Psychiatric morbidity and work participation in patients with congenital ventricular septal defects: a case-controlled study.

BACKGROUND: The burden of psychiatric morbidity, level of education, and work participation is currently unknown in patients with congenital ventricular septal defects (VSD). METHODS: In a Danish population-based cohort study using nationwide medical registries the burden of psychiatric disorders, use of psychotropic agents, level of education, and work participation were examined in patients with isolated congenital VSD and controls from the general population matched by age and sex. Subjects with known chromosomal abnormalities were excluded. To compute estimates, Cox proportional regression model, Fine and Gray's competing risk regression, and Kaplan-Meier failure function were used. RESULTS: We included 8 006 patients and 79 568 controls born before 2018. Median follow-up was 23 years. Compared with controls, patients with VSD displayed a HR of 1.24 (95% CI: 1.17-1.32) for any psychiatric disorder where the hazard for intellectual disabilities was most pronounced [HR of 3.66 (95% CI: 2.98-4.50)]. The use of psychotropic agents was higher in patients compared with controls [HR 1.14 (95% CI: 1.09-1.20)]. The work participation was lower in patients with VSD compared with controls (P < 0.001) and was lower in patients with VSD with a psychiatric disorder compared with those without (P < 0.001). The 40-year cumulative incidence of permanent social security benefits was 29% in patients with psychiatric disorders (versus 21% in controls with psychiatric disorders) and 8% in patients without psychiatric disorders (versus 4% in controls). CONCLUSION: Patients with isolated VSD suffer from a higher burden of psychiatric disorders and display lower work participation compared with matched controls from the general Danish population. It is important to consider longer-term impacts on mental health, education, and subsequent employment in patients with VSD, in addition to cardiovascular effects, as these factors severely affect quality of life and have direct socioeconomic implications on an individual and societal level.

Health and Well-Being in Older Adults With a Surgically Closed or an Unrepaired Ventricular Septal Defect.

Background Older adults with a congenital ventricular septal defect (VSD) recently exhibited reduced heart rate variability and exercise capacity. It is unknown whether these findings affect health-related quality of life. Methods and Results Adults with VSDs and healthy controls, all concurrently included as part of another clinical study, completed the Danish National Health Survey questionnaire. Questionnaire data distributed to the general population were included and matched 10:1 with patients. Thirty patients with surgically closed VSDs (mean±SD age, 51±8 years), 300 adults from the general population (mean±SD age, 50±8 years), and 30 controls (mean±SD age, 51±9 years), as well as 30 patients with unrepaired VSDs (mean±SD age, 55±11 years), 300 adults from the general population (mean±SD age, 55±12 years), and 30 controls (mean±SD age, 55±10 years) completed the questionnaire. Educational level, social relations, and physical activity were comparable between groups. A larger proportion of patients with unrepaired VSDs compared with the general population experienced migraine (47% versus 24%; P=0.04), whereas more patients with surgically closed VSDs were affected by depression (13% versus 4%; P=0.02). For health-related quality of life, patients with surgically closed VSDs reported lower physical functioning (P<0.01), physical component summary (P<0.01), general health perception (P<0.01), and higher stress score (P=0.03) compared with the general population and healthy controls. Patients with unrepaired VSDs reported lower scores on physical functioning (P=0.03), bodily pain (P<0.01), and mental health (P=0.02), and a higher stress score (P=0.03), than controls. Conclusions Older patients with VSDs report lower self-perceived physical functioning, lower general health, and higher stress levels, all in line with previous findings, like lower exercise capacity and dysfunctional cognitive abilities, in adults with VSDs. Incessant follow-up is paramount, as neither successfully closed nor hemodynamically insignificant VSD is equivalent with untroubled healthy aging. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03684161.

Mortality in Patients With Ebstein Anomaly.

