Left atrial functions in long term after catheter ablation of premature ventricular complexes.

OBJECTIVE: Premature ventricular complex (PVC) ablation has been shown to improve left ventricle (LV) diastolic function and left atrial (LA) reverse modeling, especially in the short term. In the present study, PVC ablation via radiofrequency catheter (RFCA) was evaluated with respect to its long-term effects on LA size and dynamic functions. PATIENTS AND METHODS: A total of 71 patients (age 43.49±12.8 years, 37 men [52%]) with high-burden (21% mean burden) PVCs who were treated with RFCA were included in this retrospective study. The effects of RFCA on three characteristics - LV systolic functions, LV diastolic dysfunctions and mechanical effects pertaining to the LA - were examined by echocardiography at baseline and at 3 months and 18 months after the procedure. RESULTS: Advancement in LV ejection fraction (LVEF) was seen on long-term follow-up (LVEF baseline 53.01; 3rd month 54.55; 18th month 58.02; p<0.001). LA function gradually improved after RFCA. The LA volume index was significantly decreased after RFCA (baseline 18.15±2.89; 3 months 17.11±2.71; 18 months 16.67±2.61; p<0.001). The LA passive emptying fraction was still increasing over long-term follow-up (baseline 33.33; 3rd month 37.11; 18th month 40.91; p<0.001). CONCLUSIONS: In the present study, in patients with or without apparent cardiomyopathy, RFCA was shown to successfully eliminate PVCs and improve LA functions in the long term.

A novel intermediate coronary artery stenosis severity method: Fluoroscopy-Assisted Measurement of Coronary Volume Ratio (The FLAME FFR Trial).

OBJECTIVE: The fluoroscopy-assisted coronary volume measurement (FLASH) algorithm, based on contrast passage time and vessel size, is a simple and non-invasive method of assessing coronary blood volume. The present study evaluated the diagnostic performance of FLASH flow ratio-derived fractional flow reserve (FFRFLAME) compared to wire-based FFR (FFRWB). PATIENTS AND METHODS: FFRFLAME was defined as the ratio of FLASH at baseline to maximal hyperemia. Forty-eight patients with one intermediate coronary lesion (30-70% by angiographic visual estimation) were enrolled in this cross-sectional study. FFRFLAME and FFRWB measurements were collected in each patient. Intravenous administration of adenosine was used to achieve maximal hyperemia. The Pearson correlation coefficient and receiver operating characteristic analysis were performed to determine the predictive accuracy of FFRFLAME. RESULTS: The average age of the patients was 58 years, and 43% (21 of 48) were female. The predominant vessel assessed was the left anterior descending artery system (87.5%). The mean FFRWB was 0.91 ± 0.05 at baseline and 0.83 ± 0.07 at the hyperaemic level, with 27% (13 of 48) of patients having an FFRWB of ≤0.80. For each patient, the mean FFRFLAME was 0.668 ± 0.17. The mean FFRFLAME was 0.85 ± 0.16 for patients having an FFRWB of ≤0.80. A strong relationship existed between FFRFLAME and FFRWB (Pearson's r = - 0.765 p<0.001). The optimal cutoff value of the functional significance of coronary artery stenosis for FFRFLAME was determined to be > 0.84 (AUC: 0.899, 84% sensitivity and 97% specificity) when the FFRWB cutoff value for significant lesions was ≤ 0.80. CONCLUSIONS: FFRFLAME, applied to coronary angiography without the need for an invasive pressure wire, can be a beneficial index for appropriate lesion selection in coronary artery diseases.

Evaluation of arterial stiffness and cardiac function in patients with vascular erectile dysfunction: acute effects of phosphodiesterase-5 inhibitor tadalafil.

