Single-Molecule Analysis Reveals Linked Cycles of RSC Chromatin Remodeling and Ace1p Transcription Factor Binding in Yeast.

It is unknown how the dynamic binding of transcription factors (TFs) is molecularly linked to chromatin remodeling and transcription. Using single-molecule tracking (SMT), we show that the chromatin remodeler RSC speeds up the search process of the TF Ace1p for its response elements (REs) at the CUP1 promoter. We quantified smFISH mRNA data using a gene bursting model and demonstrated that RSC regulates transcription bursts of CUP1 only by modulating TF occupancy but does not affect initiation and elongation rates. We show by SMT that RSC binds to activated promoters transiently, and based on MNase-seq data, that RSC does not affect the nucleosomal occupancy at CUP1. Therefore, transient binding of Ace1p and rapid bursts of transcription at CUP1 may be dependent on short repetitive cycles of nucleosome mobilization. This type of regulation reduces the transcriptional noise and ensures a homogeneous response of the cell population to heavy metal stress.

Adults With Congenital Heart Disease: Trends in Event-Free Survival Past Middle Age.

BACKGROUND: The survival of children with congenital heart disease has increased substantially over the past decades, with 97% currently reaching adulthood. The total effect of advanced treatment on future mortality and morbidity in adult survivors with congenital heart disease (CHD) is less well described. METHODS: We used data from the Swedish National Inpatient, Outpatient, and Cause of Death Register to identify patients with CHD who were born between 1950 and 1999 and were alive at 18 years of age. Ten controls identified from the Total Population Register were matched for year of birth and sex and with each patient with CHD. Follow-up was from 1968 and 18 years of age until death or at the end of the study (2017). Survival percentage with 95% CI for all-cause mortality were performed with Kaplan-Meier survival function. Cox proportional hazard regression models with hazard ratios (HRs) and 95% CI were used to estimate the risk of all-cause mortality. RESULTS: We included 37 278 patients with adult CHD (ACHD) and 412 799 controls. Mean follow-up was 19.2 years (±13.6). Altogether, 1937 patients with ACHD (5.2%) and 6690 controls (1.6%) died, a death rate of 2.73 per 1000 person-years and 0.84 per 1000 person years, respectively. Mortality was 3.2 times higher (95% CI, 3.0-3.4; P<0.001) among patients with ACHD compared with matched controls. Up to the maximum of 50 years of follow-up, >75% of patients with ACHD were still alive. Mortality was highest among patients with conotruncal defects (HR, 10.13 [95% CI, 8.78-11.69]), but also significantly higher for the more benign lesions, with the lowest risk in patients with atrial septal defects (HR, 1.36 [95% CI, 1.19-1.55]). At least 75% of patients with ACHD alive at 18 years of age lived past middle age and became sexagenerians. CONCLUSIONS: In this large, nationwide, register-based cohort study of patients with ACHD surviving to 18 years of age, the risk of mortality up to 68 years of age was >3 times higher compared with matched controls without ACHD. Despite this, at least 75% of patients with CHD alive at 18 years of age lived past middle age and became sexagenerians. A notable risk decline in the mortality for patients with ACHD was seen for those born after 1975.

Percutaneous atrial shunt closure and the risk of recurrent ischemic stroke: A register-based, nationwide cohort study.

