Deceleration and Acceleration Capacities in Risk Stratification for Arrhythmias in Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk for both supraventricular and ventricular arrhythmias. Autonomic dysregulation may be responsible for the development of arrhythmias in these patients, and its analysis could be useful for identifying those at high risk for arrhythmias. STUDY QUESTION: Our purpose is to analyze the role of acceleration capacity (AC) and deceleration capacity (DC), novel markers of the autonomic balance, as potential arrhythmic risk predictors in patients with COPD. STUDY DESIGN: We prospectively included 47 patients diagnosed with COPD, and a control group of 64 age-matched subjects without COPD. AC and DC values were obtained using 24-hour Holter monitoring. The arrhythmias were isolated premature atrial complexes, supraventricular tachycardias, isolated premature ventricular beats (PVC), and combined ventricular arrhythmias consisting in ventricular tachycardias or more than 10 PVC per hour. RESULTS: Supraventricular arrhythmias and isolated PVC were more frequent in the COPD group. The DC was significantly lower (3.10 vs. 5.60, P < 0.0001) and AC higher (-4.60 vs. -6.60, P = 0.002) in patients with COPD. DC was identified as a predictor of arrhythmic events with an area under the curve (AUC) for premature atrial complexes >70/d of 0.72 (0.56-0.87, P = 0.013), for supraventricular tachycardias 0.76 (0.62-0.90, P = 0.002), and for combined ventricular arrhythmias 0.69 (0.54-0.82, P = 0.025). AC was predictor only for combined ventricular arrhythmias with an AUC of 0.74 (0.58-0.85, P = 0.002). CONCLUSIONS: Patients with COPD associate a significant autonomic imbalance and a higher incidence of arrhythmias. DC could be a strong predictor for supraventricular and ventricular arrhythmias in patients with COPD with no clinically apparent cardiac disease. AC could be useful alongside with DC regarding the risk for ventricular arrhythmias, but seems to have lesser value as a predictor for supraventricular arrhythmias.

Circulating Reticulocalbin 1 and Reticulocalbin 3 in Systemic Sclerosis Patients: Results of a Case Control Study.

BACKGROUND: Proteomic candidate biomarkers for systemic sclerosis (Ssc) useful for appropriate patient evaluation and follow-up were identified in mass-spectrometry studies; however, most of these biomarkers were not evaluated and confirmed on independent patient samples. Up-regulation of reticulocalbin 1 (RCN1) and reticulocalbin 3 (RCN3) in the dermal fibroblast secretome originating from Ssc patients was previously described. The aim of the study was to evaluate circulating RCN1 and RCN3 as candidate biomarkers for Ssc clinical expression. METHODS: 40 consecutive Ssc patients and 20 gender and age matched controls were included. Serum RCN1 and RCN3 was evaluated using commercial ELISA kits. RESULTS: Serum RCN1 and RCN3 were not statistically significant different between Ssc patients and healthy controls. Serum RCN1 and RCN3 were correlated in both Ssc and healthy control groups (p < 0.001). Serum RCN1 was positively correlated with Ssc disease activity score (EUSTAR, p = 0.02) and remained associated with EUSTAR after adjusting for disease duration in multivariate analysis. 6 Ssc patients (15%) had elevated RCN1 values compared to reference values obtained from healthy control samples. These patients had higher prevalence of digital ulcers, higher disease activity scores, and tended to have esophageal hypomotility, calcinosis, telangiectasia, and diffuse Ssc subtype. CONCLUSIONS: RCN1 and RCN3 expression was not statistically significantly different to healthy controls. However, RCN1 was associated with disease activity score and could be used as a stratification biomarker for Ssc patients, as patients with high RCN1 shared a particular disease pattern.

