We must take a One Health approach to improve pandemic infection control.

The Covid-19 pandemic must serve as a wake-up call to work more collaboratively between medical and veterinary practitioners, biologists and environmentalists say Camilla Benfield, David Heymann, Judy MacArthur Clark, AJ Trees and Babulal Sethia.

Immediate and Midterm Cardiac Remodeling After Surgical Pulmonary Valve Replacement in Adults With Repaired Tetralogy of Fallot: A Prospective Cardiovascular Magnetic Resonance and Clinical Study.

BACKGROUND: Pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot provides symptomatic benefit and right ventricular (RV) volume reduction. However, data on the rate of ventricular structural and functional adaptation are scarce. We aimed to assess immediate and midterm post-PVR changes and predictors of reverse remoeling. METHODS: Fifty-seven patients with repaired tetralogy of Fallot (age ≥16 y; mean age, 35.8±10.1 y; 38 male) undergoing PVR were prospectively recruited for cardiovascular magnetic resonance performed before PVR (pPVR), immediately after PVR (median, 6 d), and midterm after PVR (mPVR; median, 3 y). RESULTS: There were immediate and midterm reductions in indexed RV end-diastolic volumes and RV end-systolic volumes (RVESVi) (indexed RV end-diastolic volume pPVR versus immediately after PVR versus mPVR, 156.1±41.9 versus 104.9±28.4 versus 104.2±34.4 mL/m2; RVESVi pPVR versus immediately after PVR versus mPVR, 74.9±26.2 versus 57.4±22.7 versus 50.5±21.7 mL/m2; P<0.01). Normal postoperative diastolic and systolic RV volumes (the primary end point) achieved in 70% of patients were predicted by a preoperative indexed RV end-diastolic volume ≤158 mL/m2 and RVESVi ≤82 mL/m2. RVESVi showed a progressive decrease from baseline to immediate to midterm follow-up, indicating ongoing intrinsic RV functional improvement after PVR. Left ventricular ejection fraction improved (pPVR versus mPVR, 59.4±7.6% versus 61.9±6.8%; P<0.01), and right atrial reverse remodeling occurred (pPVR versus mPVR, 15.2±3.4 versus 13.8±3.6 cm2/m2; P<0.01). Larger preoperative RV outflow tract scar was associated with a smaller improvement in post-PVR RV/left ventricular ejection fraction. RV ejection fraction and peak oxygen uptake predicted mortality (P=0.03) over a median of 9.5 years of follow-up. CONCLUSIONS: Significant right heart structural reverse remodeling takes place immediately after PVR, followed by a continuing process of further biological remodeling manifested by further reduction in RVESVi. PVR before RVESVi reaches 82 mL/m2 confers optimal chances of normalization of RV function.

Reframing undergraduate medical education in global health: Rationale and key principles from the Bellagio Global Health Education Initiative.

Global health education (GHE) continues to be a growing initiative in many medical schools across the world. This focus is no longer limited to participants from high-income countries and has expanded to institutions and students from low- and middle-income settings. With this shift has come a need to develop meaningful curricula through engagement between educators and learners who represent the sending institutions and the diverse settings in which GHE takes place. The Bellagio Global Health Education Initiative (BGHEI) was founded to create a space for such debate and discussion and to generate guidelines towards a universal curriculum for global health. In this article, we describe the development and process of our work and outline six overarching principles that ought to be considered when adopting an inclusive approach to GHE curriculum development.

Contemporary cardiac surgery for adults with congenital heart disease.

OBJECTIVE: Advances in early management of congenital heart disease (CHD) have led to an exponential growth in adults with CHD (ACHD). Many of these patients require cardiac surgery. This study sought to examine outcome and its predictors for ACHD cardiac surgery. METHODS: This is an observational cohort study of prospectively collected data on 1090 consecutive adult patients with CHD, undergoing 1130 cardiac operations for CHD at the Royal Brompton Hospital between 2002 and 2011. Early mortality was the primary outcome measure. Midterm to longer-term survival, cumulative incidence of reoperation, other interventions and/or new-onset arrhythmia were secondary outcome measures. Predictors of early/total mortality were identified. RESULTS: Age at surgery was 35±15 years, 53% male, 52.3% were in New York Heart Association (NYHA) class I, 37.2% in class II and 10.4% in class III/IV. Early mortality was 1.77% with independent predictors NYHA class ≥ III, tricuspid annular plane systolic excursion (TAPSE) <15 mm and female gender. Over a mean follow-up of 2.8±2.6 years, 46 patients died. Baseline predictors of total mortality were NYHA class ≥ III, TAPSE <15 mm and non-elective surgery. The number of sternotomies was not independently associated with neither early nor total mortality. At 10 years, probability of survival was 94%. NYHA class among survivors was significantly improved, compared with baseline. CONCLUSIONS: Contemporary cardiac surgery for ACHD performed at a single, tertiary reference centre with a multidisciplinary approach is associated with low mortality and improved functional status. Also, our findings emphasise the point that surgery should not be delayed because of reluctance to reoperate only.