OBJECTIVES: We aimed to investigate the risk of recurrent stroke in patients with transcatheter closure of an atrial shunt (ASCIos), compared to patients with an atrial shunt and cerebrovascular event (CVE) but only medical treated (ASMed), and to age- and sex-matched control individuals without a previous CVE. METHODS: In total, 663 ASCIos patients were identified in the Swedish National Patient Register from 1997 to 2016 and matched by using propensity score with 663 ASMed patients. Nine age- and sex-matched controls to ASCIos patients (n = 6,302) without a diagnosis of atrial shunt or history of CVE were randomly selected from the general population. RESULTS: At a mean follow-up of 6.5 years, the incidence rate of recurrent stroke in the ASCIos group vs ASMed group was 0.9 vs 0.7 per 100 patient-years. The hazard ratio of recurrent stroke in the ASCIos group compared with index stroke in the control group was 9.9 (95% confidence interval, 5.5-17.9). The incidence of atrial fibrillation was similar in the ASCIos and the ASMed group, however four times higher in the ASCIos than in the control group. CONCLUSIONS: Our large nationwide, register-based cohort study showed that, unexpectedly, the risk of recurrent stroke in the ASCos group was as high as in the ASMed group and almost ten times higher than the risk of an index stroke in matched controls without previous stroke.

Contrasting roles of the RSC and ISW1/CHD1 chromatin remodelers in RNA polymerase II elongation and termination.

Most yeast genes have a nucleosome-depleted region (NDR) at the promoter and an array of regularly spaced nucleosomes phased relative to the transcription start site. We have examined the interplay between RSC (a conserved essential SWI/SNF-type complex that determines NDR size) and the ISW1, CHD1, and ISW2 nucleosome spacing enzymes in chromatin organization and transcription, using isogenic strains lacking all combinations of these enzymes. The contributions of these remodelers to chromatin organization are largely combinatorial, distinct, and nonredundant, supporting a model in which the +1 nucleosome is positioned by RSC and then used as a reference nucleosome by the spacing enzymes. Defective chromatin organization correlates with altered RNA polymerase II (Pol II) distribution. RSC-depleted cells exhibit low levels of elongating Pol II and high levels of terminating Pol II, consistent with defects in both termination and initiation, suggesting that RSC facilitates both. Cells lacking both ISW1 and CHD1 show the opposite Pol II distribution, suggesting elongation and termination defects. These cells have extremely disrupted chromatin, with high levels of closely packed dinucleosomes involving the second (+2) nucleosome. We propose that ISW1 and CHD1 facilitate Pol II elongation by separating closely packed nucleosomes.

Accessibility of promoter DNA is not the primary determinant of chromatin-mediated gene regulation.

DNA accessibility is thought to be of major importance in regulating gene expression. We test this hypothesis using a restriction enzyme as a probe of chromatin structure and as a proxy for transcription factors. We measured the digestion rate and the fraction of accessible DNA at almost all genomic AluI sites in budding yeast and mouse liver nuclei. Hepatocyte DNA is more accessible than yeast DNA, consistent with longer linkers between nucleosomes, suggesting that nucleosome spacing is a major determinant of accessibility. DNA accessibility varies from cell to cell, such that essentially no sites are accessible or inaccessible in every cell. AluI sites in inactive mouse promoters are accessible in some cells, implying that transcription factors could bind without activating the gene. Euchromatin and heterochromatin have very similar accessibilities, suggesting that transcription factors can penetrate heterochromatin. Thus, DNA accessibility is not likely to be the primary determinant of gene regulation.

Long-term outcomes after myocardial infarction in middle-aged and older patients with congenital heart disease-a nationwide study.

AIMS: We aimed to describe the risk of myocardial infarction (MI) in middle-aged and older patients with congenital heart disease (ACHD) and to evaluate the long-term outcomes after index MI in patients with ACHD compared with controls. METHODS AND RESULTS: A search of the Swedish National Patient Register identified 17 189 patients with ACHD (52.2% male) and 180 131 age- and sex-matched controls randomly selected from the general population who were born from 1930 to 1970 and were alive at 40 years of age; all followed up until December 2017 (mean follow-up 23.2 ± 11.0 years). Patients with ACHD had a 1.6-fold higher risk of MI compared with controls [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.5-1.7, P < 0.001] and the cumulative incidence of MI by 65 years of age was 7.4% in patients with ACHD vs. 4.4% in controls. Patients with ACHD had a 1.4-fold increased risk of experiencing a composite event after the index MI compared with controls (HR 1.4, 95% CI 1.3-1.6, P < 0.001), driven largely by the occurrence of new-onset heart failure in 42.2% (n = 537) of patients with ACHD vs. 29.5% (n = 2526) of controls. CONCLUSION: Patients with ACHD had an increased risk of developing MI and of recurrent MI, new-onset heart failure, or death after the index MI, compared with controls, mainly because of a higher incidence of newly diagnosed heart failure in patients with ACHD. Recognizing and managing the modifiable cardiovascular risk factors should be of importance to reduce morbidity and mortality in patients with ACHD.

