The Fontan procedure is the final stage of surgical palliation for a single-ventricle circulation. Significant complications are common including rhythm disturbance necessitating implantation of a ...permanent pacemaker. This has been widely considered a negative prognostic indicator.
This single-centre, retrospective case control study involved all patients who underwent the Fontan procedure at the Leeds Congenital Heart Unit between 1990 and 2015 and have had regular follow-up in Yorkshire and Humber, United Kingdom. 167 Fontan patients were identified of which 2 were excluded for having a pre-procedure pacemaker. Of the remainder, 23 patients required a pacemaker. Outcomes were survival, early and late complications, need for further intervention and oxygen saturation in long-term follow-up.
There was no difference in survival (30-day survival pacemaker 92.6%, sinus rhythm 90.5%, p = 0.66, 1-year pacemaker 11.1%, sinus rhythm 10.1%, p = 1). The pacemaker group was more likely to have cerebral or renal complications in the first-year post-procedure (acute kidney injury: sinus rhythm 0.8%, pacemaker 19.1%, p = 0.002). No difference was observed in longer term complications including protein losing enteropathy (sinus rhythm 3.5%, pacemaker 0% p = 1). There was no difference in saturations between the two groups at follow-up. Paced patients were more likely to have required further intervention, with a higher incidence of cardiopulmonary bypass procedures (sinus rhythm 6.3%, pacemaker 35%, p < 0.001).
Despite an increase in early complications and the need for further interventions, pacemaker requirement does not appear to affect long-term survival following the Fontan procedure.
Neurofibromatosis 2 (NF2) is an autosomal-dominant tumour predisposition syndrome characterised by bilateral vestibular schwannomas, considerable morbidity and reduced life expectancy. Although ...genotype-phenotype correlations are well established in NF2, little is known about effects of mutation type or location within the gene on mortality. Improvements in NF2 diagnosis and management have occurred, but their effect on patient survival is unknown.
We evaluated clinical and molecular predictors of mortality in 1192 patients (771 with known causal mutations) identified through the UK National NF2 Registry. Kaplan-Meier survival and Cox regression analyses were used to evaluate predictors of mortality, with jackknife adjustment of parameter SEs to account for the strong intrafamilial phenotypic correlations that occur in NF2.
The study included 241 deaths during 10 995 patient-years of follow-up since diagnosis. Early age at diagnosis and the presence of intracranial meningiomas were associated with increased mortality, and having a mosaic, rather than non-mosaic, NF2 mutation was associated with reduced mortality. Patients with splice-site or missense mutations had lower mortality than patients with truncating mutations (OR 0.459, 95% CI 0.213 to 0.990, and OR 0.196, 95% CI 0.213 to 0.990, respectively). Patients with splice-site mutations in exons 6-15 had lower mortality than patients with splice-site mutations in exons 1-5 (OR 0.333, 95% CI 0.129 to 0.858). The mortality of patients with NF2 diagnosed in more recent decades was lower than that of patients diagnosed earlier.
Continuing advances in molecular diagnosis, imaging and treatment of NF2-associated tumours offer hope for even better survival in the future.
BACKGROUND Primary pulmonary hypertension (PPH), resulting from occlusion of small pulmonary arteries, is a devastating condition. Mutations of the bone morphogenetic protein receptor type II gene ...(BMPR2), a component of the transforming growth factor beta (TGF-β) family which plays a key role in cell growth, have recently been identified as causing familial PPH. We have searched for BMPR2 gene mutations in sporadic PPH patients to determine whether the same genetic defect underlies the more common form of the disorder. METHODS We investigated 50 unrelated patients, with a clinical diagnosis of PPH and no identifiable family history of pulmonary hypertension, by direct sequencing of the entire coding region and intron/exon boundaries of the BMPR2 gene. DNA from available parent pairs (n=5) was used to assess the occurrence of spontaneous (de novo) mutations contributing to sporadic PPH. RESULTS We found a total of 11 different heterozygous germline mutations of theBMPR2 gene in 13 of the 50 PPH patients studied, including missense (n=3), nonsense (n=3), and frameshift (n=5) mutations each predicted to alter the cell signalling response to specific ligands. Parental analysis showed three occurrences of paternal transmission and two of de novo mutation of theBMPR2 gene in sporadic PPH. CONCLUSION The sporadic form of PPH is associated with germline mutations of the gene encoding the receptor protein BMPR-II in at least 26% of cases. A molecular classification of PPH, based upon the presence or absence ofBMPR2 mutations, has important implications for patient management and screening of relatives.