Clinical outcomes of surgical pulmonary valve replacement after repair of tetralogy of Fallot and potential prognostic value of preoperative cardiopulmonary exercise testing.

BACKGROUND: Indications for surgical pulmonary valve replacement (PVR) after repair of tetralogy of Fallot have recently been broadened to include asymptomatic patients. METHODS AND RESULTS: The outcomes of PVR in adults after repair of tetralogy of Fallot at a single tertiary center were retrospectively studied. Preoperative cardiopulmonary exercise testing was included. Mortality was the primary outcome measure. In total, 221 PVRs were performed in 220 patients (130 male patients; median age, 32 years; range, 16-64 years). Homografts were used in 117 patients, xenografts in 103 patients, and a mechanical valve in 1 patient. Early (30-day) mortality was 2%. Overall survival was 97% at 1 year, 96% at 3 years, and 92% at 10 years. Survival after PVR in the later era (2005-2010; n=156) was significantly better compared with survival in the earlier era (1993-2004; n=65; 99% versus 94% at 1 year and 98% versus 92% at 3 years, respectively; P=0.019). Earlier era patients were more symptomatic preoperatively (P=0.036) with a lower preoperative peak oxygen consumption (peak Vo2; P<0.001). Freedom from redo surgical or transcatheter PVR was 98% at 5 years and 96% at 10 years for the whole cohort. Peak Vo2, E/CO2 slope (ratio of minute ventilation to carbon dioxide production), and heart rate reserve during cardiopulmonary exercise testing predicted risk of early mortality when analyzed with logistic regression analysis; peak Vo2 emerged as the strongest predictor on multivariable analysis (odds ratio, 0.65 per 1 mL·kg⁻¹·min⁻¹; P=0.041). CONCLUSIONS: PVR after repair of tetralogy of Fallot has a low and improving mortality, with a low need for reintervention. Preoperative cardiopulmonary exercise testing predicts surgical outcome and should therefore be included in the routine assessment of these patients.

Early postoperative outcomes following surgical repair of complete atrioventricular septal defects: is down syndrome a risk factor?

OBJECTIVE: To evaluate the impact of Down syndrome on the early postoperative outcomes of children undergoing complete atrioventricular septal defect repair. DESIGN: Retrospective cohort study. SETTING: Single tertiary pediatric cardiac center. PATIENTS: All children admitted to PICU following biventricular surgical repair of complete atrioventricular septal defect from January 2004 to December 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 107 children, 67 with Down syndrome, were included. Children with Down syndrome were operated earlier: 4 months (interquartile range, 3.5-6.6) versus 5.7 months (3-8.4) for Down syndrome and non-Down syndrome groups, respectively (p < 0.01). There was no early postoperative mortality. There was no significant difference in the prevalence of dysplastic atrioventricular valve between the two groups. Two children (2.9%) from Down syndrome and three children (7.5%) from non-Down syndrome group required early reoperation (p = 0.3). Junctional ectopic tachycardia was the most common arrhythmia, and the prevalence of junctional ectopic tachycardia was similar between the two groups (9% and 10% in Down syndrome and non-Down syndrome, respectively, p = 1). One patient from each group required insertion of permanent pacemaker for complete heart block. Children with Down syndrome had significantly higher prevalence of noncardiac complications, that is, pneumothorax, pleural effusions, and infections (p < 0.01), than children without Down syndrome. There was a trend for longer duration of mechanical ventilation in children with Down syndrome (41 hr [20-61 hr] vs 27.5 hr [15-62 hr], p = 0.2). However, there was no difference in duration of PICU stay between the two groups (2 d [1.3-3 d] vs 2 d [1-3 d], p = 0.9, respectively). CONCLUSIONS: In our study, we found no difference in the prevalence of atrioventricular valve dysplasia between children with and without Down syndrome undergoing complete atrioventricular septal defect repair. This finding contrasts with previously published data, and further confirmatory studies are required. Although clinical outcomes were similar, children with Down syndrome had a significantly higher prevalence of noncardiac complications in the early postoperative period than children without Down syndrome.