Role of signal-averaged electrocardiography and ventricular late potentials in patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) have an increased risk for cardiac arrhythmias. Ventricular late potentials (VLP) on signal-averaged electrocardiography (SAECG) are associated with an increased risk for malignant ventricular arrhythmias. Our aim is to investigate the modifications of SAECG parameters and the presence of VLP as possible indicators of proarrhythmic substrate in patients with COPD. We prospectively enrolled 41 consecutive patients in the COPD group and 63 patients without any history of pulmonary disease, matched for age and hypertension history, in the control group. Pulmonary function tests, arterial blood gases, echocardiography, 24-hour Holter monitoring and SAECG were performed. We measured total filtered QRS duration (QRSf), duration of high frequency, low-amplitude signals < 40 V (HFLA40), and root mean square voltage in the last 40 ms (RMS40). VLP were considered if at least two of these parameters were abnormal. Results. We did not register any significant differences in QRSf, HFLA40 or RMS40 between the two groups. In the COPD group there was a non-significant higher percentage of patients with VLP in comparison with the control group. In the COPD patients we registered a significantly higher number of isolated premature ventricular beats and of combined complex ventricular arrhythmias, consisting of polymorphic PVC, couplets, triplets or nonsustained ventricular tachycardias. None of these arrhythmic parameters correlated with SAECG variables or with the presence of VLP. Conclusion. In COPD patients parameters measured on signal-averaged electrocardiography and ventricular late potentials analysis have little value in risk stratification for ventricular arrhythmias.

P Wave Signal-Averaged Electrocardiography in Patients with Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with higher incidence of supraventricular arrhythmias. Atrial late potentials (ALP) detected by P-wave signal-averaged electrocardiography (SAECG) could be useful in detecting the patients at risk for supraventricular arrhythmias. Our objective was to assess the role of P-wave SAECG and ALP detection for arrhythmic risk evaluation of the patients with exacerbated COPD. METHODS: We prospectively included 45 patients with exacerbation of COPD and 58 age- matched patients with no history of pulmonary disease in a control group. We performed pulmonary function tests, arterial blood gases, echocardiography, 24-hour Holter monitoring and P-wave SAECG. We measured filtered P-wave duration (FPD), the root mean square (RMS) voltages in the last 40, 30 and 20 ms of the filtered P-wave (RMS 40, RMS 30 and RMS 20), the root mean square voltage of the filtered P-wave potentials (RMS-p), and the integral of the potentials during the filtered P-wave (Integral-p). ALP was defined as FPD > 132 ms and RMS 20 < 2.3 µV. RESULTS: Isolated atrial premature beats (APB) and supraventricular tachycardias (SVT) were more frequent in the COPD group. There were no significant differences between groups regarding the P wave SAECG parameters. In the COPD group none of the supraventricular arrhythmias was correlated with ALP or any P-wave SAECG parameters. CONCLUSIONS: The patients with acute exacerbation of COPD but no apparent cardiac disease have a higher incidence of supraventricular arrhythmias. P-wave SAECG analysis and ALP detection have little value in the arrhythmic risk evaluation of these patients.

Body composition in patients with chronic obstructive pulmonary disease.

