Birgitta Houltz

Electrocardiographic and Clinical Predictors of Torsades de Pointes Induced by Almokalant Infusion in Patients with Chronic Atrial Fibrillation or Flutter: A Prospective Study

The aim of this study was to identify predictors of torsades de pointes (TdP) in patients with atrial fibrillation (AF) or flutter exposed to the Class III antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong myocardial repolarization. One hundred patients received almokalant infusion during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the following day (infusion 2). Thirty‐two patients converted to SR. Six patients developed TdP. During AF, T wave alternans was more common prior to infusion (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of infusion 1, the TdP patients exhibited a longer QT interval (493 ± 114 vs 443 ± 54 ms [mean ± SD], P < 0.01), a larger precordial QT dispersion (50 ± 74 vs 27 ± 26 ms, P < 0.05), and a lower T wave amplitude (0.12 ± 0.22 vs 0.24 ± 0.16 mV. P < 0.01). After 30 minutes of infusion 2, they exhibited a longer QT interval (672 ± 26 vs 489 ± 74 ms, P < 0.001), a larger QT dispersion in precordial (82 ± 7 vs 54 ± 52 ms, P < 0.01) and extremity leads (163 ± 0 vs 40 ± 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P < 0.001). Risk factors for development of TdP were at baseline: female gender, ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of infusion: sequential bilateral bundle branch block, ventricular extrasystoles in bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during almokalant infusion a pronounced QT prolongation, increased QT dispersion, and marked morphological T wave changes.

A realistic validation study of a new nitrogen multiple-breath washout system

Background For reliable assessment of ventilation inhomogeneity, multiple-breath washout (MBW) systems should be realistically validated. We describe a new lung model for in vitro validation under physiological conditions and the assessment of a new nitrogen (N2)MBW system. Methods The N2MBW setup indirectly measures the N2 fraction (FN2) from main-stream carbon dioxide (CO2) and side-stream oxygen (O2) signals: FN2 = 1−FO2−FCO2−FArgon. For in vitro N2MBW, a double chamber plastic lung model was filled with water, heated to 37°C, and ventilated at various lung volumes, respiratory rates, and FCO2. In vivo N2MBW was undertaken in triplets on two occasions in 30 healthy adults. Primary N2MBW outcome was functional residual capacity (FRC). We assessed in vitro error (√[difference]2) between measured and model FRC (100–4174 mL), and error between tests of in vivo FRC, lung clearance index (LCI), and normalized phase III slope indices (Sacin and Scond). Results The model generated 145 FRCs under BTPS conditions and various breathing patterns. Mean (SD) error was 2.3 (1.7)%. In 500 to 4174 mL FRCs, 121 (98%) of FRCs were within 5%. In 100 to 400 mL FRCs, the error was better than 7%. In vivo FRC error between tests was 10.1 (8.2)%. LCI was the most reproducible ventilation inhomogeneity index. Conclusion The lung model generates lung volumes under the conditions encountered during clinical MBW testing and enables realistic validation of MBW systems. The new N2MBW system reliably measures lung volumes and delivers reproducible LCI values.

Short-term sinus rhythm predicts long-term sinus rhythm and clinical improvement after intraoperative ablation of atrial fibrillation

AIMS Our aim was to compare the long-term effects on rhythm and quality of life (QoL) after left atrial epicardial radiofrequency (RF) ablation vs. no ablation in patients undergoing cardiac surgery. METHODS AND RESULTS Thirty-nine patients with ECG documented atrial fibrillation (AF) scheduled for coronary artery bypass grafting (CABG) with or without concomitant valve surgery were consecutively elected for epicardial RF ablation. Thirty-nine age- and gender-matched patients scheduled for CABG with or without concomitant valve surgery only and with documented AF served as controls. The follow-up after ablation was 32 +/- 11 months. The percentage of patients in sinus rhythm (SR) at long-term follow-up was 62 vs. 33% (P = 0.03) after ablation and no ablation, respectively. SR at 3 months was highly predictive of that at 32 months (sensitivity 95%, positive predictive value 86%). Long-term SR was associated with better QoL, fewer symptoms, higher ejection fraction, and smaller left and right atria than AF. CONCLUSION SR at 3 months was highly predictive of long-term SR that was associated with clinical improvement when compared with patients still in AF. AF at 3 months did not preclude a later stabilization to SR.

