differences in infarct size and LVEF were found between the groups at 1 week and 6 months after MI. CONCLUSION This randomized study suggests that p-cond during primary PCI does not reduce infarct size or improve myocardial function recovery at both short- and long-term follow-up and might have a potential harmful effect.

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.

Electrocardiographic Optimization of Interventricular Delay in Cardiac Resynchronization Therapy: A Simple Method to Optimize the Device

Introduction: Echocardiography is widely used to optimize CRT programming, but it is time‐consuming. This study aimed to correlate the optimal interventricular pacing (V‐V) interval obtained by echo with the optimal V‐V interval obtained by a simpler method based on the surface ECG.

Fate of left atrial function as determined by real-time three-dimensional echocardiography study after radiofrequency catheter ablation for the treatment of atrial fibrillation.

Radiofrequency catheter ablation has been demonstrated to be effective in the treatment of patients with atrial fibrillation. However, its impact on left atrial (LA) function has not been widely studied. The purpose of the present study was to evaluate the impact of radiofrequency catheter ablation on LA function in patients with atrial fibrillation. Thirty-eight patients with symptomatic drug-refractory atrial fibrillation were treated with circumferential pulmonary vein ablation (CPVA). LA volumes and function were assessed with real-time 3-dimensional echocardiography before and 6 months after the procedure. The effectiveness of CPVA was evaluated at 6-month follow-up. Recurrence of the arrhythmia was defined as any documented (clinically or on 24-hour Holter electrocardiography) atrial tachyarrhythmia lasting>30 seconds after the first 12 weeks after the procedure. CPVA induced a reduction of maximum LA volume (from 55+/-15 to 48+/-16 ml, p<0.001), without impairment in LA function, measured as the active emptying percentage of total volume (32+/-29% vs 39+/-33%, p=NS). At follow-up, 21 patients (61.8%) had no recurrences. Maximum LA volumes were significantly larger in patients who presented with recurrences compared with those who did not (64+/-18 vs 50+/-11 ml, p=0.01). In conclusion, CPVA induces a reduction in LA volume without a deleterious impact on function, and, of importance, real-time 3-dimensional echocardiography is a useful noninvasive imaging tool to follow up LA remodeling and function in these patients.

Echocardiographic abnormalities in patients with COPD at their first hospital admission

Cardiovascular disease accounts for significant morbidity and mortality in chronic obstructive pulmonary disease (COPD). Its prevalence and mechanisms of association have not been elucidated. The study aimed to assess the prevalence of echocardiographic abnormalities and potential risk factors in patients with COPD at their first exacerbation requiring hospital admission. Transthoracic echocardiography was prospectively performed in 342 patients (forced expiratory volume in 1 s 52±16% predicted) 3 months after discharge. Significant cardiac alterations were present in 64% of patients; 27% left- and 48% right-heart disorders. The most common were right ventricle enlargement (30%) and pulmonary hypertension (19%). Left ventricle enlargement was present in 6%, left ventricle systolic dysfunction in 13%, left ventricle diastolic impairment in 12% and left atrial dilatation in 29%. Echocardiographic abnormalities were unrelated to COPD severity and were more frequent in patients with self-reported cardiac disease. They were also observed in 63% of patients with no known cardiac disease or cardiovascular risk factors other than smoking. We conclude that cardiac abnormalities are highly prevalent in COPD patients at the time of their first severe exacerbation, even in the absence of established cardiac disease or cardiovascular risk factors. Considering the prognostic and therapeutic implications of cardiac comorbidity, echocardiography should be considered in the assessment of patients with clinically significant COPD.

Guías de práctica clínica de la Sociedad Española de Cardiología en valvulopatías

Las enfermedades de las valvulas cardiacas, que siguen siendo una causa importante de morbimortalidad en todo el mundo, han sufrido cambios radicales desde hace 40 anos, en que se implantaron las primeras protesis. Estos cambios han sido propiciados por los avances cientifico-tecnologicos, pero tambien por la mejoria en las condiciones de vida de los paises desarrollados. La disponibilidad de la penicilina para tratar las faringoamigdalitis estreptococicas y un menor hacinamiento que el existente antano han hecho de la fiebre reumatica una rara entidad en los paises desarrollados. Como contrapartida, han aparecido a lo largo de los anos otras formas de afectacion valvular. La etiologia de algunas de estas valvulopatias (p. ej., la valvula mitral mixomatosa) sigue siendo desconocida; otras, como la estenosis valvular aortica calcificada de tipo senil, parecen ser el tributo a pagar por el alargamiento en la expectativa de vida. Por lo que respecta al diagnostico, la ecocardiografia se ha erigido en una poderosisima herramienta para visualizar los cambios anatomicos de las valvulas, interpretar los complejos trastornos hemodinamicos y valorar la repercusion sobre el ventriculo izquierdo. Ademas, la iteracion de estas exploraciones incruentas ha permitido conocer mucho mejor la historia natural de las valvulopatias leves o moderadas y precisar mas adecuadamente el momento idoneo de la intervencion quirurgica, sin esperar, en muchos casos, la aparicion de sintomatologia avanzada. Esto ha sido posible tambien por los grandes avances de la cirugia, que se pueden resumir en: a) la mejora de las tecnicas de circulacion extracorporea y de la proteccion miocardica; b) el perfeccionamiento de los sustitutos valvulares, tanto mecanicos como biologicos; c) la introduccion de tecnicas imaginativas para reparar las lesiones de la valvula mitral, y d) la utilizacion del eco transesofagico para valorar intraoperatoriamente la calidad de la reparacion valvular. Paralelamente, la dilatacion con cateter-balon de la valvula mitral estenotica ha surgido como alternativa a la comisurotomia mitral quirurgica. Todos estos cambios, y otros muchos que no es posible referir en este resumen, hacen oportuno que revisemos el manejo actual del paciente portador de una valvulopatia.

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.

Usefulness of transoesophageal echocardiography before circumferential pulmonary vein ablation in patients with atrial fibrillation: is it really mandatory?

AIMS Transoesophageal echocardiography (TEE) is recommended prior to circumferential pulmonary vein ablation (CPVA) in patients with atrial fibrillation (AF) to identify left atrial (LA) or left atrial appendage (LAA) wall thrombi. It is not clear whether all patients undergoing CPVA should receive pre-procedural TEE. We wanted to assess the incidence of LA thrombus in these patients and to identify factors associated with its presence. METHODS AND RESULTS Consecutive patients referred for CPVA from 2004 to 2009 underwent TEE within 48 h prior to the procedure. Of 408 patients included in the study, 6 patients (1.47%) had LA thrombi, persistent AF, and LA dilation. Compared with patients without thrombus, these six patients had larger LA diameter (P = 0.0001) and more frequently were women (P = 0.002), had persistent AF (P = 0.04), and had underlying structural cardiac disease (P = 0.014). The likelihood of presenting LA thrombus increased with the number of these four risk factors present (P < 0.001). None of the patients with paroxysmal AF and without LA dilation had LA thrombus. A cut-off value of 48.5 mm LA diameter yielded 83% sensitivity, 92% specificity, and a 10.1 likelihood ratio to predict LA thrombus appearance. CONCLUSION The incidence of LA thrombus prior to CPVA is low. Persistent AF, female sex, structural cardiopathy, and LA dilation were associated with the presence of LA thrombus. Our data suggest that the use of TEE prior to CPVA to detect LA thrombi might not be needed in patients with paroxysmal AF and no LA dilation or structural cardiopathy.