OBJECTIVES: Body composition assessment in chronic obstructive pulmonary disease (COPD) is important, as weight loss and muscular wasting are responsible for low exercise capacity in these patients, and low body mass index (BMI) and fat free mass index (FFMI) are important prognostic factors. Our study aims were: (a) to describe body composition in COPD patients referred to a pulmonary rehabilitation center in Bucharest; (b) to examine the relationships between body composition and disease severity (bronchial obstruction, exercise capacity, quality of life); (c) to test if segmental wasting of lower limbs muscle mass (measured by segmental body composition analysis) correlates with decreased exercise capacity. MATERIAL AND METHODS: We studied 36 consecutive COPD patients referred to our clinic for pulmonary rehabilitation. Patients performed pulmonary function tests, six minutes walking test (6MWT), and health status was evaluated with COPD Assessment Test (CAT). Body composition measurements were performed by direct segmental multi-frequency bioelectrical impedance analysis (BIA). OUTCOMES: This study offers the first data on body composition of Romanian COPD patientsThe prevalence of nutritional depletion (defined by low BMI and/or low FFMI) among our COPD patients was 22.2%. Mean FFMI was significantly lower in normal or underweight patients versus overweight or obese patients. Patients with low FFMI had lower exercise capacity at the 6MWT and higher CAT scores than patients with normal FFMI.Depending on the BMI and FFMI values the patients were divided in four categories: normal, semistarvation, sarcopenia and cachexia. The group of patients with sarcopenia (low FFMI and normal BMI) had the lowest mean MIP (Maximal Inspiratory Pressure), the lowest mean 6MWD (six minutes walking distance) and the higher CAT mean scores among all groups. Exercise capacity was significantly lower in muscular depleted patients (with low skeletal muscle mass index - SSMI). MIP correlated significantly with FFMI and SMMI. No correlations were found between parameters of body composition and FEV1 or CAT. Segmental body composition assessment revealed that unbalanced upper/lower skeletal muscle mass is associated with a lower exercise capacity as measured by 6WMT. CONCLUSIONS: This study offers the first data on body composition of Romanian COPD patients. The prevalence of nutritional depletion is similar to that found in other European studies. No significant correlations were found between FFMI and severity of the disease (bronchial obstruction, distance walked, CAT score). FFMI and SSMI correlated significantly with MIP. Sarcopenic patients had the lowest mean 6MWD, the lowest mean MIP and the highest CAT mean scores. SMMI significantly correlated with 6MWD. Segmental body composition assessment of revealed that "unbalanced" patients had lower results at 6MWT. These results show that body composition evaluation is useful for the assessment of COPD patients referred to pulmonary rehabilitation and should be routinely performed.

Prevalence and Characteristics of Pulmonary Hypertension Associated with COPD - A Pilot Study in Patients Referred to a Pulmonary Rehabilitation Program Clinic.

OBJECTIVES: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmo-nary disease (COPD); its prevalence is currently unknown. The objectives of the study were: (a) to provide data on the prevalence of PH among the COPD patients referred to a pulmonary rehabilitation program; (b) to evaluate possible correlations of PH with the severity of COPD, the presence of hypoxemia and polycythemia. MATERIAL AND METHODS: We retrospectively studied 31 consecutive patients with the diagnosis of COPD hospitalised in our clinic in which echocardiography was performed. Spirometry, peripheral oxygen saturation, haematocrit, echocardiography data, history of exacerbations and cardiac comorbidities were obtained from patients records. PH was defined as systolic pulmonary arterial pressure (sPAP) greater than 35 mmHg or by the presence of right ventricle (RV) abnormalities. OUTCOMES: The prevalence of PH was 38.7%. Resting hypoxemia was significantly more frequent in the PH group than in the non PH patients (p=0.019). Other differences were not statistically significant (severity of bronchial obstruction and polycythemia, cardiac comorbidities). The impact of PH on RV was found in only 5 patients with RV enlargement; no patient had RV hypertrophy or RV systolic dysfunction. Suspected "out of proportion" PH (sPAP greater than 50 mmHg) was encountered in 2 out of 12 patients with PH. CONCLUSIONS: The prevalence of PH in patients with COPD was 38.7%. Resting hypoxemia was significantly more frequent in PH patients. As PH has an important role in the prognosis of COPD patients, it should be evaluated in as many COPD patients as possible.

Benefits of a 7-week outpatient pulmonary rehabilitation program in COPD patients.