This study aimed to detect endothelial dysfunction in erectile dysfunction (ED) patients free from cardiovascular diseases or atherosclerotic risk factors and to evaluate acute effects of phosphodiesterase-5 inhibitor tadalafil on endothelial dysfunction and cardiac function. Thirty ED patients and 20 healthy male subjects (mean ages: 48.7±11.7 and 48.3±8.7 years, respectively) were enrolled. Endothelium functions were assessed by applanation tonometry. Aortic stiffness and cardiac function were evaluated by transthoracic echocardiography. Pulse pressure was greater in the ED group (P<0.05), whereas aortic strain and aortic distensibility were significantly lower (P<0.001). Treatment with tadalafil reduced pulse pressure (P=0.0179), systolic blood pressure (P=0.001) and diastolic blood pressure (P=0.054) and increased aortic distensibility (P=0.001) and aortic strain (P=0.003) in the ED group. Tadalafil administration also increased large artery and small artery elasticity indices that were reduced in the ED group at baseline (P=0.02 and 0.003, respectively). Systemic vascular disease and compromised left ventricular diastolic function (LVDF) were present in ED patients with no known atherosclerotic risk factors and cardiac diseases. Tadalafil positively affected arterial stiffness and LVDF.

Modest correlation between serum neopterin levels and Gensini scores in a cohort of patients undergoing coronary angiography.

OBJECTIVE: We initially tried to study the possible correlation between the severity of coronary artery disease (CAD) and serum neopterin levels in stable coronary artery disease patients. Also we tried to investigate the neopterin as an indicator for the extent of CAD using the Gensini score. METHODS: A total of 40 patients with stable angina pectoris who are chosen for coronary angiography were selected for the study. Before the angiography procedure, blood samples were taken for the measurement of serum neopterin levels and the results of the coronary angiography were scored according to the Gensini scoring system. RESULTS: Neopterin levels were correlated with the Gensini scores [p = 0.010, ρ = 0.401] and a correlation between the age of patient population and Gensini score was also observed in the study [p = 0.016, ρ = 0.380]. CONCLUSION: By the guidance of our results, we can confidently state that there is a correlation between serum neopterin levels and the severity and extent of CAD in stable coronary artery disease patients.

Budesonide administered using chlorofluorocarbon and hydrofluoroalkane pressurized metered-dose inhalers: pharmacokinetics, pharmacodynamics and clinical equivalence.

OBJECTIVE: The traditional chlorofluorocarbon (CFC) propellants used in pressurized metered-dose inhalers (pMDIs) have unacceptable environmental effects and are being replaced by alternatives such as hydrofluoroalkanes (HFAs). However, there is a need to ensure that pMDIs with these novel propellants are as effective and safe as their older counterparts. MATERIALS AND METHODS: Single-dose pharmacokinetic and multiple high-dose Phase I studies in healthy volunteers and randomized, controlled 12-week Phase III clinical trials in children, adolescents and adults with mild-to-moderate asthma have been performed to compare the efficacy and safety of HFA-based budesonide inhaler therapy with the traditional CFC-based pMDI. RESULTS: The pharmacokinetic study in 40 persons showed comparable characteristics of CFC and HFApMDIs, with good dose-proportionality, at doses of 400, 800 and 1,600 microg. The high-dosage (1,600 microg/day) study in 48 subjects showed both inhaler types to be similar in terms of effects on hypothalamic-pituitary-adrenal axis function over 4 weeks. The pediatric clinical study involved 159 children and showed noninferiority of the HFA pMDI in terms of 12-week change in forced expiratory volume in 1 sec, other spirometric parameters and symptomatic measures. The adolescent/adult study in 321 subjects also showed similarity between the two formulations, in terms of 12-week primary endpoint (changes in morning peak expiratory flow rates) and other lung function and symptom measures. Both formulations were well-tolerated, with no safety issues being identified for the novel HFA inhaler in any study. CONCLUSION: Budesonide HFA pMDI is pharmacokinetically and clinically comparable to the traditional CFC-based inhaler, with similar safety profile.

Clinical comparability between the CFC and HFA budesonide pressurised metered-dose inhalers in paediatric patients with asthma: a randomised controlled trial.

