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.

Adults with small, unrepaired atrial septal defects have reduced cardiac index during exercise.

OBJECTIVES: Small, unrepaired atrial septal defects are considered a benign lesion with good prognosis. Recently, clinical and register-based studies discovered increased long-term mortality and morbidity. The nature of these findings is not fully understood. Therefore, MRI was performed to evaluate cardiac function at rest and during exercise. METHODS: Adults with open or spontaneously closed atrial septal defects and healthy, matched controls underwent MRI for evaluation of cardiac chamber volume. Quantitative flow scans measured blood flow in the ascending aorta and the proximal pulmonary artery at rest and during increasing supine exercise. RESULTS: In total, 15 open defects (39 ± 11 years) and 15 matched controls (38 ± 12 years) were included, along with 20 spontaneously closed (36 ± 13 years) and 20 controls (36 ± 11 years). Cardiac chamber volumes and flow measurements at rest were comparable between groups, as were heart rates and workloads during exercise. At maximal exercise, open defects reached 31% lower cardiac index and had 38% higher retrograde flow in the pulmonary artery than their controls, p < 0.01. Shunt ratio remained unchanged during exercise, 1.2 ± 0.2. Closed defects reached 18% lower cardiac index, p = 0.02, with comparable pulmonary retrograde flow. Maximal cardiac index was inversely correlated with increasing age for patients only. CONCLUSION: Adults with a small, open or spontaneously closed atrial septal defects exhibit markedly lower exercise capacity compared with healthy peers. Moreover, open defects exhibit higher retrograde flows with increasing exercise. Finally, increasing age is related to poorer results in patients but not healthy controls. Longitudinal studies are necessary in order to determine potential accelerated worsening of physical capacity along with age-related changes in patients.

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.

Sympathovagal imbalance decades after atrial septal defect repair: a long-term follow-up study.

OBJECTIVES: Recent evidence suggests that patients with a corrected atrial septal defect (ASD) have higher morbidity and mortality. An abnormal autonomic regulation of the heart may be a part of the explanation for this. Our objective was to study heart rate variability (HRV) in adults with a corrected ASD as a prominent tool to investigate the autonomic regulation of the heart. METHODS: Autonomic cardiac function was investigated in adults with either a surgically closed or percutaneously closed ASD and healthy control subjects. A 48-h Holter monitor was performed on each participant and HRV was assessed. RESULTS: A total of 17 patients with surgically closed ASDs, 18 percutaneously closed ASDs and 18 controls were included. The mean age in the surgical group, percutaneous group and controls was 32 ± 9, 28 ± 7 and 32 ± 10 years, respectively. The mean time since closure was 19 ± 8 years for the surgical group and 15 ± 5 years for the percutaneous group. The surgically closed ASD patients showed decreased HRV in all six parameters studied when compared to the controls. Similarly, the percutaneously closed ASDs showed decreased HRV in three out of six parameters when compared to controls. CONCLUSIONS: Adults with an ASD, whether closed surgically or percutaneously, have impaired HRV compared to their age- and sex-matched controls, more so in the patients with a surgically closed ASD. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (identifier: NCT03565471).

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.

Reduced biventricular contractility during exercise in adults with small, unrepaired ventricular septal defects: an echocardiographic study.

OBJECTIVES: Small ventricular septal defects are often considered to be without long-term haemodynamic consequences and so the majority remains unrepaired. However, we recently showed reduced functional capacity and altered right ventricular morphology in adults with small, unrepaired ventricular septal defects. The underlying mechanisms behind these findings remain unclear, and so, biventricular contractility during exercise was evaluated. METHODS: Adults with small, unrepaired ventricular septal defects and healthy controls were examined with echocardiography during supine bicycle exercise with increasing workload. Tissue velocity Doppler was used for evaluating isovolumetric acceleration and systolic velocities during exercise. RESULTS: In total, 34 patients with ventricular septal defects, a median shunt- ratio of 1.2 (26 ± 6 years), and 28 healthy peers (27 ± 5 years) were included. Right ventricular isovolumetric acceleration was lower in patients as compared with controls at rest (97 ± 40 vs 158 ± 43 cm/s2, P = 0.01) and at peak heart rate (222 ± 115 vs 410 ± 120 cm/s2, P < 0.01). Peak systolic velocities were similar at rest, but differed with exercise (13 ± 3 vs 16 ± 3 cm/s, P = 0.02). Left ventricular isovolumetric acceleration was lower in patients as compared with controls throughout the test (P < 0.01). Septal isovolumetric acceleration was similar at rest, but reduced during increasing exercise as compared with controls (220 ± 108 vs 303 ± 119 cm/s2, P = 0.03). Left ventricular isovolumetric acceleration was negatively correlated with the shunt- ratio, and right ventricular and septal peak systolic velocities were positively correlated with lower functional capacity. CONCLUSIONS: Altered biventricular contractility is present during exercise in adults with small, unrepaired ventricular septal defects. These results add to the growing number of studies showing that long-term outcome in unrepaired ventricular septal defects may not be benign.

Biventricular contractility during exercise in adults with small, unrepaired atrial septal defects.