Passive stiffness of myocardium from congenital heart disease and implications for diastole.

BACKGROUND: In ventricular dilatation or hypertrophy, an elevated end-diastolic pressure is often assumed to be secondary to increased myocardial stiffness, but stiffness is rarely measured in vivo because of difficulty. We measured in vitro passive stiffness of volume- or pressure-overloaded myocardium mainly from congenital heart disease. METHODS AND RESULTS: Endocardial ventricular biopsies were obtained at open heart surgery (n=61; pressure overload, 36; volume-overload, 19; dilated cardiomyopathy, 4; normal donors, 2). In vitro passive force-extension curves and the stiffness modulus were measured in skinned tissue: muscle strips, strips with myofilaments extracted (mainly extracellular matrix), and myocytes. Collagen content (n=38) and titin isoforms (n=16) were determined. End-diastolic pressure was measured at cardiac catheterization (n=14). Pressure-overloaded tissue (strips, extracellular matrix, myocytes) had a 2.6- to 7.0-fold greater force and stiffness modulus than volume-overloaded tissue. Myocyte force and stiffness modulus at short stretches (0.05 resting length, L(0)) was pressure-overloaded >normal approximately volume-overloaded>dilated cardiomyopathy. Titin N2B:N2BA isoform ratio varied little between conditions. The extracellular matrix contributed more to force at 0.05 L(0) in pressure-overloaded (35.1%) and volume-overloaded (17.4%) strips than normal myocardium. Stiffness modulus increased with collagen content in pressure-overloaded but not volume-overloaded strips. In vitro stiffness modulus at 0.05 L(0) was a good predictor of in vivo end-diastolic pressure for pressure-overloaded but not volume-overloaded ventricles and estimated normal end-diastolic pressure as 5 to 7 mm Hg. CONCLUSIONS: An elevated end-diastolic pressure in pressure-overloaded, but not volume-overloaded, ventricles was related to increased myocardial stiffness. The greater stiffness of pressure-overloaded compared with volume-overloaded myocardium was due to the higher stiffness of both the extracellular matrix and myocytes. The transition from normal to very-low stiffness myocytes may mark irreversible dilatation.

Current options and outcomes for the management of atrioventricular septal defect.

A wealth of experience has been gained in the management of atrioventricular septal defect (AVSD) since the first complete correction of this malformation in 1955. The success of surgical therapy followed an enhanced understanding of morphology and physiology as well as major improvements in imaging of this congenital heart defect. Therapeutic success in the management of patients with AVSD has been extended to include those with associated lesions such as tetralogy of Fallot, double outlet right ventricle and relative degrees of ventricular hypoplasia. Although operative mortality is low and long-term survival is relatively good, important detrimental residual or AVSD-related complications such as left atrioventricular valve regurgitation, left ventricular outflow tract obstruction still carry significant late morbidity in a proportion of patients. This article reviews our current understanding of the morphology of this defect, aspects of diagnosis and surgical treatment options.

Total anomalous pulmonary venous connection to the supradiaphragmatic inferior vena cava.

Total anomalous pulmonary venous connection to the inferior vena cava is a rare form of total anomalous pulmonary venous connection infrequently described in the literature. We report two cases where the pulmonary venous connection was to the supradiaphragmatic portion of the inferior vena cava. In both patients, preoperative echocardiography findings were misleading, which suggested a cardiac type of total anomalous pulmonary venous connection.

A retrospective review in 50 patients with subaortic stenosis and intact ventricular septum: 5-year surgical experience.

