Obstructive sleep apnea and road traffic accidents: a Danish nationwide cohort study.

STUDY OBJECTIVES: In this nationwide study, we investigate the risk and severity of all road traffic accidents in patients with obstructive sleep apnea (OSA). METHODS: We used the unique Danish registries to identify all Danish citizens receiving a diagnosis of OSA between 1995 and 2015. As a reference cohort, we randomly selected 10 sex- and age-matched citizens for each patient. We used Poisson regression to calculate the incidens rate ratio (IRR) for all road traffic accidents (motor vehicle, bicycle, and pedestrian) in both groups, and Cox proportional regression analysis to compare risk of first motor vehicle accident. Lastly, we used Fischers' Exact test to compare severity of motor vehicle accident between the two groups- RESULTS: We identified 48,168 patients with OSA, covering up to 24 years of follow-up. Patients with OSA had an increased risk of road traffic accidents when compared with the reference cohort (hazard ratio, 1.15; 95% CI, 1.10-1.20; IRR: 1.19; 95% CI, 1.14-1.29), especially motor vehicle accidents (hazard ratio, 1.29; 95% CI, 1.18-1.39; IRR 1.30; 95% CI, 1.20-1.42). The risk of accidents as pedestrian or bicyclist were not increased. Further, patients with OSA had a tendency to be involved in more severe motor vehicle accidents. CONCLUSIONS: This is the first nationwide study to estimate the risk of all road traffic accidents in patients with OSA. Our estimates show that patients with OSA have an increased risk of motor vehicle accidents, and greater severity of accidents, when compared with a large reference cohort.

Cardiopulmonary dysfunction in adults with a small, unrepaired ventricular septal defect: A long-term follow-up.

BACKGROUND: There are increasing reports of cardiac and exercise dysfunction in adults with small, unrepaired ventricular septal defects (VSDs). The primary aim of this study was to evaluate pulmonary function in adults with unrepaired VSDs, and secondly to assess the effects of 900 µg salbutamol on lung function and exercise capacity. METHODS: Young adult patients with small, unrepaired VSDs and healthy age- and gender-matched controls were included in a double-blinded, randomised, cross-over study. Participants underwent static and dynamic spirometry, impulse oscillometry, multiple breath washout, diffusion capacity for carbon monoxide, and ergometer bicycle cardiopulmonary exercise test. RESULTS: We included 30 patients with VSD (age 27 ±â€¯6 years) and 30 controls (age 27 ±â€¯6 years). Patients tended to have lower FEV1, 104 ±â€¯11% of predicted, compared with healthy controls, 110 ±â€¯14% (p = 0.069). Furthermore, the patient group had lower peak expiratory flow (PEF), 108 ±â€¯20% predicted, compared with the control group, 118 ±â€¯17% (p = 0.039), and showed tendencies towards lower forced vital capacity and increased airway resistance compared with controls. During exercise, the patients had lower oxygen uptake, 35 ±â€¯8 ml/min/kg (vs 47 ±â€¯7 ml/min/kg, p < 0.001), minute ventilation, 1.5 ±â€¯0.5 l/min/kg (vs 2.1 ±â€¯0.3 l/min/kg, p < 0.001) and breath rate, 48 ±â€¯11 breaths/min (vs 55 ±â€¯8 breaths/min, p = 0.008), than controls. CONCLUSION: At rest, young adults with unrepaired VSDs are no different in pulmonary function from controls. However, when the cardiorespiratory system is stressed, VSD patients demonstrate significantly impaired minute ventilation and peak oxygen uptake, which may be early signs of parenchymal dysfunction and restrictive airway disease. These abnormalities were unaffected by the inhalation of salbutamol.

Surgical closure of a ventricular septal defect in early childhood leads to altered pulmonary function in adulthood: A long-term follow-up.

BACKGROUND: The long-term outlook after surgical closure of ventricular septal defect (VSD) has traditionally been considered benign. However, there is an increasing awareness of not only late cardiac dysfunction, but also pulmonary abnormalities. The primary aim of this study was to describe pulmonary function in adults with a surgically repaired VSD, and secondarily to determine the effects of salbutamol on the potential abnormalities. METHODS: All patients (operated for a VSD in early childhood) and controls (age- and gender-matched) underwent static and dynamic spirometry, impulse oscillometry, multiple breath washout, diffusion capacity for carbon monoxide, and cardiopulmonary exercise testing. In a double-blinded, cross-over study, participants were randomized to inhalation of either 900 µg of salbutamol or placebo. The primary outcome was forced expiratory volume in 1 s. RESULTS: In total, 30 participants with a surgically closed VSD and 30 healthy controls were included. The VSD participants had a lower forced expiratory volume in 1 s (99 ±â€¯13% vs. 111 ±â€¯13%), p < 0.001, impaired forced vital capacity, (106 ±â€¯12% vs. 118 ±â€¯13%), p < 0.001, and lower peak expiratory flow, (95 ±â€¯18% vs. 118 ±â€¯19%), p < 0.001, than the control group. Also, the VSD group had a lower alveolar volume than the control group, (92 ±â€¯10% vs. 101 ±â€¯11%), p < 0.001, but there were no differences in the remaining pulmonary function parameters. Salbutamol reduced airway resistances in both groups, but exercise performance was not improved by salbutamol, however. CONCLUSIONS: Adults who have undergone surgical closure of a VSD in early childhood have reduced pulmonary function compared with controls, which is unaffected by inhalation of salbutamol.

