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Patients with pulmonary hypertension associated with congenital heart disease survive longer with preserved right ventricular (RV) function compared with those with primary pulmonary hypertension. The purpose of this study was to test the hypothesis that superior RV performance can be demonstrated, at baseline and when challenged with increased RV afterload, in lambs with chronic left-to-right cardiac shunts compared with control lambs. A shunt was placed between the pulmonary artery and the aorta in fetal lambs (shunt). RV pressure-volume loops were obtained 4 wk after delivery in shunt and control lambs, before and after increased afterload was applied using pulmonary artery banding (PAB). Baseline stroke volume (8.7 ± 1.8 vs. 15.8 ± 2.7 ml, P = 0.04) and cardiac index (73.0 ± 4.0 vs. 159.2 ± 25.1 ml·min(-1)·kg(-1), P = 0.02) were greater in shunts. After PAB, there was no difference in the change in cardiac index (relative to baseline) between groups; however, heart rate (HR) was greater in controls (168 ± 7.3 vs. 138 ± 6.6 beats/min, P = 0.01), and end-systolic elastance (Ees) was greater in shunts (2.63 vs. 1.31 × baseline, P = 0.02). Control lambs showed decreased mechanical efficiency (71% baseline) compared with shunts. With acute afterload challenge, both controls and shunts maintained cardiac output; however, this was via maladaptive responses in controls, while shunts maintained mechanical efficiency and increased contractility via a proposed enhanced Anrep effect-the second, slow inotropic response in the biphasic ventricular response to increased afterload, a novel finding in the RV. The mechanisms related to these physiological differences may have important therapeutic implications.

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). [ABSTRACT FROM AUTHOR]

Background: Non-invasive imaging markers in patients with repaired tetralogy of Fallot (rTOF) are still being investigated to inform clinical decision making. Atrial function is a prognostic indicator in many acquired and congenital heart diseases. We sought to examine the relationship between cardiac MRI (CMR)-derived indices of left atrial (LA) function, native left ventricular (LV) T1 values, biventricular systolic function, and exercise capacity in rTOF. Methods: Sixty-six patients with rTOF without prior pulmonary valve replacement who underwent CMR (median age 18.5 years) were identified. Twenty-one adult rTOF patients (age range 19–32 years) were compared with 20 age-matched healthy volunteers (age range 19–34 years). LA reservoir, conduit, and pump global longitudinal strain (GLS) and strain rate (SR) were determined by tissue tracking. Native LV T1 values were measured on rTOF patients. Pearson correlations were performed to determine bivariate associations. Results: Adult rTOF patients had higher pump GLS, pump:conduit, and pump:reservoir GLS ratios, and lower conduit:reservoir GLS ratio, LV ejection fraction (EF), and right ventricular EF compared to controls (p < 0.001 for each comparison). LA conduit:reservoir GLS and pump:reservoir GLS had correlations to native LV T1 (ρ = 0.26, p = 0.03 and ρ = − 0.26, p = 0.03, respectively). LA reservoir SR had positive correlation to RV EF (ρ = 0.27, p = 0.03). There were no statistically significant correlations between LA function and exercise capacity. Conclusions: LA function is altered in adolescent and young adult patients with rTOF indicating worse diastolic function and relates to increasing native LV T1 values. Future studies are indicated to investigate the progression of adverse atrial-ventricular interactions and poor outcomes in this population. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide 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. [ABSTRACT FROM AUTHOR]

Adult survivors of congenital heart disease form a continuously growing population, as each successive cohort graduating from pediatric care expands the total number of patients worldwide. Consequently, there is an increasing interest and study of their late pathophysiology, the understanding of which can only truly be understood during very long-term follow-up. Indeed, we have already learned that, for some patient groups, hitherto unexpected problems may only develop decades after surgery. Consequently, many patients require careful follow-up in ACHD clinics throughout life. However, in the most frequent congenital heart disease, ventricular septal defect (VSD), most guidelines recommend that specialized follow-up in ACHD clinics may only be indicated for those patients with significant residual anatomic problems, or overt pulmonary hypertension. Indeed, the late outcome for patients undergoing ‘uncomplicated’ repair in childhood has been described as benign. However, recent data suggest that such characterization may be premature. Several studies have described abnormalities of right ventricular structure and function which, in turn, may be directly related to abnormal functional capacity when formally tested. Furthermore, the longer-term implications of e.g. right bundle branch block and chronotropic incompetence continue to be explored. In this review we will examine these emerging data, and discuss whether amendments to the international guidelines for these patients' may be justified. [ABSTRACT FROM AUTHOR]