We reviewed the surgical outcomes in adults and children with subaortic stenosis and intact ventricular septum in the current era. The case notes of 50 patients were reviewed for retrospective evaluation of preoperative, intraoperative and postoperative data. Data of primary operations during the period 2000-2005 were compared with data from patients who had re-do surgery during the same period. Thirty-five patients had primary operation and 15 patients had re-do surgery. The median age at primary operation was eight years (range 3 to 44), at second operation was 14 years (range 9 to 26) and at third operation was 15 (range 9 to 47). The entire group had been followed up postoperatively for a median of 2.5 years (range 0 to 5). Pre-operatively, aortic regurgitation was moderate in 13 and severe in three patients. Moderate to severe aortic regurgitation was present in 7 (20%) patients with primary operations and 9 (60%) patients with re-do surgery (P=0.01). Reviewing the first operations of all the re-dos (15 patients) in our series, one patient had myectomy and the rest (14 patients) had isolated resection. Aortic valve regurgitation is more prevalent in patients with recurrent subaortic stenosis. Addition of myectomy is better than shelf resection only.

Adult congenital heart disease: intensive care management and outcome prediction.

OBJECTIVE: Improved patient survival and increasingly complex surgery have expanded the requirement for specialist care for patients with adult congenital heart disease (ACHD). Despite the recent publications of management guidelines for ACHD, data concerning optimal patterns of care in the peri-operative/critical care period of this challenging population are sparse. The aims of the current study were to therefore to determine the pattern of intensive care unit (ICU) management, resource utilisation and predictors of mortality in critically ill ACHD patients. DESIGN, SETTING AND PATIENTS: Data were collected prospectively for patients with ACHD stratified for complexity of disease admitted to the ICU of a tertiary cardiothoracic centre (1997-2002). Multivariate analysis of pre-operative indices as predictors of mortality was performed. Of 342 ACHD admissions (total mortality 4.4%, simple 0%, moderate/complex 10.6%), the requirement for specialist investigations and interventions was high, reflected in ICU admission costs per patient (simple $5391+/-130, moderate $13218+/-261, complex $30074+/-689). Standard severity of illness scoring systems did not accurately predict mortality; however, abnormal pre-operative thyroid function (p=0.0048), creatinine (p=0.0032) and bilirubin (p=0.0021) were highly predictive of mortality. CONCLUSIONS: Peri-operative mortality in patients with ACHD is low overall but varies with disease complexity. Such patients have a high requirement for specialist ICU investigation/intervention. Although standard severity of illness scoring is unhelpful, simple pre-operative parameters may predict peri-operative mortality. These findings reflect the requirement for specialist care, and have implications for planning service provision, training and operative consent in ACHD patients.

Prolapse of the antero-superior leaflet of the tricuspid valve secondary to congenital anomalies of the valvar and sub-valvar apparatus: a rare cause of severe tricuspid regurgitation.

Congenital anomalies of the tricuspid valve, and/or its supporting apparatus, leading to severe tricuspid regurgitation are rare. Although well tolerated in early childhood, long-standing and progressive volume loading of the right heart leads to symptoms of decreased exercise tolerance, and may predispose to arrhythmias in the long term. We report three cases of severe tricuspid regurgitation related to anomalies of the cords supporting the antero-superior leaflet of the tricuspid valve. Shortened cords leading to tethering of the leaflet were seen in two cases, and hypoplasia of the leaflet in the other. In all cases, the regurgitant jet was directed posteriorly towards the coronary sinus and atrial septum. Surgical repair was possible in one case, while it proved necessary to replace the valve in a second. The third child is asymptomatic and under regular review.

A tunnel from the left sinus of Valsalva to the right atrium.

We describe an individualised approach in the rare situation of a tunnel between the left aortic sinus of Valsalva and the junction of the superior caval vein with the right atrium. It is necessary, in this rare anomaly, to identify the origin of the left coronary artery prior to intervention.

Congenitally corrected transposition: size of the pulmonary trunk and septal malalignment.

BACKGROUND: In hearts with congenitally corrected transposition of the great arteries, the atrial and ventricular septums are usually malaligned. This is associated with an abnormal location of the atrioventricular conduction system. However, well-aligned septums and normally positioned atrioventricular conduction tissues have been found in a few cases, some of which also happened to have a small or atretic pulmonary trunk. Our aim was to determine whether septal alignment could be predicted on the basis of the size of the pulmonary trunk. Potentially this could provide a guide to the disposition of the atrioventricular conduction tissues. METHODS: We examined 14 hearts. In all cases there was usual atrial arrangement. We carried out histologic examination of the sites of the atrioventricular conduction tissues in 1 heart. RESULTS: We found a statistically significant correlation between the size of the pulmonary trunk and the degree of septal malalignment. In the presence of a small or atretic pulmonary trunk, the septums were well aligned. Our histologic study of one such specimen revealed dual atrioventricular nodes connecting to a sling of conduction tissue. This suggests that presence of a postero-inferiorly situated atrioventricular conduction bundle in addition to an anteriorly located bundle may be anticipated when the septums are well aligned. CONCLUSIONS: The presence of a small or atretic pulmonary trunk in congenitally corrected transposition of the great arteries is associated with good septal alignment. This should alert the surgeon to the possibility of a slinglike arrangement of the atrioventricular conduction system.