Outcome and survival after open heart surgery for adults with congenital heart disease - a single center experience.

Introduction. Congenital heart disease (CHD) is the most common type of birth defect today. The adult congenital heart disease (ACHD) population is constantly growing and becoming older and more patients require cardiac surgery. The objective of this study was to review the surgical outcome of the open heart procedures performed on ACHD patients in the last 10 years at Sahlgrenska University Hospital (SUH) through a retrospective descriptive cohort study. Methods. A retrospective data collection was performed for 421 patients who underwent a total of 439 surgical procedures between 2009 and 2018 at the Cardiothoracic department in SUH. The primary outcomes were early (<30 days) and late survival. Secondary outcomes were postoperative complications and independent risk factors for postoperative complications. Results. 30-day mortality was 1.9%. Long-term survival after 3, 5 and 10 years were 96% ± 1, 94.3% ± 1.3 and 92.4% ± 1.8. 82 major complications occurred after 46 procedures (11.6%). The most common major complication was re-exploration due to hemorrhage. Risk factors for major complications were acute surgery and prolonged extracorporeal circulation time. 173 minor complications occurred after 90 procedures (22.5%). The most common minor complication was prolonged intensive care unit stay (>48 h). Conclusion. This study presents satisfactory early and midterm survival. The survival and frequency of major postoperative complications are well in line with what other studies have presented. Patients undergoing resternotomies had no increased risk for mortality or postoperative complications.

Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

BACKGROUND: The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS: In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. RESULTS: A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). CONCLUSIONS: Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).

Cardiac Complications during Pregnancy Related to Parity in Women with Congenital Heart Disease.

OBJECTIVE: To describe the frequency of cardiac complications during pregnancy related to parity in women with congenital heart defects. METHODS: A retrospective tertiary single-center study at the Adult Congenital Heart Disease Centre that followed 307 women with congenital heart disease during the years 1997-2015 in Gothenburg, Sweden. Ma-ternal cardiac complications were noted for each pregnancy using medical and obstetric records. The CARPREG I and modified WHO (mWHO) risk classifications were used. Twin pregnancies, miscarriages before gestational week 13, and pregnancy terminations were excluded. RESULTS: Five hundred seventy-one deliveries and 9 late miscarriages were analyzed. The mean parity was 1.74 per woman (range 1-8). Eighty-four (14.6%) maternal cardiac complications were experienced; arrhythmia (5.7%) and heart failure (4.4%) being the most prevalent, and there was 1 maternal death. Heart failure occurred during the first pregnancy in 12 women (3.9%), in the second pregnancy in 8 women (4.3%), and in the third pregnancy in 4 women (7.7%). CARPREG I and mWHO scores were associated with an increased risk of having a cardiac complication, while parity per se was not associated. The OR for having a maternally uneventful second pregnancy if the first pregnancy was without cardiac complications was 5.47 (95% CI 1.76-16.94) after controlling for CARPREG I and mWHO scores. CONCLUSION: The risk of severe maternal cardiac complications during pregnancy in women with congenital heart disease is low. In this largest analysis to date with a focus on parity in 307 women, the risk classification predicts the maternal outcome more than parity per se. If the first pregnancy is uneventful, the OR is 5.5 for an uneventful second pregnancy if CARPREG I and mWHO scores remain unchanged.