Background Adults with single ventricle physiology palliated with a Fontan circulation experience high mortality due to circulatory failure. Renin-angiotensin-aldosterone system (RAAS) genotype contributes to adverse cardiovascular outcomes in acquired heart failure. This study evaluated associations between RAAS genotype, ventricular mass and function in a contemporary cohort of adults with a Fontan circulation. Methods This single-center prospective study included adults (n = 106) seen after the Fontan operation (mean age 27 ± 9 years). Patients were genotyped for 5 pro-hypertrophic RAAS gene polymorphisms. Serum BNP, ventricular mass and function, and clinical events were compared between those with ≥ 2 homozygous risk genotypes (“high-risk”, n = 31) versus those with ≤ 1 homozygous risk genotypes (“low risk”, n = 75). Results “High-risk” genotype was associated with diastolic dysfunction and higher serum BNP levels. There was no association between RAAS genotype and either ventricular mass or systolic function. During a mean follow-up duration of 9.5 ± 7.6 years, late Fontan failure occurred in 20% (n = 21) of patients, including 7 deaths. Serum BNP emerged as an independent predictor of late Fontan failure (HR 1.11 [CI 1.01–1.23] for each 50 unit increase in BNP, p = 0.04) and death alone (HR 1.25 [CI 1.07–1.47] for each 50 unit increase in BNP, p = 0.006). RAAS genotype was not associated with adverse clinical events. Conclusions Fontan failure is common among adults with single ventricle physiology. RAAS genotype is not associated with increased ventricular mass but does appear to influence diastolic function late after the Fontan operation. Elevated BNP is an independent predictor of Fontan failure and mortality in adulthood. [ABSTRACT FROM AUTHOR]

Patients with pulmonary hypertension associated with congenital heart disease survive longer with preserved right ventricular (RV) function compared with those with primary pulmonary hypertension. The purpose of this study was to test the hypothesis that superior RV performance can be demonstrated, at baseline and when challenged with increased RV afterload, in lambs with chronic left-to-right cardiac shunts compared with control lambs. A shunt was placed between the pulmonary artery and the aorta in fetal lambs (shunt). RV pressure-volume loops were obtained 4 wk after delivery in shunt and control lambs, before and after increased afterload was applied using pulmonary artery banding (PAB). Baseline stroke volume (8.7 ± 1.8 vs. 15.8 ± 2.7 ml, P = 0.04) and cardiac index (73.0 ± 4.0 vs. 159.2 ± 25.1 ml.min-1.kgmin-1, P = 0.02) were greater in shunts. After PAB, there was no difference in the change in cardiac index (relative to baseline) between groups; however, heart rate (HR) was greater in controls (168 ± 7.3 vs. 138 ± 6.6 beats/min, P = 0.01), and end-systolic elastance (Ees) was greater in shunts (2.63 vs. 1.31 × baseline, P = 0.02). Control lambs showed decreased mechanical efficiency (71% baseline) compared with shunts. With acute afterload challenge, both controls and shunts maintained cardiac output; however, this was via maladaptive responses in controls, while shunts maintained mechanical efficiency and increased contractility via a proposed enhanced Anrep effect-the second, slow inotropic response in the biphasic ventricular response to increased afterload, a novel finding in the RV. The mechanisms related to these physiological differences may have important therapeutic implications. [ABSTRACT FROM AUTHOR]