OBJECTIVE: To evaluate the efficacy and tolerability of a novel hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) formulation of budesonide (Pulmicort) versus the conventional chlorofluorocarbon (CFC) pMDI formulation in paediatric patients with asthma. METHODS: This was a Phase III, multicentre, 12-week, double-blind, randomised, parallel-group study involving children (6-12 years of age) with mild to moderate asthma. Patients received either budesonide HFA pMDI or budesonide CFC pMDI 200 mug twice daily, with or without a spacer (NebuChamber/Nebunette). Primary efficacy endpoint: mean percentage change in forced expiratory volume in 1 second (FEV(1)) from baseline to week 12. Secondary efficacy endpoints included changes in FEV(1) per cent of predicted normal, forced vital capacity, morning and evening peak expiratory flow rate, asthma symptoms and use of rescue medication. RESULTS: A total of 159 patients received treatment (HFA 77, CFC 82). For mean percentage change in FEV(1) from baseline to week 12, the difference between the treatments (CFC pMDI - HFA pMDI) was -3.1% (95% confidence interval [CI] -8.0% to 1.8%) for the full analysis set and was not affected by spacer use. The upper CI was < 10% (the predefined non-inferiority margin), so non-inferiority was demonstrated. Improvements in the secondary efficacy endpoints with both budesonide formulations were not significantly different. In both groups there were similar numbers of adverse events and no evidence of oral candidiasis at week 12. CONCLUSIONS: Treatment with budesonide HFA pMDI is effective and well tolerated in children with asthma and is clinically comparable to budesonide CFC pMDI.

Clinical correlation with changing radiographic appearance during partial liquid ventilation.

STUDY OBJECTIVES: To evaluate the chest radiographic filling pattern associated with partial liquid ventilation (PLV) with the perfluorochemical perflubron (LiquiVent; Alliance Pharmaceutical Corp; San Diego CA) as a function of dose and timing. DESIGN: Post hoc review of chest radiographs by three independent observers with correlation to clinical variables. SETTING: Phase II randomized, uncontrolled, prospective, multicenter clinical trial. PATIENTS: Sixteen adult patients with diffuse bilateral infiltrates consistent with acute lung injury and a PaO(2)/fraction of inspired oxygen (FIO(2)) ratio < 300 with positive end-expiratory pressure of 13 cm H(2)O and FIO(2) > or = 0.5. INTERVENTIONS: All patients were treated with either a 10-mL/kg or 20-mL/kg loading dose of perflubron followed by maintenance dosing at 3-h intervals to protocol-determined levels. RESULTS: There was a significant relationship between inhomogeneous radiographic filling during the first 48 h of treatment and the use of the lower loading dose of perflubron. Inhomogeneous radiographic filling (in 5 patients) was associated with a lower high-dose/FIO(2) ratio at 24 h compared with the remaining patients. These differences resolved by 48 h. There were no other statistically significant correlations identified. CONCLUSIONS: The radiographic appearance of PLV with perflubron appears to depend on the dose administered. Lower doses can be associated with both inhomogeneous radiographic filling and a transient deterioration in oxygenation during the first 24 to 48 h of treatment.

Risk factors for early-onset, ventilator-associated pneumonia in critical care patients: selected multiresistant versus nonresistant bacteria.