BACKGROUND: Low birth prevalence and referral bias constitute significant obstacles to elucidating the natural history of Ebstein anomaly (EA). OBJECTIVES: An extensive 2-country register-based collaboration was performed to investigate the mortality in patients with EA. METHODS: Patients born from 1970 to 2017 and diagnosed with EA were identified in Danish and Swedish nationwide medical registries. Each patient was matched by birth year and sex with 10 control subjects from the general population. Cumulative mortality and HR of mortality were computed using Kaplan-Meier failure function and Cox proportional regression model. RESULTS: The study included 530 patients with EA and 5,300 matched control subjects with a median follow-up of 11 years. In the EA cohort, 43% (228) underwent cardiac surgery. Cumulative mortality was lower for patients diagnosed in the modern era (the year 2000 and later) than for those diagnosed in the prior era (P < 0.001). Patients with isolated lesion displayed lower cumulative mortality than patients with complex lesions did (P < 0.001). Patients with a presumed mild EA anatomy displayed a 35-year cumulative mortality of 11% (vs 4% for the matched control subjects; P < 0.001), yielding an HR for mortality of 6.0 (95% CI: 2.7-13.6), whereas patients with presumed severe EA demonstrated an HR of 36.2 (95% CI: 15.5-84.4) compared with control subjects and a cumulative mortality of 18% 35 years following diagnosis. CONCLUSIONS: Mortality in patients with EA is high irrespective of presence of concomitant congenital cardiac malformations and time of diagnosis compared with the general population, but overall mortality has improved in the contemporary era.

Lifetime Burden of Morbidity in Patients With Isolated Congenital Ventricular Septal Defect.

Background The lifetime burden of morbidity in patients with isolated congenital ventricular septal defect (VSD) is not completely described. Methods and Results In a population-based cohort study in Denmark using nationwide medical registries, we included 8006 patients diagnosed with a congenital VSD before 2018 along with 79 568 randomly selected controls from the general Danish population matched by birth year and sex. Concomitant congenital cardiac malformations and chromosomal abnormalities were excluded. Cox proportional hazard regression, Fine and Gray competing risk regression, and Kaplan-Meier survival function were used to estimate burden of morbidity, compared with matched controls. Median follow-up was 23 years (interquartile range, 11-37 years). The hazard ratio (HR) of heart failure was high in both patients with unrepaired and surgically closed VSD when compared with their corresponding matched controls (5.4 [95% CI, 4.6-6.3] and 30.5 [95% CI, 21.8-42.7], respectively). Truncated analyses with time from birth until 1 year after VSD diagnosis (unrepaired) or surgery (surgically closed) censored revealed reduced but persisting late hazard of heart failure. Similarly, the late hazard of arrhythmias and pulmonary arterial hypertension was high irrespective of defect closure. The HR of endocarditis was 28.0 (95% CI, 19.2-40.9) in patients with unrepaired defect and 82.7 (95% CI, 37.5-183.2) in patients with surgically closed defect. The increased HR diminished after VSD surgery. In general, the incidence of morbidity among patients with unrepaired VSD accelerated after the age of 40 years. Conclusions Patients with isolated congenital VSD carry a substantial burden of cardiovascular morbidity throughout life, irrespective of defect closure.

Survival of patients with congenital ventricular septal defect.

AIMS: The long-term survival of patients with isolated congenital ventricular septal defect (VSD) is not well described. The aim of this study was to describe the survival of a national cohort of patients with VSD compared with the general population. METHODS AND RESULTS: Using Danish nationwide medical registries, all patients diagnosed with congenital VSD (n = 9,136) in the period 1977-2018 were included. Patients with chromosomal abnormalities and concomitant congenital cardiac malformations other than atrial septal defect were excluded. Each patient was matched by birthyear and sex with ten controls from the general Danish population. Kaplan-Meier survival function and Cox proportional hazard regression were used to compute survival and mortality risk. Median follow-up was 22 years (interquartile range: 11-37). VSD patients displayed lower survival (P<0.001) yielding a hazard ratio (HR) for mortality of 2.7 [95% confidence interval (CI): 2.4-3.0] compared with matched controls. The adjusted HR for mortality among patients with unrepaired VSD was 2.7 (95% CI: 2.4-3.0) and 2.8 (95% CI: 2.1-3.7) for patients with surgically closed VSD. Stratified by era of VSD diagnosis, the HR for mortality was 3.2 (95% CI: 2.8-3.7) for unrepaired patients diagnosed before 1990 and 2.4 (95% CI: 2.0-2.7) for patients diagnosed later. Cardiac-related death was the commonest cause of death among unrepaired (30%) and surgically closed (65%) patients. CONCLUSION: Patients with VSD had lower survival compared with the general population. The HR for mortality was increased over 2.5-fold in patients with unrepaired defect (Eisenmenger syndrome excluded) and over 1.5-fold in patients with surgically closed defect (excluding surgical mortality).