Background: Adverse ventricular remodeling after tetralogy of Fallot (TOF) repair is associated with diffuse myocardial fibrosis. Objective: The goal of this study was to measure post-contrast myocardial T1 in pediatric patients after TOF repair as surrogates of myocardial fibrosis. Materials and methods: Children after TOF repair who underwent cardiac magnetic resonance imaging with T1 mapping using the modified look-locker inversion recovery (MOLLI) sequence were included. In addition to routine volumetric and flow data, we measured post-contrast T1 values of the basal interventricular septum, the left ventricular (LV) lateral wall, and the inferior and anterior walls of the right ventricle (RV). Results were compared to data from age-matched healthy controls. Results: The scans of 18 children who had undergone TOF repair and 12 healthy children were included. Post-contrast T1 values of the left ventricular lateral wall (443 ± 54 vs. 510 ± 77 ms, P = 0.0168) and of the right ventricular anterior wall (333 ± 62 vs. 392 ± 72 ms, P = 0.0423) were significantly shorter in children with TOF repair than in controls, suggesting a higher degree of fibrosis. In children with TOF repair, but not in controls, post-contrast T1 values were shorter in the right ventricle than the left ventricle and shorter in the anterior wall of the right ventricle than in the inferior segments. In the TOF group, post-contrast T1 values of the RV anterior wall correlated with the RV end-systolic volume indexed to body surface area ( r = 0.54; r = 0.30; P = 0.0238). Conclusion: In children who underwent tetralogy of Fallot repair the myocardium of both ventricles appears to bear an abnormally high fibrosis burden. [ABSTRACT FROM AUTHOR]

Objective(s): To evaluate the measurement of cardiac output (CO) using continuous electrical bioimpedance cardiography (Physioflow; Neumedx, Philadelphia, PA) (COPF) with a simultaneous direct Fick measurement (COFICK) in children with congenital heart disease. Design: A prospective cohort study comparing 2 methods of measurement of CO. Setting: A quaternary university-affiliated pediatric hospital. Participants: Children undergoing cardiac catheterization for clinical care. Interventions: The Physioflow measured continuous real time CO in 15-second epochs and simultaneous measurement of cardiac output by direct Fick (with mass spectrometry to assess VO2) were acquired. Measurements and Main Results: Sixty-five patients were recruited, and data from 56 (25 males) were adequate for analysis. The median age at study was 3.5 years (range, 0.4-16.6 years), and the median body surface area was 0.62 m2 (range, 0.31-1.71). There were 25 of 56 (45%) with univentricular physiology. A total of 19,228 Physioflow data points were available for the analysis of which 14,569 (76%) were valid; 96% of the invalid measurements were identified as artifacts by the device. The average cardiac index of valid measurements was 3.09 ± 0.72 L/min/m2. Compared with the Fick CO, the mean bias was −0.09 L/min, but the 95% limits of agreement were −3.20 to +3.01 L/min/m2. Consequently, only 20 of 56 (36%) of measurements were within 20%, and 31 of 56 (55%) of measurements were within 30% of each other. Conclusions: Compared with measurements made by direct Fick, CO measured using the Physioflow device was unreliable in anesthetized children with congenital heart disease. [ABSTRACT FROM AUTHOR]

Background: Adult patients with repaired tetralogy of Fallot (rTOF) often have diminished exercise capacity. The primary objective of this study was to examine whether abnormalities of biventricular function play a role in exercise limitation in patients with rTOF. Methods: This was a retrospective review of 99 adult patients with rTOF. Right ventricular (RV) and left ventricular (LV) function were assessed echocardiographically using the myocardial performance index (MPI). Maximal oxygen consumption (VO2 Max) was measured during a level 1 cardiopulmonary exercise test. Results: The mean age of the cohort was 34 ± 11 years (50% females). Although most of the patients reported good functional capacity, the peak Vo 2max was decreased at 22 ± 6 mL/kg per minute (66% ± 13% predicted Vo 2max for age and sex). The mean RV and LV MPI were 0.30 ± 0.07 and 0.42 ± 0.09, respectively. In the multivariate model, higher RV MPI (P = .04) and LV MPI (P = .005) values, representing impaired ventricular function, were associated with diminished Vo 2max. There was a significant correlation between the RV and LV MPI (r = 0.54, P = .001). Conclusions: Impairment of RV and LV function, as measured by MPI, is associated with diminished exercise capacity in patients with repaired tetralogy of Fallot. Furthermore, there is a linear relationship between the RV and LV function suggesting that ventricular interactions are contributing to the limited exercise capacity in this group of patients. Strategies aimed at preserving biventricular function or improving adverse ventricular interactions could help to improve functional capacity in these patients. [Copyright &y& Elsevier]