BACKGROUND: Adult patients with a small, unrepaired atrial septal defect (ASD) have higher mortality and increased risk of several comorbidities compared to general population. Further, reduced submaximal and peak exercise capacity was recently demonstrated in these patients. The mechanisms behind these findings remain unexplained and, therefore, biventricular contractility during exercise was assessed by evaluating the force-frequency relationship in the same group of patients. METHODS: Adults patients with a small, unrepaired ASD and healthy age- and gender-matched controls were examined using echocardiography during supine bicycle exercise. Continuous tissue velocity Doppler was used to evaluate isovolumetric acceleration (IVA) and systolic velocities during an incremental workload protocol. All data were analyzed post hoc in a blinded fashion. RESULTS: We included 30 patients previously diagnosed with a small, unrepaired ASD (mean age 35 years, 63% female) and 25 controls (mean age 34 years, 64% female). Patients had similar values of IVA and systolic velocities at rest when compared with the healthy controls. Further, no differences in IVA was found at peak heart rate for neither the left ventricle (90 ± 39 vs 129 ± 68 cm/s2 , P = 0.1547) nor the right ventricle (128 ± 56 vs 154 ± 56 cm/s2 , 0.5691). There were no correlations between peak velocities and the lower exercise capacity previously reported in these patients. CONCLUSION: Adult patients with a small, unrepaired ASD have normal biventricular contractility at rest and during exercise when compared with healthy peers. Consequently, the pathophysiological mechanisms behind the impaired exercise capacity previously demonstrated in these patients remains unknown and will be a target for future work.

Cardiovascular magnetic resonance assessment of biventricular changes during vacuum bell correction of pectus excavatum.

BACKGROUND: Evidence of cardiac dysfunction in patients with pectus excavatum (PE) remains controversial. A growing number of studies report increased exercise tolerance following surgery. Nevertheless, many consider the correction of PE a cosmetic intervention, with post-operative changes ascribed to the concurrent growth of the young patient population. No studies have investigated non-invasively the immediate cardiac changes following relief of the deformity. The aim of this study was to assess cardiac function before and during temporary sternal elevation using the non-invasive vacuum bell (VB) device on young adults with PE. METHODS: Adult patients scheduled for surgical correction of PE underwent cardiac magnetic resonance imaging (CMRI) before and during the application of the VB. Steady-state free precession sequences were used for the evaluation of biventricular volume and function. Phase contrast sequences measured the aortic and pulmonary flow to calculate stroke index (SI). Scans were analyzed post hoc by the same investigator. A control group of healthy individuals was assessed in the same way. RESULTS: In total, 20 patients with PE (mean age 23±10 years) and 10 healthy individuals (mean age 25±6 years) underwent CMR before and during VB application. Before intervention, baseline cardiac volumes and function were similar between the groups, with patient-values in the low-to-normal range. Following VB application, PE patients revealed a 10% increase in biventricular SI. Furthermore, left ventricular end-diastolic volume index (LV EDVI) improved by 8% and right ventricular ejection fraction (RV EF) increased by 7%. These findings were not mirrored in the healthy individuals. No correlations were found between improved cardiac parameters and the baseline Haller index (HI) of PE patients. CONCLUSIONS: Non-invasive, momentary correction of PE is associated with an immediate improvement in SI, RV EF and LV EDVI, not observed in controls. The findings suggest that sternal depression in PE patients affects cardiac function.

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.

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.

Dynamic bicycle exercise to assess cardiac output at multiple exercise levels during magnetic resonance imaging.

PURPOSE: The aim was to establish a method for performing dynamic exercise during magnetic resonance imaging (MRI) using a slowly increasing workload protocol. METHODS: An ergometer bicycle with a step-wise, exercise protocol was used. Real-time phase-contrast MRI images of the aorta were obtained at each exercise step. RESULTS: In total, 40 participants completed the exercise protocol to reach a mean maximum cardiac output of 13.7±3.7l/min and a heart rate of 150±16beats/min at the highest exercise level. Less than 1% of scans were discarded due to poor quality. CONCLUSIONS: Dynamic, high intensity exercise is feasible during MRI.

Impaired cardiac output during exercise in adults operated for ventricular septal defect in childhood: a hitherto unrecognised pathophysiological response.

BACKGROUND: Recent studies have demonstrated that surgical ventricular septal defect closure in childhood is associated with reduced functional capacity and disruption of the right ventricular force-frequency relationship during exercise. To further describe long-term cardiac function, we performed a non-invasive assessment of cardiac index during exercise in adults having undergone surgery for ventricular septal defect in early childhood. METHODS: A total of 20 patients (surgical age 2.1±1.4 years, age at examination 22.1±2.2 years) and 20 healthy, matched controls (23.4±2.1 years at examination) underwent continuous supine bicycle ergometry during MRI. Their blood flow was recorded in the ascending aorta and the pulmonary trunk at increasing exercise levels. Cardiac index, retrograde flow, and vessel diameters were determined by blinded, post hoc analyses. RESULTS: The patient group had normal cardiac index at rest (2.9±0.7 L/minute/m2), which was comparable with that of the controls (3.0±0.6 L/minute/m2); however, they had a lower increase in cardiac index during exercise (reaching 7.3±1.3 L/minute/m2 at submaximal exercise) compared with controls (8.2±1.2 L/minute/m2), p<0.05. Patients had a significantly higher ascending aorta retrograde flow than controls at rest and throughout exercise. In the pulmonary artery, the retrograde flow was minimal at rest in both groups, but increased significantly in patients during exercise compared with controls. CONCLUSIONS: Young adults with a surgically closed ventricular septal defect have a reduced cardiac index during exercise compared with healthy, young adults. The impaired cardiac index appears to be related to an increasing retrograde flow in the pulmonary artery with progressive exertion.