Slow and fast lung compartments in cystic fibrosis measured by nitrogen multiple-breath washout

Imaging studies describe significant ventilation defects across a wide range of cystic fibrosis (CF) related lung disease severity. These are unfortunately poorly reflected by phase III slope analysis-derived Scond and Sacin from multiple-breath washout (MBW). Methodology extending previous two-lung compartment model-based analysis is presented describing size and function of fast- and slow-ventilating lung compartments from nitrogen (N2) MBW and correlation to obstructive lung disease severity. In 37 CF subjects (forced expiratory volume in 1 s [FEV1] mean [SD] 84.8 [19.9] % predicted; abnormal lung clearance index [LCI] in 36/37, range 7.28-18.9) and 74 matched healthy controls, volume and specific ventilation of both fast and slowly ventilated lung compartments were derived from N2-based MBW with commercial equipment. In healthy controls lung emptying was characterized by a large compartment constituting 75.6 (8.4)% of functional residual capacity (FRC) with a specific ventilation (regional alveolar tidal volume/regional lung volume) of 13.9 (3.7)% and a small compartment with high specific ventilation (48.4 [15.7]%). In CF the slowly ventilated lung compartment constituted 51.9(9.1)% of FRC, with low specific ventilation of 5.3 (2.4)%. Specific ventilation of the slowly ventilated lung compartment showed stronger correlation with LCI (r2 = 0.70, P < 0.001) vs. Sacin (r2 = 0.44, P < 0.001) or Scond (no significant correlation). Overventilation of the fast lung compartment was no longer seen in severe CF lung disease. Magnitude and function of under- and overventilated lung volumes can be derived from routine N2 MBW in CF. Reported values agree with previous modelling-derived estimates of impaired ventilation and offer improved correlation to disease severity, compared with SnIII analysis.

Left ventricular diastolic function and right atrial size are important rhythm outcome predictors after intraoperative ablation for atrial fibrillation.

Background: Left ventricular (LV) diastolic function and right atrial (RA) size are not routinely included in preoperative echocardiographic examination in patients undergoing cardiac surgery with concomitant ablation for atrial fibrillation (AF). Objective: To investigate the role of echocardiographic variables including LV diastolic function and RA area in long‐term rhythm outcome prediction, in patients with documented AF undergoing intraoperative ablation concomitant to coronary artery bypass grafting (CABG). Methods: Thirty‐five consecutive patients, scheduled for CABG, and with a history of paroxysmal or permanent AF for 8.5 ± 11.3 years (mean ± SD) (median 5.8 years), were included in this prospective study. Echocardiography was performed prior to and 2.3 ± 0.4 years after the surgical procedure. Results: Both LA and RA areas, LV diastolic function, paroxysmal AF, and sinus rhythm (SR) preoperatively were associated with SR at long‐term follow‐up. In the multivariate analysis, RA area (P = 0.004), and decreased LV diastolic function preoperatively, measured as the maximal LV long‐axis relaxation velocity (P = 0.02), predicted SR at follow‐up. Conclusions: RA size and LV diastolic function may be important variables in prediction of long‐term rhythm outcome after intraoperative ablation for AF. (Echocardiography 2010;27:961‐968)

COPD ‘diagnosis’ based on spirometric reference equations

Introduction:  Chronic obstructive pulmonary disease (COPD) is suspected if the ratio between forced expired volume in 1 s (FEV1) and forced vital capacity is below 0.7 after bronchodilatation, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). As this ratio varies with age and gender, the lower limit of normality (LLN) of appropriate reference equations appears more adequate.

Impaired peripheral airway function in adults following repair of esophageal atresia

BACKGROUND Esophageal atresia (EA) often leads to persistent symptoms and impaired respiratory function in adulthood. The role of peripheral airways in this impairment has not been previously investigated. Furthermore, asthma-like symptoms are common in these patients. PURPOSE The purpose of this study was to investigate pulmonary outcome, including possible peripheral airway dysfunction, perhaps missed by conventional pulmonary function tests and to see if the diagnosis asthma was accurate. METHODS Twenty eight patients operated for EA in Gothenburg 1968-1983 answered a questionnaire regarding respiratory symptoms and underwent pulmonary function tests. Peripheral airway function was measured by multiple breath washout. RESULTS 22/28 (79%) patients had a history of respiratory symptoms. Abnormal peripheral airway function was found in 17 (61%) patients, while only 6 (21%) patients displayed values indicating central obstruction. Nine patients had restrictive disease. Airway hyperresponsiveness was frequent and associated with atopy and airway inflammation. However, respiratory symptoms or doctor-diagnosed asthma did not correlate with any specific lung function test abnormality. CONCLUSION Different lung function abnormalities are present in EA survivors, and peripheral airway disease is common. Classical asthma seems to be difficult to diagnose in this patient group. Given the high prevalence of respiratory morbidity, long-term follow-up of pulmonary function, including peripheral airway function, is warranted.