At the end of every heartbeat, cardiac myocytes must relax to allow filling of the heart. Impaired relaxation is a significant factor in heart failure, but all pathways regulating the cardiac relaxation apparatus are not known. Haploinsufficiency of the T-box transcription factor Tbx5 in mouse and man causes congenital heart defects (CHDs) as part of Holt-Oram syndrome (HOS). Here, we show that haploinsufficiency of Tbx5 in mouse results in cell-autonomous defects in ventricular relaxation. Tbx5 dosage modulates expression of the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2a encoded by Atp2a2 and Tbx5 haploinsufficiency in ventricular myocytes results in impaired Ca2+ uptake dynamics and Ca2+ transient prolongation. We also demonstrate that Tbx5 can activate the Atp2a2 promoter. Furthermore, we find that patients with HOS have significant diastolic filling abnormalities. These results reveal a direct genetic pathway that regulates cardiac diastolic function, implying that patients with structural CHDs may have clinically important underlying anomalies in heart function that merit treatment. [ABSTRACT FROM AUTHOR]

The article discusses the various situations in which pulmonary regurgitation occurs, including repaired Tetralogy of Fallot. It has been found that many patients with right ventricle to pulmonary artery conduit will develop a combination of obstruction and regurgitation across the conduit. Valvar pulmonary stenosis treated with balloon dilatation or surgery can lead to significant pulmonary regurgitation that requires valve replacement.

The physiopathology of right ventricular failure after repair of tetralogy of Fallot is complex. While primarily reflecting chronic volume overload resulting from pulmonary regurgitation, its determinants reflect a varied contribution of different boundary conditions. The competence of the outflow tract, right ventricular afterload, and the integrity of right ventricular diastolic performance are all crucial elements to the long-term responses of the right ventricle. When adverse, chronic right ventricular volume overload may lead to exercise intolerance, congestive cardiac failure, and both atrial and ventricular arrhythmia. Indeed, there appears to be a close relationship between the mechanical properties of the right ventricle and its electrical stability. In this chapter the determinants of pulmonary incompetence and its secondary effects on right ventricular function and performance, and mechano-electric interactions will be discussed. [Copyright &y& Elsevier]

With increasing follow-up of patients after surgical repair of tetralogy of Fallot, the long-term complications of chronic pulmonary regurgitation (PR), ventricular dilation, electrical inhomogeneity and myocardial scarring are becoming apparent. In this article we review the existing literature regarding the deleterious effects of chronic PR in these patients and the current data regarding the timing and mode of intervention. [Copyright &y& Elsevier]

An introduction is presented in which the editor discusses various reports within the issue on topics including the role of valsartan in systemic right ventricle (RV) patients, congential heart disease and heart failure management.

Objective The mechanisms underlying adverse electro-mechanical interaction after tetralogy of Fallot (TOF) repair remain unclear. This study investigated biventricular dyssynchrony in children with TOF and its relationship to exercise, QRS duration (QRSd) and ventricular mechanics. Methods 29 asymptomatic children (5-18⇔…years) with repaired TOF were prospectively evaluated by MRI, cardiopulmonary exercise testing and echocardiography at rest and during bicycle exertion. Their dyssynchrony results were compared with those of 44 resting and 27 exercising, age- and sex-matched controls. An intraventricular dyssynchrony index was calculated from the SD of regional time intervals in 12 left ventricular (LV) 'Ts LV-12SD⇔(tm) and eight right ventricular (RV) 'Ts RV-8SD⇔(tm) segments. Ventricular size, volumes, ejection fractions, pulmonary regurgitant volumes and peak oxygen consumption and N-terminal BNP levels were quantified in the patients. Results Despite moderate RV dilatation (median indexed RV end-diastolic volume 145.2⇔…ml/m2) and right bundle branch block (median QRSd 130⇔…ms) compared with controls, children with TOF demonstrated neither RV nor LV dyssynchrony at rest (Ts RV-8SD, 37.9±10.2 vs 44.3±10.3, 95% CI ⇔'11.8 to ⇔'0.99, p=0.02; Ts LV-12SD, 38.6±16.8 vs 34.0±10.8, 95% CI ⇔'1.8 to 11.0, p=0.16). Exercise stress induced biventricular dyssynchrony in patients with TOF but not in controls (Ts RV-8SD, 59.9±34.4 vs 28.2±10.4, p<0.0001, 95% CI 17.2 to 46.3; Ts LV-12SD, 48.0±18.6 vs 31.9±10.7, 95% CI 7.9 to 24.4, p=0.002). This was unrelated to QRSd, ventricular volumes and function, or peak oxygen consumption. Conclusion Exercise induces biventricular mechanical dyssynchrony in children with TOF. [ABSTRACT FROM AUTHOR]