Validation of myocardial infarction diagnosis in patients with congenital heart disease in Sweden.

BACKGROUND: The population of adults with congenital heart disease (CHD) is growing, and increasingly more patients with CHD reach older ages. Patients with CHD are at an increased risk of myocardial infarction (MI) with increased age. Diagnosing MI in patients with CHD can be challenging in clinical practice owing to a high prevalence of aberrant electrocardiograms, ventricular hypertrophy, and heart failure, among other factors. The National Swedish Patient Register (NPR) is widely used in epidemiological studies; however, MI diagnoses specifically in patients with CHD have never been validated in the NPR. METHODS: We contacted hospitals and medical archive services to request medical records for 249 patients, born during 1970-2012, with both CHD and MI diagnoses and who were randomly selected from the NPR by the Swedish National Board of Health and Welfare. Follow-up was until 2015. We performed a medical chart review to validate the MI diagnoses; we also validated CHD diagnoses to ensure that only patients with confirmed CHD diagnoses were included in the MI validation process. RESULTS: We received medical records for 96.4% (n = 238/249) of patients for validation of CHD diagnoses. In total, 74.8% (n = 178/238) had a confirmed CHD diagnosis; of these, 70.2% (n = 167) had a fully correct CHD diagnosis in the NPR; a further 4.6% (n = 11) had a CHD diagnosis, but it was misclassified. MI diagnoses were validated in 167 (93.8%) patients with confirmed CHD. Of the patients with confirmed CHD, 88.0% (n = 147/167) had correct MI diagnoses. Patients with non-complex CHD diagnoses had more correct MI diagnoses than patients with complex CHD (91.0%, n = 131 compared with 69.6%, n = 16). The main cause for incorrect MI diagnoses was typographical error, contributing to 50.0% of the incorrect diagnoses. CONCLUSIONS: The validity of MI diagnoses in patients with confirmed CHD in the NPR is high, with nearly 9 of 10 MI diagnoses being correct (88.0%). MI in patients with CHD can safely be studied using the NPR.

Exercise capacity, physical activity, and health-related quality of life in adults with CHD.

OBJECTIVES: The aim of this study was to assess exercise capacity, physical activity, and health-related quality of life within a broad and unselected group of adults with CHD. DESIGN: From April 2009 to February 2014, 1310 patients were assessed for suitability to participate in this single-centre cross-sectional study. Seven hundred and forty-seven (57%) patients were included, performed a submaximal bicycle test, and answered questionnaires regarding physical activity and health-related quality of life. Exercise capacity, physical activity, and health-related quality of life were compared with reference values and correlations were studied. RESULTS: The exercise capacities of men and women with CHD were 58.7 and 66.3%, respectively, of reference values. Approximately, 20-25% of the patients did not achieve the recommended amount of physical activity. In addition, men scored significantly less points on 7 out of 10 scales of health-related quality of life and women in 6 out of 10 scales, compared with reference values. The strongest correlation was between exercise capacity and the Short Form-36 (physical function). CONCLUSIONS: Exercise capacity was impaired in all adults with CHD, including those with less complicated CHD. One-quarter of the patients did not achieve the recommended levels of physical activity. Exercise tests followed by individualised exercise prescriptions may be offered to all patients with CHD aiming to increase exercise capacity, levels of physical activity, improve health-related quality of life, and reduce the risk of acquired life-style diseases.

Recurrent cerebrovascular events in patients after percutaneous closure of patent foramen ovale.