BACKGROUND: Ventilator-associated pneumonia is the leading nosocomial infection in critically ill patients. The frequency of ventilator-associated pneumonia caused by multidrug-resistant bacteria has increased in recent years, and these pathogens cause most of the deaths attributable to pneumonia. The authors, therefore, evaluated factors associated with selected multidrug-resistant ventilator-associated pneumonia in critical care patients. METHODS: The authors prospectively recorded potential risk factors at the time of intensive care unit admission. An endotracheal aspirate was obtained in all patients who met clinical criteria for pneumonia. Patients were considered to have ventilator-associated pneumonia only when they met the clinical criteria and aspirate culture was positive for bacteria 48 h or more after initiation of mechanical ventilation. Pediatric patients were excluded. Adult patients with ventilator-associated pneumonia were first grouped as "early-onset" (< 5 days) and "late-onset," determined by episodes of ventilator-associated pneumonia, and then, assigned to four groups based on the bacteria cultured from their tracheal aspirates: Pseudomonas aeruginosa, Acinetobacter baumanii, methicillin-resistant staphylococci, and all others. The first three bacteria were considered to be multidrug resistant, whereas the others were considered to be antibiotic susceptible. Potential risk factors were evaluated with use of univariate statistics and multivariate regression. RESULTS: Among 486 consecutive patients admitted during the study, 260 adults underwent mechanical ventilation for more than 48 h. Eighty-one patients (31%) experienced 99 episodes of ventilator-associated pneumonia, including Pseudomonas(33 episodes), methicillin-resistant staphylococci (17 episodes), Acinetobacter(9 episodes), and nonresistant bacteria (40 episodes). Sixty-six of these episodes were early onset and 33 episodes were late onset. Logistic regression analysis identified three factors significantly associated with early-onset ventilator-associated pneumonia caused by any one of the multidrug-resistant bacterial strains: emergency intubation (odds ratio, 6.4; 95% confidence interval, 2.0-20.2), aspiration (odds ratio, 12.7; 95% confidence interval, 2.4-64.6), and Glasgow coma score of 9 or less (odds ratio, 3.9; 95% confidence interval, 1.3-11.3). A. baumanii-related pneumonia cases were found to be significantly associated with two of these factors: aspiration (odds ratio, 14.2; 95% confidence interval, 1.5-133.8) and Glasgow coma score (odds ratio, 6.0; 95% confidence interval, 1.1-32.6). CONCLUSIONS: The authors recommend that patients undergoing emergency intubation or aspiration or who have a Glasgow coma score of 9 or less be monitored especially closely for early-onset multidrug-resistant pneumonia. The occurrence of aspiration and a Glasgow coma score of 9 or less are especially associated with pneumonia caused by A. baumanii.

Comparison of pressure- and flow-triggered pressure-support ventilation on weaning parameters in patients recovering from acute respiratory failure.

OBJECTIVE: To compare the effects of pressure- and flow-triggered pressure-support ventilation on weaning parameters during recovery from acute respiratory failure. DESIGN: Prospective, randomized, clinical trial. SETTING: Intensive care unit in a university hospital. PATIENTS: Sixteen orotracheally intubated adult patients recovering from acute respiratory failure of various etiologies, without chronic obstructive pulmonary disease. INTERVENTIONS: Randomized application of pressure- and flow-triggered pressure-support ventilation at 100% and 75% ventilatory support levels in each triggering system. A total of four conditions were applied for 30 mins each in all patients. MEASUREMENTS AND MAIN RESULTS: Ventilatory, respiratory, and hemodynamic data were measured. For the measurement of weaning parameters, pressure and volume signals were directed to a computerized respiratory monitor by means of an esophageal probe and a flow sensor between the "Y" piece of the ventilatory circuit and the endotracheal tube. During both pressure-triggered (trigger sensitivity of -1 cm H2O) and flow-triggered (trigger sensitivity of 0.7 to 2.0 L/min) pressure-support ventilation with a ventilator, peak airway pressures were applied so as to decrease the work of breathing performed by the patient to zero (full ventilatory support). Partial ventilatory support was applied at 75% of the peak airway pressures achieved during full ventilatory support with each triggering system. A total of four experimental conditions were evaluated at identical FiO2 and positive and-expiratory pressure levels during pressure-support ventilation in each patient. Total ventilation volumes, arterial blood gas data, and hemodynamics did not differ among the four experimental conditions. During partial ventilatory support, the work of breathing, rapid shallow breathing index, and esophageal pressure increased significantly with both triggering systems when compared with data obtained at full ventilatory support. The mean data for the weaning parameters during the condition of partial ventilatory support were comparable between pressure- and flow-triggered pressure-support ventilation (i.e., 0.38 +/- 0.24 vs. 0.42 +/- 0.26 joule/L for work of breathing, 2.6 +/- 1.6 vs. 3.3 +/- 1.7 cm H2O for tracheal occlusion pressure, and 40.2 +/- 12.9 vs. 50.4 +/- 18.3 breaths/min/L for rapid shallow breathing index, respectively). CONCLUSIONS: The application of either a pressure- or flow-triggered system during pressure-support ventilation with the ventilator did not significantly affect short-term changes in gas exchange, respiratory mechanics, and inspiratory workload in patients recovering from acute respiratory failure of various etiologies without chronic obstructive pulmonary disease.