Heart rate variability is impaired in adults after closure of ventricular septal defect in childhood: A novel finding associated with right bundle branch block.

BACKGROUND: Ventricular septal defects (VSDs) generally have benign long-term prognoses, but recent studies have indicated increased pulmonary vascular resistance. A potential tool for monitoring pulmonary artery pressure is heart rate variability, and therefore, the aim of this study was to assess heart rate variability in adults with a surgically repaired or unrepaired VSD. METHODS: In a long-term, follow-up study, three groups were included; VSD-patients operated in early childhood, patients with an open VSD, and controls. For each patient, 24-hour Holter monitoring was performed and heart rate variability was assessed. RESULTS: In total, 30 participants with a surgically closed VSD, 30 participants with an unrepaired VSD, and 36 controls were included. In the closed VSD group, there was a higher proportion of participants, who had low sNN50 (p = 0.005) and low sNN6% (p = 0.017) than in the other two groups. Similar differences were found when sNN50 was divided into increases and decreases (p = 0.007 and p = 0.005, respectively) as well as sNN6% (p = 0.014 and p = 0.014, respectively). Lastly, there was a higher proportion of patients in the closed VSD group with low rMSSD than in the other two groups (p = 0.005). For the closed VSD group, the proportion of participants with low total sNN50 (p = 0.046) and low total sNN6% (p = 0.046) were higher among participants with a complete right bundle branch block (RBBB) than among participants with no or an incomplete RBBB. CONCLUSIONS: Adults who had surgical VSD closure in early childhood had impaired heart rate variability and, particularly, participants with complete RBBB had lower heart rate variability.

Small unrepaired atrial septal defects display impaired exercise capacity compared with healthy peers.

OBJECTIVE: Adult patients with small, unrepaired atrial septal defects have an increased risk of pneumonia, atrial fibrillation, and stroke. Furthermore, they have higher late mortality than the background population. The functional capacity is unknown in these patients. Therefore, our objective was to determine exercise capacity in adult patients diagnosed with an unrepaired atrial septal defect compared to healthy controls. DESIGN: A cross-sectional study. PATIENTS: Adult patients with small, unrepaired atrial septal defects, aged 18-65, diagnosed between 1953 and 2011. INTERVENTIONS: Cardiopulmonary exercise test was performed using an incremental bicycle test and gas exchange was measured using breath-by-breath technique. OUTCOME MEASURES: Primary outcome was peak oxygen uptake, secondary outcome was maximal workload and ventilatory anaerobic threshold. RESULTS: We included 32 patients previously diagnosed with a small, unrepaired atrial septal defect and 16 healthy, age- and gender-matched controls (age 36.3 ± 13 years). Patients were divided into two groups based on whether the atrial septal defect was open (age 36.3 ± 11 years) or spontaneously closed (age 36.8 ± 14 years) since time of diagnosis. No differences in demographic characteristics or weekly exercise levels were found. Both patient groups reached lower peak oxygen uptake (open: 31.7 ± 11 mL/kg/min; spontaneously closed: 29.7 ± 6.9 mL/kg/min) compared with controls (42.6 ± 6.1 mL/kg/min; P = .0001). Workload (open: 2.6 ± 1.0 watt/kg; spontaneously closed: 2.5 ± 0.6 watt/kg) and aerobic capacity (open: 21.4 ± 8.7 mL/kg/min; spontaneously closed: 22.5 ± 6.5 mL/kg/min) was also poorer in patients compared to controls (workload: 3.5 ± 0.5 watt/kg; P = .0006, aerobic capacity: 31.3 ± 6.8 mL/kg/min; P = .0007). CONCLUSION: Adult patients with a diagnosis of small, unrepaired atrial septal defect have significantly impaired exercise capacity when compared to healthy controls. The impairment was present even if, by the time of assessment, the defect had closed spontaneously. The pathophysiological mechanisms behind the impaired exercise capacity demonstrated in these patients remain unexplained and will be a target for future work.

Exercise performance after salbutamol inhalation in non-asthmatic, non-athlete individuals: a randomised, controlled, cross-over trial.