Recent studies have shown markedly reduced functional capacity in long-term survivors of ventricular septal defect (VSD), and in order to explore possible mechanisms, we performed non-invasive assessment of ventricular force–frequency relationships during exercise in adults operated for VSD in early childhood. We conducted a prospective study at a tertiary referral center. Patients (n = 23) and healthy controls (n = 20) underwent continuous Doppler-echocardiographic imaging during supine bicycle ergometry. The cycling workload was individually and manually incremented during the test session in response to heart rate. The heart was imaged in an apical 4-chamber view, and color-coded myocardial velocities were recorded. Post hoc, peak systolic velocity and isovolumetric acceleration (IVA) were blindly determined in the basal ventricular segments. VSD-operated patients differed markedly in all right ventricular endpoints compared with controls. IVA was lower prior to the test, 70 ± 30 cm/s² vs. 150 ± 60 cm/s² among controls, and during the entire test session ending at a heart rate of 160 beats/min; 140 ± 50 cm/s² vs. 300 ± 30 cm/s², p < 0.01 at both points. A similar pattern was revealed in terms of peak right ventricular systolic velocity. Left ventricular and septal measurements showed a similar, although less significant, tendency with a clearly lower left ventricular optimum heart rate among patients: 140 beats/min vs. 154 beats/min among controls. In the diseased cohort biventricular force–frequency relationships were directly correlated to peak oxygen uptake. VSD repair in early childhood is associated with disruption of the right ventricular force–frequency relationship, which may contribute to the previously observed reduction in functional capacity. [ABSTRACT FROM AUTHOR]

Abstract Background Adult patients with small, unrepaired atrial septal defects (ASD) have higher late mortality than the background population. In this nationwide study, we characterize the late natural history of adults with small, unrepaired ASD. Methods Using the Danish National Patient Registry, we included all Danish patients, diagnosed between 1953 and 2011 with an unrepaired ASD. Additionally, all patients, aged 18–65, were invited for clinical testing. Patients also completed a general health survey for comparison with the general population. Results We identified 723 patients with a small unrepaired ASD. Since the time of diagnosis, 182 patients had died, with an average lifespan of 63 years. The most common cause of death was heart failure. Furthermore, ASD patients had a higher burden of chronic disease than the general population (38.2% vs. 26.9%; p = 0.005), particularly lung disease (3.6% vs. 0.9%; p = 0.008). A total of 153 patients (mean age 32 y) underwent additional testing. On echocardiography an open defect was verified in 19.6% (n = 30) of the patients, of which half subsequently underwent intervention. Interestingly, 6-minute walking distance was markedly reduced (p < 0.0001 compared to normative values) no matter whether the defect was open or closed by echocardiography. Finally, 25.5% of the patients often felt stressed or nervous as compared with 16.3% of the general population (p = 0.004). Conclusions Patients with small, unrepaired ASD in adult life have reduced lifespan, more chronic diseases, impaired submaximal exercise capacity, and higher levels of stress than the general population. The current guidelines for intervention and follow-up may need to be reconsidered. Highlights • Patients with small, unrepaired atrial septal defects had an average lifespan of 63 years. • The most common cause of death was heart failure. • Patients had a higher burden of chronic disease than the general population. • 6-Minute walking distance was markedly reduced compared to normative control values. • Approximately 10% of the included cohort needed intervention. [ABSTRACT FROM AUTHOR]

Abstract 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. Highlights • Recent studies have indicated increased pulmonary vascular resistance in patients operated for a ventricular septal defect • Even relatively minor abnormalities of right ventricular function have been associated with abnormalities of HRV • This study shows that adults who had surgical VSD closure in early childhood have impaired heart rate variability • Particularly, patients with complete RBBB have lower heart rate variability [ABSTRACT FROM AUTHOR]

Abstract 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 ± 13% vs. 111 ± 13%), p < 0.001, impaired forced vital capacity, (106 ± 12% vs. 118 ± 13%), p < 0.001, and lower peak expiratory flow, (95 ± 18% vs. 118 ± 19%), p < 0.001, than the control group. Also, the VSD group had a lower alveolar volume than the control group, (92 ± 10% vs. 101 ± 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. Highlights • There is an increasing awareness of alterations in pulmonary function in patients operated for a ventricular septal defect • This study showed that adults who have undergone surgical closure in early childhood have reduced pulmonary function • Also, it showed that the impairments are unaffected by inhalation of salbutamol [ABSTRACT FROM AUTHOR]