Cardiac Arrhythmias and Impaired Heart Rate Variability in Older Patients With Ventricular Septal Defects.

Background Congenital ventricular septal defects (VSDs) are considered to have benign long-term outcome when treated correctly in childhood. However, abnormal parameters are described in younger adults, including impaired heart rate variability (HRV). It is not known whether such abnormalities will deteriorate with age. Therefore, HRV and cardiac events, such as premature ventricular contraction, were evaluated in patients aged >40 years with congenital VSDs and compared with healthy peers. Methods and Results A total of 30 surgically closed VSDs (51±8 years, repair at median age 6.3 years with total range 1.4-54 years) with 30 healthy controls (52±9 years) and 30 small, unrepaired VSDs (55±12 years) with 30 controls (55±10 years) were all equipped with a Holter monitor for 24 hours. Compared with healthy peers, surgically closed patients had lower SD of the normal-to-normal (NN) interbeat interval (129±37 versus 168±38 ms; P<0.01), SD of the average NN intervals for each 5-minute segment of a 24-hour HRV recording (116±35 versus 149±35 ms; P<0.01) and 24-hour triangular index (31±9 versus 44±11; P<0.01). SD of the NN intervals, SD of the average NN intervals for each 5-minute segment of a 24-hour HRV recording, and triangular index were comparable between unrepaired VSDs and healthy peers. SD of the NN intervals was <100 ms in 22% of surgically closed and 10% of unrepaired VSDs, whereas controls were within normal ranges. A high number of premature ventricular contractions (>200 events) was registered in 57% of surgical patients compared with 3% of controls (P<0.01), and 53% of unrepaired VSDs compared with 10% in controls (P<0.01). Conclusions Adults aged >40 with congenital VSDs demonstrate impaired HRV, mainly among surgically closed VSDs. More than half demonstrated a high number of premature ventricular contractions. These novel findings could indicate long-term cardiovascular disturbances. This necessitates continuous follow-up of VSDs throughout adulthood.

Mortality burden in patients born with Ebstein's anomaly: a 40-year nationwide cohort study.

AIMS: Survival rates for unoperated patients with Ebstein's anomaly (EA) are unknown. We estimated overall long-term mortality in operated and unoperated EA patients, compared with the general population in Sweden. METHODS AND RESULTS: Using national medical registries, Swedish individuals born 1970-93 and diagnosed with EA between 1970 and 2011 were included. The hazard ratio for overall mortality for EA patients (n = 216) vs. the matched comparison cohort (n = 2160) was 43.7 [95% confidence interval (CI): 24.8-82.5]. Mortality risk for EA patients (vs. controls) decreased as birth period progressed, with hazard ratios declining from 63.6 (95% CI: 26.3-191.8) for those born in the 1970s to 34.4 (95% CI: 15.8-83.1) for those born in the 1980s and 20.2 (95% CI: 1.6-632.5) for those born at the beginning of 1990s. The overall mortality hazard ratios for unoperated and operated patients with EA (vs. controls) were 30.2 (95% CI: 13.8-73.3) and 63.7 (95% CI: 28.1-172.5), respectively. The risk of mortality among unoperated EA patients (vs. controls) declined with progressing birth period, with hazard ratios declining from 58.4 (95% CI: 15.1-415.2) in the 1970s to 22.9 (95% CI: 8.0-75.3) in the 1980s and 10.2 (95% CI: 0.3-395.9) in the 1990s. CONCLUSION: Overall all-cause mortality for patients with EA declined dramatically from 64 times to 20 times that of controls without EA, from the 1970s to the early 1990s. Unoperated patients with EA had better survival than did operated patients, possibly reflecting the higher severity of disease or more severe associated cardiac defects in patients undergoing surgery.

Functional Capacity Past Age 40 in Patients With Congenital Ventricular Septal Defects.