BACKGROUND: Asthma is a frequent diagnosis in competitive sports, and inhaled ß2-agonists are commonly used by athletes. Although inhaled ß2-agonists do not seem to improve performance in athletes, it has remained uncertain whether they can increase exercise performance in non-athletes. OBJECTIVE: To investigate the effect of inhaled ß2-agonists on exercise performance in healthy non-athlete individuals. METHODS: In a double-blinded, placebo-controlled, cross-over trial, healthy, non-asthmatic, non-athlete individuals were randomised to inhalation of either 900 µg of salbutamol or placebo. Cardiopulmonary exercise testing, dynamic spirometry and impulse oscillometry were performed. The primary outcome was the effect from salbutamol on peak oxygen uptake, whereas secondary outcomes were breathing reserve and ventilation efficiency, and workload, heart rate, breath rate and minute ventilation at peak exercise under influence of salbutamol. RESULTS: A total of 36 healthy subjects with a mean age of 26±5 years were included. Salbutamol had no effect on peak oxygen uptake compared with placebo, 46.8±1.3 mL/kg/min versus 46.6±1.2 mL/kg/min, p=0.64. Salbutamol had no effect on workload, p=0.20, heart rate, p=0.23, breath rate, p=0.10, or minute ventilation, p=0.26, at peak exercise compared with placebo. Salbutamol lowered oxygen uptake, p=0.04, and workload, p=0.04, at anaerobic threshold compared with placebo. Forced expiratory volume in 1 s, 116%±13% of predicted, and peak expiratory flow, 122%±16% of predicted, increased after inhalation of salbutamol compared with placebo; 109%±13% and 117%±17%, respectively, p<0.01. Breathing reserve was found to be higher, 22%±2%, after salbutamol inhalation than after placebo, 16%±2%, p<0.01. CONCLUSION: Inhaled salbutamol did not improve peak oxygen uptake in healthy, non-asthmatic, non-athlete individuals compared with placebo. TRIAL REGISTRATION NUMBER: NCT02914652.

Biventricular morphology in adults born with a ventricular septal defect.

Ventricular septal defects - large, surgically closed or small, untreated - have demonstrated lower peak exercise capacity compared with healthy controls. The mechanisms behind these findings are not yet fully understood. Therefore, we evaluated biventricular morphology in adults with a ventricular septal defect using MRI. Adults with either childhood surgically closed or small, untreated ventricular septal defects and healthy controls underwent cine MRI for the evaluation of biventricular volumes and quantitative flow scans for measurement of stroke index. Scans were analysed post hoc in a blinded manner. In total, 20 operated patients (22±2 years) and 20 healthy controls (23±2 years) were included, along with 32 patients with small, unrepaired ventricular septal defects (26±6 years) and 28 controls (27±5 years). Operated patients demonstrated larger right ventricular end-diastolic volume index (103±20 ml/m2) compared with their controls (88±16 ml/m2), p=0.01. Heart rate and right ventricular stroke index did not differ between operated patients and controls. Patients with unrepaired ventricular septal defects revealed larger right ventricular end-diastolic volume index (105±17 ml/m2) compared with their controls (88±13 ml/m2), p<0.01. Furthermore, right ventricular stroke index was higher in unrepaired ventricular septal defects (53±12 ml/minute/m2) compared with controls (46±8 ml/minute/m2), p=0.02, with similar heart rates. Both patient groups' right ventricles were visually characterised by abundant coarse trabeculation. Positive correlations were demonstrated between right ventricular end-diastolic volume indices and peak exercise capacity in patients. Left ventricle measurements displayed no differences between groups. In conclusion, altered right ventricular morphology was demonstrated in adults 20 years after surgical ventricular septal defect repair and in adults with small, untreated ventricular septal defects.

Health-related quality-of-life after transapical transcatheter aortic valve implantation.

PURPOSE: Transcatheter aortic valve implantation (TA-TAVI) is a well-established treatment for aortic valve stenosis in high-risk patients and indications have been continuously expanding to also include intermediate-risk patients. However, in low-risk patients, experiences are still sparse and although clinical outcomes have been shown favorable results, HRQoL has remained unexplored. The aim of this report was to describe the long-term health-related quality-of-life (HRQoL) in low-risk patients randomized to TA-TAVI or surgical aortic valve replacement (SAVR). METHODS: In a prospective, randomized trial, patients with aortic valve stenosis were randomized to either TA-TAVI or SAVR. TA-TAVI was performed through a mini thoracotomy with the introduction of prosthesis via the apex of the heart and antegradely advancement over the pre-dilated native valve. SAVR was performed during cardiopulmonary bypass with resection of the native valve and replacement with a prosthesis valve through a median sternotomy. Afterwards, patients were followed yearly with echocardiography and HRQoL assessment. RESULTS: A total of 58 patients were included; 29 patients for TA-TAVI and 29 patients for SAVR. The only difference in HRQoL was found in the physical component summary after 1 year; 44 ± 9 in the TA-TAVI group compared with 36 ± 9 in the SAVR group, p = .03. There were no differences in any of the remaining timepoints in neither physical nor mental component summary, p = .19 and p = .98, respectively, and there were no differences in survival during the 5 years. CONCLUSIONS: In low-risk patients with aortic valve stenosis undergoing TA-TAVI, no differences appeared in HRQoL compared with SAVR during a 5-year follow-up period.