Primary pulmonary hypertension (PPH) is a potentially lethal disorder, because the elevation of the pulmonary arterial pressure may result in right-heart failure. Histologically, the disorder is ...characterized by proliferation of pulmonary-artery smooth muscle and endothelial cells, by intimal hyperplasia, and by in situ thrombus formation. Heterozygous mutations within the bone morphogenetic protein type II receptor (BMPR-II) gene (
BMPR2), of the transforming growth factor β (TGF-β) cell–signaling superfamily, have been identified in familial and sporadic cases of PPH. We report the molecular spectrum of
BMPR2 mutations in 47 additional families with PPH and in three patients with sporadic PPH. Among the cohort of patients, we have identified 22 novel mutations, including 4 partial deletions, distributed throughout the
BMPR2 gene. The majority (58%) of mutations are predicted to lead to a premature termination codon. We have also investigated the functional impact and genotype-phenotype relationships, to elucidate the mechanisms contributing to pathogenesis of this important vascular disease. In vitro expression analysis demonstrated loss of BMPR-II function for a number of the identified mutations. These data support the suggestion that haploinsufficiency represents the common molecular mechanism in PPH. Marked variability of the age at onset of disease was observed both within and between families. Taken together, these studies illustrate the considerable heterogeneity of
BMPR2 mutations that cause PPH, and they strongly suggest that additional factors, genetic and/or environmental, may be required for the development of the clinical phenotype.
Bronchial thermoplasty is a bronchoscopic procedure to reduce the mass of airway smooth muscle and attenuate bronchoconstriction. We examined the effect of bronchial thermoplasty on the control of ...moderate or severe persistent asthma.
We randomly assigned 112 subjects who had been treated with inhaled corticosteroids and long-acting beta2-adrenergic agonists (LABA) and in whom asthma control was impaired when the LABA were withdrawn to either bronchial thermoplasty or a control group. The primary outcome was the frequency of mild exacerbations, calculated during three scheduled 2-week periods of abstinence from LABA at 3, 6, and 12 months. Airflow, airway responsiveness, asthma symptoms, the number of symptom-free days, use of rescue medication, and scores on the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) were also assessed.
The mean rate of mild exacerbations, as compared with baseline, was reduced in the bronchial-thermoplasty group but was unchanged in the control group (change in frequency per subject per week, -0.16+/-0.37 vs. 0.04+/-0.29; P=0.005). At 12 months, there were significantly greater improvements in the bronchial-thermoplasty group than in the control group in the morning peak expiratory flow (39.3+/-48.7 vs. 8.5+/-44.2 liters per minute), scores on the AQLQ (1.3+/-1.0 vs. 0.6+/-1.1) and ACQ (reduction, 1.2+/-1.0 vs. 0.5+/-1.0), the percentage of symptom-free days (40.6+/-39.7 vs. 17.0+/-37.9), and symptom scores (reduction, 1.9+/-2.1 vs. 0.7+/-2.5) while fewer puffs of rescue medication were required. Values for airway responsiveness and forced expiratory volume in 1 second did not differ significantly between the two groups. Adverse events immediately after treatment were more common in the bronchial-thermoplasty group than in the control group but were similar during the period from 6 weeks to 12 months after treatment.
Bronchial thermoplasty in subjects with moderate or severe asthma results in an improvement in asthma control. (ClinicalTrials.gov number, NCT00214526 ClinicalTrials.gov.).