Background Ventricular septal defects (VSD), when treated correctly in childhood, are considered to have great prognoses, and the majority of patients are discharged from follow-up when entering their teens. Young adults were previously found to have poorer functional capacity than healthy peers, but the question remains whether functional capacity degenerates further with age. Methods and Results A group of 30 patients with surgically closed VSDs (51±8 years) with 30 matched, healthy control participants (52±9 years) and a group of 30 patients with small unrepaired VSDs (55±12 years) and 30 matched control participants (55±10 years) underwent cardiopulmonary exercise testing using an incremental workload protocol and noninvasive gas measurement. Peak oxygen uptake was lower in participants with closed VSDs than matched controls (24±7 versus 34±9 mL/min per kg, P<0.01) and with unrepaired VSDs than matched controls (26±5 versus 32±8 mL/min per kg, P<0.01). Patients demonstrated lower oxygen uptake from exercise levels at 20% of maximal workload compared with respective control groups (P<0.01). Peak ventilation was lower in patients with surgically closed VSDs than control participants (1.0±0.3 versus 1.4±0.4 L/min per kg, P<0.01) but similar in patients with unrepaired VSDs and control participants (P=0.14). Exercise capacity was 29% lower in older patients with surgically closed VSDs than healthy peers, whereas younger patients with surgically closed VSDs previously demonstrated 18% lower capacity compared with peers. Older patients with unrepaired VSDs reached 21% lower exercise capacity, whereas younger patients with unrepaired VSDs previously demonstrated 17% lower oxygen uptake than healthy peers. Conclusions Patients with VSDs demonstrate poorer exercise capacity than healthy peers. The difference between patients and control participants increased with advancing age-and increased most in patients with operated VSDs-compared with previous findings in younger patients. Results warrant continuous follow-up for these simple defects.

Comparison of Outcomes in Adults With Ventricular Septal Defect Closed Earlier in Life Versus Those in Whom the Defect Was Never Closed.

Ventricular septal defects (VSDs) have recently demonstrated poorer functional outcome with disrupted ventricular contractility during exercise in young patients. It is not known whether this will change with age. Therefore, echocardiography was performed in older patients with congenital VSDs, either surgically closed or unrepaired and all without Eisenmenger physiology, to compare functional outcomes with healthy peers. Transthoracic echocardiography was performed at rest and during supine bicycle exercise, with tissue velocity Doppler for assessment of primary end points: isovolumetric acceleration and systolic velocities. In total, 30 surgically closed VSDs (51 ± 8 years) with 30 healthy controls (52 ± 9 years) and 30 unrepaired VSDs (55 ± 12 years) with 30 matched controls (55 ± 10 years) were included. Surgical patients displayed lower right ventricular (RV) systolic and early diastolic-filling velocities compared with controls, p <0.01, lower tricuspid annular plane systolic excursion (17.8 ± 5 vs 22.7 ± 3mm, p <0.01) and lower fractional area change (37.8 ± 6 vs 46.4% ± 7%, p <0.01). Unrepaired VSDs also had lower RV fractional area change than matched controls (39.9 ± 7 vs 48.4% ± 7%, p <0.01). Both patient groups had more tricuspid regurgitation and larger RV outflow tract dimensions than controls, p <0.01. During exercise, isovolumetric acceleration and systolic velocities were lower in both patient groups compared with controls, with the difference increasing with workload level. In conclusion, adults in their mid-50s with surgically closed or unrepaired VSDs have abnormal RV function at rest, with even more pronounced differences during exercise. These results suggest that a VSD, whether repaired early or considered hemodynamically insignificant, is not a benign lesion and continuous follow-up of adults is warranted.

Pulmonary Function in Older Patients With Ventricular Septal Defect.