BACKGROUND: Recent published trials have shown the efficacy of transcatheter closure of patent foramen ovale (PFO) for preventing recurrent cryptogenic cerebrovascular events. However, the risk of recurrent cerebrovascular events (rCVEs) is up to 5.7%, and the etiology is unclear. OBJECTIVE: This study aimed to investigate the risk factors for rCVEs after closure of PFO during long-term follow-up. METHODS: In our center, 282 consecutive patients underwent PFO closure because of a cryptogenic cerebrovascular event between 2006 and 2014. Their Risk of Paradoxical Embolism (RoPE) score was calculated retrospectively. We followed up with the patients by telephone, using hospital records to identify those who suffered from rCVEs. Patients with rCVEs were matched with two control patients of the same sex and RoPE score without rCVEs who underwent PFO closure at approximately the same time. The patients with rCVEs and controls participated in a clinical examination, including contrast transthoracic echocardiography (TTE) and Holter electrocardiography, to investigate the possible cause of rCVEs compared with controls. RESULTS: Fourteen (5%) out of the 282 consecutive patients who underwent PFO closure suffered from rCVEs during a mean follow-up of 8.4 years (1.7 rCVEs per 100 patient-years). The median RoPE score of the patients was 7. Recurrent CVE occurred in 3.2 patients per 100 patient-years in patients with residual shunting compared with 0.8 patients per 100 patient-years in those without residual shunt. These patients were on antiplatelet treatment or without any effective anticoagulant treatment at the time rCVE occurred. The risk ratio of rCVEs in patients with residual shunting was 2.9-times higher than in patients without residual shunting (95% CI: 1.4-6.1) at follow-up visit. Four patients who had the BioSTAR device implanted suffered from an rCVE despite lack of residual shunting. CONCLUSIONS: This study indicates that residual shunting and choice of the device may be the major reasons for rCVEs.

Atrial Fibrillation Burden in Young Patients With Congenital Heart Disease.

BACKGROUND: Patients with congenital heart disease (CHD) are assumed to be vulnerable to atrial fibrillation (AF) as a result of residual shunts, anomalous vessel anatomy, progressive valvulopathy, hypertension, and atrial scars from previous heart surgery. However, the risk of developing AF and the complications associated with AF in children and young adults with CHD have not been compared with those in control subjects. METHODS: Data from the Swedish Patient and Cause of Death registers were used to identify all patients with a diagnosis of CHD who were born from 1970 to 1993. Each patient with CHD was matched by birth year, sex, and county with 10 control subjects from the Total Population Register in Sweden. Follow-up data were collected until 2011. RESULTS: Among 21 982 patients (51.6% men) with CHD and 219 816 matched control subjects, 654 and 328 developed AF, respectively. The mean follow-up was 27 years. The risk of developing AF was 21.99 times higher (95% confidence interval, 19.26-25.12) in patients with CHD than control subjects. According to a hierarchical CHD classification, patients with conotruncal defects had the highest risk (hazard ratio, 84.27; 95% confidence interval, 56.86-124.89). At the age of 42 years, 8.3% of all patients with CHD had a recorded diagnosis of AF. Heart failure was the quantitatively most important complication in patients with CHD and AF, with a 10.7% (70 of 654) recorded diagnosis of heart failure. CONCLUSIONS: The risk of AF in children and young adults with CHD was 22 times higher than that in matched control subjects. Up to the age of 42 years, 1 of 12 patients with CHD had developed AF, and 1 of 10 patients with CHD with AF had developed heart failure. The patient groups with the most complex congenital defects carried the greatest risk of AF and could be considered for targeted monitoring.

Long-Term Risk of Hemorrhagic Stroke in Young Patients With Congenital Heart Disease.