Objective: To compare effectiveness, complications, and cost of Amplatzer with surgical atrial septal defect (ASD) closure. Design: Prospective study. Setting: Tertiary cardiac referral centre. ...Patients: 43 consecutive patients (excluding non-UK residents) aged between 2.1 and 56.8 years (median 7) undergoing ASD closure. Main outcome measures: Procedural success, complications, regression of right ventricular dilatation (up to one year postprocedure), cost, inpatient stay, and home convalescent time. Results: Amplatzer ASD closure was successful in 24 of 27 (89%) patients. Surgical closure was successful in all 19 cases. Cardiac complications affecting management occurred in three (11%) of the Amplatzer group (two procedural failures, one device embolisation) and 4 of 19 (21%) surgical patients (one pericardial pain, one global pericardial effusion requiring drainage, and one patient with anaemia requiring haematinics in addition to an incidental pericardial effusion and one further incidental pericardial effusion) (p = NS). There were complications that did not affect management in a further 5 of 19 surgical patients. There was no significant difference in regression of right ventricular dilatation by six months postprocedure (median right ventricular end diastolic diameter decrease: Amplatzer group 17.5%, surgical group 15.1%; median cardiothoracic ratio decrease: Amplatzer 7.9%, surgical 7.5%). Both hospital stay and home convalescent times were significantly shorter after Amplatzer closure (median hospital stay: Amplatzer one day, surgery six days; median convalescent time: Amplatzer two weeks, surgery 5.5 weeks). Median cost was similar for both groups (Amplatzer £5375, surgical £5412). Conclusions: Amplatzer ASD closure has a lower chance of success with a single procedure than surgery. Overall, there were more complications in the surgical group but the majority of these were minor and did not require any change in management. Resolution of right ventricular dilatation over the study period was similar for both techniques. Time spent in hospital and away from work or school was shorter for the Amplatzer group. The cost of both techniques was similar.
Background Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. Objective We sought to assess the effectiveness ...and safety of BT in asthmatic patients 5 years after therapy. Methods BT-treated subjects from the Asthma Intervention Research 2 trial ( ClinicalTrials.gov NCT01350414 ) were evaluated annually for 5 years to assess the long-term safety of BT and the durability of its treatment effect. Outcomes assessed after BT included severe exacerbations, adverse events, health care use, spirometric data, and high-resolution computed tomographic scans. Results One hundred sixty-two (85.3%) of 190 BT-treated subjects from the Asthma Intervention Research 2 trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and emergency department (ED) visits and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months before BT treatment (average 5-year reduction in proportions: 44% for exacerbations and 78% for ED visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in years 2 through 5 compared with the first year after BT. Prebronchodilator FEV1 values remained stable between years 1 and 5 after BT, despite a 18% reduction in average daily inhaled corticosteroid dose. High-resolution computed tomographic scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. Conclusions These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ED visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking inhaled corticosteroids and long-acting β2 -agonists.
Objective:
To describe the technical aspects and outcome of duct occlusion in adults over a 12‐year period.
Methods:
A single center review of all transcatheter duct closures performed between 2000 ...and 2012.
Results:
Of 518 transcatheter duct closures performed, 31 patients were over the age of 16 at the time of procedure (6%). In 10 of the 31 cases, it was not possible to cross the duct from the pulmonary artery. In 4 of those, the duct was small enough to be closed with coils delivered from the aorta (although 1 required a second procedure for a residual shunt). In the remaining 6 cases, it was necessary to cross the duct from the aorta and create an arterio‐venous “circuit” using a snare to deliver an Amplatzer device from the femoral vein. In none of the 487 children who underwent transcatheter duct closure during the same time period was it necessary to deliver the device using an arterio‐venous wire circuit. The increased complexity of the procedure in adults compared with children was further reflected by longer procedure times (median of 37 minutes in adults vs. 24 minutes in children P < 0.01) and longer fluoroscopy times (median of 8.4 minutes in adults vs. 4.3 minutes in children P < 0.025). There were no major complications.
Conclusions:
Closure of the arterial duct in adults is safe and effective but ductal anatomy may differ from that seen in childhood, making transcatheter closure technically much more demanding than in children. (J Interven Cardiol 2012;25:501–504)
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