Evaluation of lung function after intratracheal perfluorocarbon administration in healthy animals.

OBJECTIVES: To investigate the effects of partial liquid ventilation (i.e., mechanical ventilation in combination with intratracheal administration of perfluorocarbon) on lung function, with particular attention to the integrity of the alveolocapillary membrane in healthy adult animals. DESIGN: Prospective, randomized, controlled study. SETTING: Laboratory at the Department of Experimental Anesthesiology, Erasmus University Rotterdam. SUBJECTS: Ten adult male New Zealand rabbits. INTERVENTIONS: Five rabbits were intratracheally treated with 12 mL/kg of perfluorocarbon while conventional mechanical ventilation (volume-controlled, tidal volume of 12 mL/kg, respiratory rate of 30 breaths/min, inspiration/expiration ratio of 1:2, positive end-expiratory pressure of 2 cm H2O, and an FIO2 of 1.0) was applied for 3 hrs. To assess the permeability of the alveolocapillary membrane, pulmonary clearance of inhaled technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) measurements were performed at 3 hrs and compared with data from the control group (n = 5) treated with mechanical ventilation only, using the same ventilatory parameters. MEASUREMENTS AND MAIN RESULTS: Pulmonary gas exchange and lung mechanical parameters were measured in both groups at 30-min intervals. Mean values for PaO2 in the perfluorocarbon group, although at adequate levels, were less than those values of the control group during the 3-hr study period (370 +/- 44 vs. 503 +/- 44 torr at 3 hrs [49.3 +/- 5.9 vs. 67.1 +/- 5.9 kPa]). Peak and mean airway pressures were higher in the perfluorocarbon group (ranging from 1.9 to 3.4 cm H2O and 0.7 to 1.3 cm H2O, respectively) compared with the control group, while end-inspiratory airway pressure was similar in both groups. The half-life of 99mTc-DTPA was 83.7 +/- 24.5 mins in the control group, which was significantly longer (p < .01) than in the perfluorocarbon group (49.8 +/- 6.1 mins). CONCLUSIONS: These findings suggest that partial liquid ventilation with perfluorocarbons lowers pulmonary gas exchange in healthy animals, and the increased pulmonary clearance of 99mTc-DTPA after 3 hrs of this type of ventilatory support may reflect minimal reversible changes in the lung surfactant system.

Respiratory and haemodynamic effects of conventional volume controlled PEEP ventilation, pressure regulated volume controlled ventilation and low frequency positive pressure ventilation with extracorporeal carbon dioxide removal in pigs with acute ARDS.

The purpose of this study was to evaluate whether any benefit of low frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV-ECCO2R) existed over either volume controlled ventilation (VCV) with measured best-PEEP or pressure regulated volume controlled ventilation (PRVCV) with an inspiration/expiration (I/E) ratio of 4:1, with respect to arterial oxygenation, lung mechanics and haemodynamics, in acute respiratory failure. Fifteen adult pigs were used for the study. Respiratory failure was induced by surfactant depletion by repeated lung lavage. The different therapeutic approaches were applied randomly to each pig for 1 h. Measurements of gas exchange, airway pressures and haemodynamics were performed during ventilatory and haemodynamic steady state. Paco2 was kept constant in all modes. At almost similar total-PEEP, Pao2 values were significantly higher with LFPPV-ECCO2R compared to VCV with best-PEEP. Peak inspiratory pressure (PIP) and intrapulmonary pressure amplitude defined as the difference between PIP and total-PEEP were significantly lower with PRVCV and LFPPV-ECCO2R compared to VCV with best-PEEP. There was no significant difference between the modes concerning cardiocirculatory parameters. PRVCV with I/E ratio of 4:1 and LFPPV-ECCO2R proved to be better modes to achieve better gas exchange and lower PIP at lower intrapulmonary pressure amplitudes. It is concluded that PRVCV is an adequate form of treatment under these experimental conditions imitating acute respiratory failure, without necessitating other invasive measures.