To better understand the evolvement of the pulmonary dysfunction in the aging ventricular septal defect (VSD) patient, we invited adult patients with a congenital VSD and healthy age- and gender-matched controls for static and dynamic spirometry, impulse oscillometry, multiple breath washout, and diffusion capacity for carbon monoxide testing. Primary outcome was forced expiratory volume in 1 second. In total, 30 patients with a surgically corrected VSD (mean age 51 ± 8 years), 30 patients with a small, unrepaired VSD (mean age 55 ± 1 years), and 2 groups of 30 age- and gender-matched, healthy controls (mean age 52 ± 9 years and 55 ± 10 years, respectively) were included. Median age of radical surgery was 6.3 (total range: 1.4 to 54) years and median follow-up after surgery was 40 years (total range: 3.4 to 54). Compared with healthy matched controls, surgically corrected VSD patients had lower forced expiratory volume in 1 second, 87 ± 19% versus 105 ± 14% of predicted, p <0.01, lower forced vital capacity, 92 ± 16% versus 107 ± 13% of predicted, p <0.01, and lower peak expiratory flow, 100 ± 21% versus 122 ± 16% of predicted, p <0.01. Furthermore, corrected VSD patients revealed increased airway resistance in the small airways, 30 ± 22% versus 15 ± 14% of total resistance, p <0.01, and reduced diffusion capacity, 84 ± 12% versus 101 ± 11%, p <0.01. Patients with a small, unrepaired VSD had comparable pulmonary function to their matched controls. In conclusion, VSD patients 40 years of age or older demonstrated significant impaired pulmonary function in terms of reduced dynamic pulmonary function, increased airway resistance in the small airways, and reduced diffusion capacity up to 54 years after defect closure compared with healthy age- and gender-matched controls.

Disappearance of the shunt and lower cardiac index during exercise in small, unrepaired ventricular septal defects.

OBJECTIVES: Clinical studies have revealed decreased exercise capacity in adults with small, unrepaired ventricular septal defects. Increasing shunt ratio and growing incompetence of the aortic and pulmonary valve with retrograde flow during exercise have been proposed as reasons for the previously found reduced exercise parameters. With MRI, haemodynamic shunt properties were measured during exercise in ventricular septal defects. METHODS: Patients with small, unrepaired ventricular septal defects and healthy peers were examined with MRI during exercise. Quantitative flow scans measured blood flow through ascending aorta and pulmonary artery. Scans were analysed post hoc where cardiac index, retrograde flows, and shunt ratio were determined. RESULTS: In total, 32 patients (26 ± 6 years) and 28 controls (27 ± 5 years) were included. The shunt ratio was 1.2 ± 0.2 at rest and decreased to 1.0 ± 0.2 at peak exercise, p < 0.01. Aortic cardiac index was lower at peak exercise in patients (7.5 ± 2 L/minute/m2) compared with controls (9.0±2L l/minute/m2), p<0.01. Aortic and pulmonary retrograde flow was larger in patients during exercise, p < 0.01. Positive correlation was demonstrated between aortic cardiac index at peak exercise and previously established exercise capacity for all patients (r = 0.5, p < 0.01). CONCLUSIONS: Small, unrepaired ventricular septal defects revealed declining shunt ratio with increasing exercise and lower aortic cardiac index. Patients demonstrated larger retrograde flow both through the pulmonary artery and the aorta during exercise compared with controls. In conclusion, adults with unrepaired ventricular septal defects redistribute blood flow during exercise probably secondary to a more fixed pulmonary vascular resistance compared with age-matched peers.

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.

Successful resection of oesophageal adenocarcinoma 16 years after heart transplantation-a case report.

INTRODUCTION: With improving results of heart transplantation and subsequently increasing survival, long-term complications such as neoplastic malignancies are more often being discovered. PRESENTATION OF CASE: In this report, we present a unique case of successful oesophagus resection with gastric pull-up, on a heart-transplanted patient diagnosed with oesophageal adenocarcinoma. DISCUSSION: With the growing number of long-term surviving heart transplanted patients, the number of neoplasia in this patient-group will subsequently grow. Since physical condition and quality of life in long-term surviving heart transplanted patients is comparable to the general population, and since surgical treatment remains the mainstay of treatment for localised oesophageal carcinoma in non-heart transplanted patients, a larger subgroup of heart transplanted patients will most likely be considered for cancer surgery. CONCLUSION: Our case demonstrates the possibility of operating on the heart transplanted patient-group, and supports the option, that well-managed heart transplantation not should be a limiting factor, when deciding whether a patient is a candidate for surgical intervention or not.