Objective Although heart failure (HF) is the leading cause of premature death in adult congenital heart disease (ACHD), little population-specific data exist. This study reports early experience from a dedicated, sub-specialty adult congenital heart disease-heart failure (ACHD-HF) clinic, aiming to identify risk factors for adverse outcome. Methods Between 2012 and 2015, 126 patients (57% male) attended the ACHD-HF clinic. Baseline and follow-up data were analysed and compared across 4 anatomical/physiological subgroups: cyanotic ACHD, Fontan circulation (1V), biventricular circulation with a subaortic right ventricle (2V-RV) and biventricular circulation with a subaortic left ventricle (2V-LV). Predictors of the composite primary outcome: death, transplant or ventricular assist device (VAD) were identified using multivariable Cox proportional hazard models. Results Mean age at first visit was 38 ± 13 years. Patients were grouped as follows: cyanotic ACHD 10%, 1 V 24%, 2V-RV 29% and 2V-LV 37%. During a median follow-up of 1.7 (IQR 0.8–2.9) years, 38 patients (30%) reached the primary outcome. Event-free survival was 89%, 78% and 63% at 1, 2 and 3 years. Forty (31.7%) patients experienced 69 HF hospitalisations. Between-group differences were noted for systolic function, valvular regurgitation, pacing prevalence and invasive hemodynamics. Multivariable analysis revealed 2V-RV subgroup ( p = 0.001), NYHA class ( p = 0.002) B-type natriuretic peptide > 164 pg/ml ( p = 0.003) and sodium < 136 mmol/L ( p = 0.036) as independently associated with death, transplant or VAD. Conclusions Our young ACHD-HF patients experienced high adverse event rates during a short period of follow-up. The prognostic markers identified will aid clinicians to stratify short-term risk and thereby guide advanced HF management decisions in ACHD. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of our study was to characterize the hemodynamic and corresponding pharmacokinetic responses to a single dose of oral sildenafil by children with pulmonary arterial hypertension (PAH) undergoing invasive testing. Background: Although used frequently for the treatment of children with PAH, data regarding the acute responses to sildenafil are limited. Methods: Thirty-six patients (mean age 7.5 ± 5.9 years; 24 females) were studied during cardiac catheterization with general anesthesia. Eight of 36 (22%) had idiopathic PAH; the remainder had associated congenital heart disease. Hemodynamics and serum cyclic-guanosine monophosphate levels (cGMP) were evaluated at baseline and after inhaled nitric oxide (NO) (40 ppm). In addition, cGMP and sildenafil levels were measured 30 min after administration of sildenafil (0.5 mg/kg, suspended in 5 ml sterile water) through a nasogastric tube. Results: For the 36 patients, the pulmonary vasodilating capability of oral sildenafil was lower than that of inhaled NO (2.8% vs. 11.6% reduction in pulmonary vascular resistance indexed to body surface area [PVRI], respectively; p = 0.01). However, only 21 of 36 (58%) patients had a detectable sildenafil level. In those with detectable sildenafil levels, the fall in PVRI was greater (−11.6% vs. −19.1%, p = NS). Mean cGMP levels at baseline and after NO were 41.8 ± 20.0 pmol/ml and 83.8 ± 35.5 pmol/ml, respectively (p < 0.0001). Surprisingly, there was no significant increase in cGMP in patients with either undetectable (37.5 ± 29.8 pmol/ml) or detectable (44.4 ± 31.7 pmol/ml) sildenafil levels (p = NS compared with baseline) with sildenafil. Conclusions: Our study demonstrates suboptimal absorption of sildenafil in almost half the children undergoing acute hemodynamic testing. When detectable, there was no statistically significant difference between the fall in PVRI associated with sildenafil and NO despite lower circulating cGMP levels in the sildenafil group. These data should be taken into account when designing acute testing protocols, and assessing the acute response to sildenafil in patients with PAH. [Copyright &y& Elsevier]