BACKGROUND AND PURPOSE: The risk of ischemic stroke is increased in patients with congenital heart disease (CHD); however, data on the risk of hemorrhagic stroke, including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), are lacking. METHODS: The Swedish Patient Register was used to identify all patients who were born with a diagnosis of CHD between 1970 and 1993. Each patient was compared with 10 randomly selected controls from the general population, matched for age, sex, and county. Follow-up data were collected until December 2011 for both cases and controls. RESULTS: Of 21 982 patients with CHD, 70 developed ICH and 57 developed SAH up to the age of 42 years. CHD patients had more than an 8× higher risk (incidence rate ratio, 8.23; 95% confidence interval, 6-11.2) of developing ICH and almost an 8× higher risk of developing SAH (incidence rate ratio, 7.64; 95% confidence interval, 5.41-10.7) compared with controls. The absolute risk of ICH and SAH was low, with incidence rates of 1.18 and 0.96 cases per 10 000 person-years, respectively. Patients with severe nonconotruncal defects (incidence rate ratio, 16.5; 95% confidence interval, 5.63-51.2) or coarctation of the aorta (incidence rate ratio, 17.3; 95% confidence interval, 6.63-51.8) had the highest relative risk of developing hemorrhagic stroke, with incidence rates of 3.22 and 2.79 cases per 10 000 person-years, respectively. CONCLUSIONS: The relative risk of hemorrhagic stroke among children and young adults with CHD was almost 8× higher than that of matched controls from the general population, although the absolute risk was low. The highest risk of ICH and SAH occurred in patients with severe nonconotruncal defects and coarctation of the aorta.

The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo.

Adenosine triphosphate-dependent chromatin remodeling machines play a central role in gene regulation by manipulating chromatin structure. Most genes have a nucleosome-depleted region at the promoter and an array of regularly spaced nucleosomes phased relative to the transcription start site. In vitro, the three known yeast nucleosome spacing enzymes (CHD1, ISW1 and ISW2) form arrays with different spacing. We used genome-wide nucleosome sequencing to determine whether these enzymes space nucleosomes differently in vivo We find that CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing. In contrast, ISW2 plays a minor role, limited to transcriptionally inactive genes. Heavily transcribed genes show weak phasing and extreme spacing, either very short or very long, and are depleted of linker histone (H1). Genes with longer spacing are enriched in H1, which directs chromatin folding. We propose that CHD1 directs short spacing, resulting in eviction of H1 and chromatin unfolding, whereas ISW1 directs longer spacing, allowing H1 to bind and condense the chromatin. Thus, competition between the two remodelers to set the spacing on each gene may result in a highly dynamic chromatin structure.

Coronary Artery Fistulas: Case Series and Literature Review.

Congenital coronary artery fistulas are rare anomalies. As coronary angiography and multidetector computed tomography have become more accessible, they have been increasingly used in the investigation of chest pain and heart failure. Coronary artery fistulas are often an incidental finding, which raises the question of how patients with this condition should be managed. Intervention with either transcatheter closure or surgical closure is often technically possible. Many patients are asymptomatic early after closure. However, follow-up studies have shown post-closure sequelae, such as residual leakage, thrombosis with or without myocardial infarction, and coronary stenosis. Therefore, there has been a shift from intervention towards watchful waiting in asymptomatic patients. In this article, we review the published literature on the natural history and treatment outcomes in individuals with coronary artery fistulas. We present case reports from our clinic and discuss the management of incidental findings of coronary artery fistulas.

RV to PA conduits: impact of transcatheter pulmonary valve replacement in adults - a national register study.

OBJECTIVE: The use of a conduit is an established surgical method for reconstruction of the right ventricular outflow tract in congenital heart disease; however, its limited durability makes reintervention almost inevitable. We studied the trends in new implantation, reoperation, and transcatheter pulmonary valve replacement (TPVR) from a Swedish national perspective. DESIGN AND RESULTS: The Swedish registry of congenital heart disease (SWEDCON) was used to collect data. From 2000-2014, there was an increase in adult patients with conduits from 122 to 536. There were 60 surgical conduit replacements, 40 TPVRs and 176 new conduit implantations in the study period. Perioperative mortality was <1%. The yearly number of new implantations and reoperations both doubled over the study period. Patients with new implantations were older (mean age, 36 years) compared with the reoperation and TPVR groups (mean age, 26 years) with the majority of patients having tetralogy of Fallot. The majority of conduit reinterventions were surgical also after the introduction of TPVR in 2007, with no significant difference regarding diagnosis, gender, age, or previous number or longevity of conduits. CONCLUSION: The number of adults with conduits increased steadily with most conduit-related operations being new implantations in patients with tetralogy of Fallot. Surgical conduit replacements increased significantly and represented the majority of conduit reinterventions after the introduction of TPVR, indicating that TPVR is not used for the majority of patients with conduit failure. Diagnosis, gender, age, or previous number or longevity of conduits had no impact on choosing surgical replacement vs. TPVR.