Surgical aortic valvotomy in infancy: impact of leaflet morphology on long-term outcomes.

BACKGROUND: Surgical valvotomy for critical aortic stenosis in children enables relatively accurate commissurotomies to be fashioned, resulting in the formation of two or three leaflets. We hypothesized that outcomes after surgery may be best in patients in whom three leaflets are produced. METHODS: A retrospective review of infants undergoing primary surgical valvotomy at our institution during a 12-year period was carried out. Patients who had additional intracardiac defects were excluded. Clinical and echocardiographic follow-up data were analyzed. RESULTS: Fifty-four patients fulfilled the study criteria. Median age at surgery was 3 weeks (range, 0 to 51 weeks). Commissurotomy resulted in bileaflet anatomy in 41 patients (group A) and trileaflet anatomy in 13 patients (group B). Operative mortality was 5% in group A and 0% in group B (p = 1.0). In group A, 18 patients required one or more aortic valve reinterventions, including valve replacement in 8 patients. In group B, there was only one reintervention (repeat valvotomy). Kaplan-Meier analysis showed that at 10 years, comparisons of group A versus group B were as follows: actuarial survival, 85% versus 100% (p = 0.15); freedom from reintervention, 33% versus 92% (p = 0.01); freedom from aortic reoperation, 45% versus 92% (p = 0.04); and freedom from aortic valve replacement, 57% versus 100% (p = 0.07). CONCLUSIONS: Long-term outcomes after aortic valvotomy are significantly better in infants in whom surgery results in trileaflet rather than bileaflet anatomy. Preoperative evaluation of valve morphology may enable selection of a group of patients in whom results of surgery are excellent.

Midterm results after restoration of the morphologically left ventricle to the systemic circulation in patients with congenitally corrected transposition of the great arteries.

OBJECTIVE: This study was undertaken to determine the outcomes of patients with congenitally corrected transposition of the great arteries after restoration of the morphologically left ventricle to the systemic circulation. METHODS: Between November 1991 and June 2001, a total of 54 patients (median age 3.2 years, range 7 weeks-40 years) with either congenitally corrected transposition of the great arteries (n = 51) or atrioventricular discordance with double-outlet right ventricle (n = 3) underwent anatomic repair. This comprised a Senning procedure in all cases plus arterial switch (double-switch group) in 29 cases (53.7%), plus a Rastelli procedure (Rastelli-Senning group) in 22 cases (40.7%), and plus intraventricular rerouting (Senning-tunnel group) in 3 cases (5.6%). Left ventricular training by PA banding was performed before the double-switch operation in 9 of 29 cases (31%). Follow-up is complete (median 4.4 years). RESULTS: Early mortality was 5.6% (n = 3), with 2 late deaths. Kaplan-Meier survivals (+/- SEM) were 94.4% +/- 3.1% at 1 year and 89.7% +/- 4.4% at 9 years. Survivals at 7 years were 84.9% +/- 7.1% in the double-switch group and 95.5% +/- 4.4% in the Rastelli-Senning group (P =.32). Of the 49 survivors, 46 (94%) were in New York Heart Association functional class I. Six have acquired new left ventricular dilatation or impaired systolic ventricular function. Four patients in the double-switch group had moderate aortic valve regurgitation develop, and 2 of them required valve replacement. Overall freedoms from reoperation at 1 and 9 years were 94.2% +/- 3.3% and 77.5% +/- 9.0%, with no significant difference between the groups (P =.60). CONCLUSIONS: Anatomic repair of congenitally corrected transposition of the great arteries can be carried out with low early mortality. Excellent functional status can be achieved, with good midterm survival. Continued surveillance is necessary for patents with valved conduits and to determine the longer-term function of the aortic valve and the morphologically left ventricle in the systemic circulation.