Prediction of BOS by the single-breath nitrogen test in double lung transplant recipients

BackgroundThe present study analyses the ability of the alveolar slope of the single-breath nitrogen washout test (N2-slope) to diagnose and predict the development of the bronchiolitis obliterans syndrome (BOS).MethodsWe present a retrospective analysis of 61 consecutive bilateral lung or heart-lung transplant recipients who were followed at regular control visits during a three year follow-up. The operating characteristics of the N2-slope to diagnose BOS and potential BOS (BOS 0-p) and to predict BOS were determined based on cut off values of 95% specificity.ResultsThe sensitivity of the N2-slope to identify BOS was 96%, and BOS 0-p 100%. The predictive ability to predict BOS with a N2-slope > 478% of the predicted normal was 56%, and if combined with a coincident FEV1 < 90% of the basal value, the predictive ability was 75%.ConclusionsThe predictive ability of either the N2-slope or of FEV1 to diagnose BOS is limited but the combination of the two appears useful. Follow-up protocols of bilateral lung and heart-lung transplant recipients should consider including tests sensitive to obstruction of the peripheral airways.

High tidal end expiratory flow - : an index of dynamic hyperinflation?

Dynamic hyperinflation is considered an important mechanism behind shortness of breath and reduced exercise capacity in chronic obstructive pulmonary disease (COPD) patients. Prevailing methods to assess dynamic hyperinflation are crude because of the large normal variation of both functional residual capacity and inspiratory capacity (IC). In the present study, we hypothesized that expiratory flow on a relatively high level near the end of tidal expiration is an indication of dynamic hyperinflation. A method to measure tidal end expiratory flow (TEEF), i.e. the flow between 0·6 s and 0·04 s before start of inspiration is presented and evaluated in 15 healthy subjects and 16 COPD patients. The COPD patients had more than twice as high TEEF values compared with the healthy subjects (45·4 ± 23·8 and 20·4 ± 7·3 ml s−1 respectively; mean ± SD; P = 0·0002, for TEEF at 0·4 s before start of inspiration). TEEF values correlated to IC, e.g. TEEF at 0·4 s before start of inspiration expressed as a fraction of mean expiratory flow, correlated to IC (% pred.) (r = 0·74; P<0·0001). These results justifies further testing of the relationship between TEEF and dynamic hyperinflation.

Respiratory symptoms and peripheral airways disease in a cross-sectional study on a random population sample.

Objectives Respiratory symptoms are associated with spirometry results but more strongly with smoking history, suggesting that alterations in the lung other than those revealed by spirometry contribute to cause symptoms. Smoking may cause obstruction of peripheral airways that is poorly detected by spirometry. The slope of phase III of the single-breath nitrogen (N2) test detects smoking-induced alterations in smokers before spirometry is impaired. The aim of the present investigation was to study the association between respiratory symptoms and the slope of phase III adjusting for spirometry results and smoking history. Design Single-centre retrospective cross-sectional study. Setting University hospital in Gothenburg, Sweden. Participants A random population sample of 430 elderly men. Methods The presence of seven different respiratory symptoms were analysed by a multiple logistic regression model in relation to spirometry results, smoking history (pack-years) and the slope of phase III in a population sample of 430 elderly men, age span 50–67 years. Furthermore, smoking normalised values of the slope of phase III were calculated and differences between subjects reporting/not reporting symptoms were tested. Results The presence of some cough symptoms was significantly associated with a steep slope of phase III also when adjusting for spirometry results and smoking history. Furthermore, smoking normalised slope of phase III was significantly steeper among subjects with cough symptoms compared to those without cough symptoms. Conclusions Cough symptoms may be an effect of abnormalities in peripheral airways at least among elderly men.