BACKGROUND: Respiratory rehabilitation programs (RR) are essential tools in the management of COPD. AIM: We present the results of a 7-week outpatient rehabilitation program in terms of dyspnea, exercise tolerance and quality of life. MATERIAL AND METHOD: The following parameters were evaluated before and after RR: dyspnea (mMRC scale), pulmonary function (FEVI, RV- residual volume), exercise tolerance (6MWT- 6 minutes walk test, CPET - cardiopulmonary exercise test), quality of life (SGROQ questionnaire). The RR program was outpatient, hospital based (7 weeks, 3 sessions/ week) and included: exercise training, therapeutic education, and psychological support. RESULTS: 25 patients, COPD stage II-IV GOLD (mean FEVI 44.5 +/-13% predicted), mean age 60.4 +/-12 years, 7 females, average BMI 27.14+/-4 kg/m2, average RV residual volume 221.55+/-86% predicted. Mean 6MWTdistance: 407.48 +/- 84 m and mean maximum power (Pmax) obtained on CPET: 75.67+/-30 Watts. All patients were symptomatic with significant dyspnea (3.06+/-0.7 on mMRC scale) and showed a significant impairment of quality of life: SGRO score 46.23+/- 14. At the end of RR program: dyspnea decreased with 0.67points on mMRC scale (p = 0.000), 6MWT distance increased with 58.5 m (p = 0.0071), Pmax obtained during CPET increased with 11.2 W, without reaching statistical significance (p> 0.05). SGRO score decreased by 5.59 points (p = 0.02). There were no significant improvements in FEV1 and RV values (p> 0.05). CONCLUSION: In our COPD patients, the 7 week outpatient rehabilitation program was effective, leading to improvement ofsymptoms, exercise tolerance and quality of life.

[Dynamic hyperinflation -- the main mechanism of decreased exercise tolerance in patients with COPD]. / Hiperinflatia pulmonara -- mecanismul principal al scaderii tolerantei de efort a pacientilor cu BPOC.

Decreased exercise tolerance in patients with COPD is the result of involvement in variable proportion of three mechanisms: ventilatory limitation, muscle dysfunction and cardio-vascular involvement (inadequate intake of oxygen at tissue level). Ventilatory limitation is caused by the combination of increased demand and decreased ventilatory capacity Increased ventilatory demand is the result of exercise worsening of ventilation-perfusion imbalance, and decreased ventilatory capacity is the result of decreased elastic recoil and dynamic obstruction. The consequence is the expiratory flowlimitation, leading to inefficientexpiratory muscle activity and dynamic hyperinflation. Dynamic hyperinflation is a result of structural abnormalities in COPD producing mechanical disorders that limit ventilation. Dynamic hyperinflation has some beneficial effects by facilitating maximal exhalation. Negative effects ofhyperinflation are: (1) decreased tidal volume ability to grow properly at exercise, which causes mechanical ventilatorlimitation; (2) decreased functional capacity of inspiratory musles (by increasing elastic load with respiratory muscle fatigue and increase work ofbreathing); (3) exercise hypoxemia and carbon dioxide retention; (4) impairmentof cardiac function during exercise by decreasing venous return and cardiac output. Evaluation of pulmonary hyperinflation is a useful tool for better characterizing the effects of disease and for monitoring the response of therapeutic interventions on exercise tolerance of patients with COPD.

Pulmonary hypertension secondary to chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the most common cause of secondary pulmonary hypertension (PH). PH secondary to COPD is associated with a worse prognosis of the disease, a low quality of life, as well as with a higher exacerbation frequency, and consequently with an increase in the healthcare cost of COPD patients. Prevalence of PH in COPD patients is currently unknown. The most important mechanisms leading to PH are hypoxic vasoconstriction, pulmonary hyperinflation and endothelial dysfunction. PH should be suspected in COPD patients in the presence of severe dyspnoea, disproportionate from the decline in lung function, or of severe hypoxemia. Exercise induced PH is an independent predictor of the development of resting PH in patients with COPD. Echocardiography is the first screening method for PH in patients with COPD and it should be widely used, as it can also appreciate the cardiac consequences of PH, especially on the right ventricle. Given the high negative predictive value of the echocardiographic estimation of systolic pulmonary arterial pressure (sPAP) in the diagnosis of PH, the absence of a high sPAP excludes important PH and further unnecessary invasive evaluation. Right cardiac catheterization remains the "gold standard" method in assessing PH, but it is less accessible and cannot be used in routine evaluation of patients with COPD. PH secondary to COPD is usually mild, but a small proportion of patients have severe PH, with specific characteristics, worse prognosis and a specific therapeutic approach.