Abstract: Objective: The arterial-switch operation (ASO) for management of Taussig–Bing anomaly is associated with important morbidity, mainly related to multiple associated cardiac anomalies. Our surgical management has evolved to suggest a single-stage total repair strategy tailored to address all abnormalities on an individual basis. We examine the efficacy of this treatment approach. Methods: Thirty-three children, (infants n =29), with Taussig–Bing underwent ASO (1979–2005). In our earlier experience (group 1, n =17), initial palliation was performed as needed, including pulmonary–artery banding (n =9), coarctation repair (n =6), and atrial septostomy (n =3) followed by ASO at a later age. In our later experience (group 2, n =16), single-stage total repair was performed; ASO with ventricular septal defect closure and baffling of left ventricle to neo-aorta performed in neonates with arch obstruction (n =8), or at age 6 weeks in those with no arch obstruction (n =8). Concomitant relief of right-ventricle outflow-tract obstruction (RVOTO) was performed in 14 patients. Demographics and operative variables affecting outcomes were analyzed. Results: Mean age at operation for group 1 and 2 patients was 312±477 and 42±31 days (p <0.0001). Aortic arch obstruction (52%), sub-aortic RVOTO (61%) and unusual coronary patterns (52%) were similar for both groups. One-year survival for group 1 and 2 patients was 47±5% and 100% (p =0.001). Associated anomalies such as great vessels position, arch obstruction, and unusual coronaries were not significant risk factors for mortality on multivariable analysis. Ten-year freedom from RVOT and arch re-operation was 55±5% and 96±4%. Five-year event-free survival for groups 1 and 2 was 35±6% and 87±1% (p =0.0016). Significant factors affecting event-free survival were group 1 (HR 108, p =0.0005), and larger weight at surgery (HR 1.3, p =0.02). Conclusions: The Taussig–Bing anomaly is complex and often associated with other cardiac anomalies (arch obstruction, RVOTO, unusual coronary pattern). Advances in perioperative care have significantly mitigated mortality. In our experience with single-stage total repair, event-free survival, especially freedom from RVOT re-operation, has significantly improved. [Copyright &y& Elsevier]

Introduction: Diastolic dysfunction is increasingly recognized as a contributor to failing Fontan circulation. The relationship between invasive hemodynamics (IHD) and diffuse myocardial fibrosis (DMF) has not been investigated. Methods: Prospective observational study of outpatient adolescents and young adults with Fontan circulation. Resting and rapid volume expansion (stress) IHD were obtained via clinically indicated cardiac catheterization. Cardiac magnetic resonance imaging was obtained for characterization of DMF using T1 mapping to estimate extracellular volume fraction (ECV), which was the primary outcome. Determinants included resting and stress IHD variables, including cardiac index (CI), pulmonary artery pressure (PAP) and end diastolic pressure (EDP) as well as non-IHD patient factors. Associations between ECV and IHD variables were assessed by Spearman correlation. Subjects were grouped as DMF+ (ECV≥27%) or DMF- (ECV <27%), with differences assessed by Wilcoxon rank sum. Results: The study cohort included 22 Fontan patients (45% female) with median age 17.5 yrs (IQR 12.6, 23.4) and Fontan duration 14.5 yrs (7.9, 20.9). Single ventricle (SV) morphology was left in 68%. Fontan type was extracardiac (50%) and lateral tunnel (45%). Median resting PAP and EDP were 12 mmHg (10, 13) and 8 mmHg (8, 10), while stress PAP and EDP were 14.5 mmHg (14, 15) and 12 mmHg (11, 14), respectively. Median ECV was 28% (25, 30) with ECV≥27% in 59% of the cohort. Both resting (r=0.45, p=0.04) and stress (r=0.51, p=0.02) PAP were strongly associated with ECV%. Resting EDP trended towards an association (r=0.37, p=0.09), whereas no other IHD measures did so. In subgroup analysis, resting PAP trended higher (12.8 vs 10.7 mmHg, p=0.06) and stress PAP was significantly higher (15.9 vs 13.7 mmHg, p=0.05) in the DMF+ group. No other IHD variables, nor age, duration of Fontan, Fontan type or SV morphology, differed significantly by DMF group. Conclusions: In adolescent and young adult Fontan patients, higher resting and stress PAP, but not CI, SV morphology or duration of Fontan circulation, identifies patients at risk for subclinical DMF. Such findings suggest that DMF might serve as an imaging biomarker of Fontan circulatory dysfunction, and thus, a therapeutic target to improve Fontan physiology. [ABSTRACT FROM AUTHOR]