Long-term outcome after right ventricle to pulmonary artery conduit surgery and reintervention.

BACKGROUND: Reconstruction of the right ventricular outflow tract with a conduit is an established surgical procedure in congenital heart disease and reinterventions are common. OBJECTIVE: An increasing number of patients have a conduit, but there are few population-based studies of long-term outcomes after conduit surgery, reoperations, and transcatheter pulmonary valve replacement. METHODS: In April 2015, all adult patients with a conduit were identified in the Swedish National Registry for Congenital Heart Disease (SWEDCON). Data on patients who died before age of 16 years are not included in the registry and thus not included in the study. RESULTS: We found 574 patients with a mean age 36.1 years. The largest proportion had tetralogy of Fallot (45%). In total there were 762 operations and 50 transcatheter pulmonary valve replacements. Mean age at first conduit operation was 20.2 years. Long-term survival up to 48 years including perioperative mortality (<1%) was 93% at 20 years. The most common cause of death was cardiac-related. Higher age at first conduit operation was associated with increased mortality risk. Reintervention-free survival was 77% and 54% at 10 and 20 years, respectively. Conduit reinterventions were common. Ten-year reintervention-free survival after first conduit reintervention (n = 176) was significantly lower than after first conduit operation (70% vs 77% p = .04). Higher age at first conduit operation was associated with a reduced risk of reintervention, whereas male sex and complex malformations were associated with increased risk of reintervention. CONCLUSIONS: The mortality of repeated conduit reinterventions is low. The need for reintervention of conduits is considerable, and reintervention-free survival after the first conduit reintervention is poorer than after first conduit implantation. The findings in this study only applies for patients reaching 16 years of age.

Type 1 diabetes mellitus and associated risk factors in patients with or without CHD: a case-control study.

BACKGROUND: Approximately 1% of children are born with CHD, and 90-95% reach adulthood. Increased exposure to infections and stress-strain can contribute to an increased risk of developing type 1 diabetes mellitus. CHD may increase the risk of more serious infections, stress-strain, and increased risk of developing type 1 diabetes mellitus. METHODS: We analysed the onset of and the risk of mortality and morbidity associated with concurrent CHD in patients with type 1 diabetes mellitus compared with patients with type 1 diabetes mellitus without CHD. The study combined data from the National Diabetes Register and the National Patient Register. RESULTS: A total of 104 patients with CHD and type 1 diabetes mellitus were matched with 520 controls. Patients with CHD and type 1 diabetes mellitus had an earlier onset of diabetes (13.9 versus 17.4 years, p<0.001), longer duration of diabetes (22.4 versus 18.1 years, p<0.001), higher prevalence of retinopathy (64.0 versus 43.0%, p=0.003), higher creatinine levels (83.5 versus 74.1 µmol/L, p=0.03), higher mortality (16 versus 5%, p=0.002), and after onset of type 1 diabetes mellitus higher rates of co-morbidity (5.28 versus 3.18, p⩽0.01), heart failure (9 versus 2%, p=0.02), and stroke (6 versus 2%, p=0.048) compared with controls. CONCLUSIONS: From a nationwide register of patients with type 1 diabetes mellitus, the coexistence of CHD and type 1 diabetes mellitus was associated with an earlier onset, a higher frequency of microvascular complications, co-morbidity, and mortality.