HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis.

Although most cervical human papillomavirus type 16 (HPV16) infections become undetectable within 1-2 years, persistent HPV16 causes half of all cervical cancers. We used a novel HPV whole-genome sequencing technique to evaluate an exceptionally large collection of 5,570 HPV16-infected case-control samples to determine whether viral genetic variation influences risk of cervical precancer and cancer. We observed thousands of unique HPV16 genomes; very few women shared the identical HPV16 sequence, which should stimulate a careful re-evaluation of the clinical implications of HPV mutation rates, transmission, clearance, and persistence. In case-control analyses, HPV16 in the controls had significantly more amino acid changing variants throughout the genome. Strikingly, E7 was devoid of variants in precancers/cancers compared to higher levels in the controls; we confirmed this in cancers from around the world. Strict conservation of the 98 amino acids of E7, which disrupts Rb function, is critical for HPV16 carcinogenesis, presenting a highly specific target for etiologic and therapeutic research.

Echocardiographic Strain to Predict Need for Transplant or Mortality in Fontan Patients with Hypoplastic Left Heart Syndrome.

Despite recent advances, hypoplastic left heart syndrome (HLHS) patients subsequent to the Fontan still have significant morbidity and mortality. Some require heart transplant due to systemic ventricular dysfunction. Limited data exist on timing for transplant referral. This study aims to correlate systemic ventricular strain by echocardiography to transplant-free survival. HLHS patients who had Fontan palliation at our institution were included. Patients were divided into: 1) Required transplant or experienced mortality (composite end point); 2) Did not require transplant or survived. For those who experienced the composite endpoint, the last echocardiogram prior to the composite outcome was used, while for those who did not experience the composite endpoint the last echocardiogram obtained was used. Several qualitative and quantitative parameters were analyzed with focus on strain parameters. Ninety-five patients with HLHS Fontan palliation were identified. Sixty-six had adequate images and eight (12%) experienced transplant or mortality. These patients had greater myocardial performance index by flow Doppler (0.72 versus 0.53, p = 0.01), higher systolic/diastolic duration ratio (1.51 versus 1.13, p = 0.02), lower fractional area change (17.65 versus 33.99, p < 0.01), lower global longitudinal strain (GLS) (-8.63 versus - 17.99, p < 0.01), lower global longitudinal strain rate (GLSR) (- 0.51 versus - 0.93, p < 0.01), lower global circumferential strain (GCS) (-6.68 versus -18.25, p < 0.01), and lower (GCSR) global circumferential strain rate (-0.45 versus -1.01, p < 0.01). ROC analysis demonstrated predictive value for GLS - 7.6 (71% sensitive, 97% specific, AUC 81%), GLSR -0.58 (71% sensitive, 88% specific, AUC 82%), GCS - 10.0 (86% sensitive, 91% specific, AUC 82%), and GCSR -0.85 (100% sensitive, 71% specific, AUC 90%). GLS and GCS can help predict transplant-free survival in patients with hypoplastic left heart syndrome having undergone Fontan palliation. Higher strain values (closer to zero) may be a helpful tool in determining when transplant evaluation is warranted in these patients.

Adverse events in facial plastic surgery: Data-driven insights into systems, standards, and self-assessment.

PURPOSE: Complications in facial plastic surgery can lead to pain, suffering, and permanent harm. Yet, the etiology and outcomes of adverse events are understudied. This study aims to determine the etiology and outcomes of adverse events reported in aesthetic facial plastic surgery and identify quality improvement opportunities. MATERIAL AND METHODS: A cross-sectional survey analysis was conducted using an anonymous 22-item questionnaire distributed to members of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS). Participants were queried on demographics, practice type, and adverse events related to aesthetic facial surgeries. RESULTS: Two hundred fifty-three individuals participated; nearly half of respondents (49.0%) held membership in both AAO-HNS and AAFPRS. Of these, 40.8% of respondents reported at least one adverse event within the past 12 months of practice. A total of 194 adverse events were reported, most commonly related to facelift (n = 59/194, 30.4%), rhinoplasty (n = 55/194, 28.4%), and injection procedures (n = 38/194, 19.6%), with hematoma or seroma being the most commonly described. Most adverse events were self-limited, but approximately 68% resulted in further procedures. Surgeon error or poor judgement (n = 42) and patient non-adherence (n = 18) were the most commonly ascribed reasons for adverse events; 37.1% of participants reported a change in clinical practice after the incident. CONCLUSIONS: Adverse events were not infrequent in facial plastic surgery. Understanding these adverse events can provide impetus for tracking outcomes, standardization, and engagement with lifelong learning, self-assessment, and evaluation of practice performance.

Comparison of semi-automated versus manual quantitative right ventricular assessment in tetralogy of Fallot.

BACKGROUND: Tetralogy of Fallot is a congenital heart defect diagnosed in infancy. Assessment of right ventricular size and function is important for evaluation of patients with tetralogy of Fallot, but these quantitative measures are challenging by echocardiography. This study evaluates a semi-automated software (EchoInsight®, Epsilon Imaging) by comparing its measures to manual measures in children with tetralogy of Fallot. METHODS: Echocardiographic measurements were performed using manual techniques and semi-automated software. Right ventricular measurements included end-diastolic and end-systolic area, fractional area change, chamber dimensions, and tricuspid annular plane systolic excursion. Reliability, correlation, and agreement between manual and semi-automated measures were assessed. RESULTS: Echocardiograms for 46 patients were analysed. Intra- and inter-observer reliabilities for semi-automated measures were good with intraclass correlation coefficients all over 0.95 and 0.85, respectively. There was high correlation between manual and semi-automated methods for areas and dimensions (r = 0.91-0.98). Tricuspid annular plane systolic excursion measures and fractional area change also correlated, albeit less strongly. The semi-automated measurements of end-systolic and end-diastolic area were a 20 and 47% higher than manual methods, respectively.The semi-automated method yielded a relative 52% lower fractional area change compared to the manual method. CONCLUSIONS: The semi-automated software generates quantitative right ventricular measures in children with tetralogy of Fallot with good reliability and good correlation with manual methods for all measures, but with significant difference between manual and semi-automated techniques for area and functional measures. The specific right ventricular geometry in tetralogy of Fallot children may be why, compared to normal anatomy, greater differences were observed between the two techniques.

Improving tracheostomy care in the United Kingdom: results of a guided quality improvement programme in 20 diverse hospitals.

BACKGROUND: Inconsistent and poorly coordinated systems of tracheostomy care commonly result in frustrations, delays, and harm. Quality improvement strategies described by exemplar hospitals of the Global Tracheostomy Collaborative have potential to mitigate such problems. This 3 yr guided implementation programme investigated interventions designed to improve the quality and safety of tracheostomy care. METHODS: The programme management team guided the implementation of 18 interventions over three phases (baseline/implementation/evaluation). Mixed-methods interviews, focus groups, and Hospital Anxiety and Depression Scale questionnaires defined outcome measures, with patient-level databases tracking and benchmarking process metrics. Appreciative inquiry, interviews, and Normalisation Measure Development questionnaires explored change barriers and enablers. RESULTS: All sites implemented at least 16/18 interventions, with the magnitude of some improvements linked to staff engagement (1536 questionnaires from 1019 staff), and 2405 admissions (1868 ICU/high-dependency unit; 7.3% children) were prospectively captured. Median stay was 50 hospital days, 23 ICU days, and 28 tracheostomy days. Incident severity score reduced significantly (n=606; P<0.01). There were significant reductions in ICU (-;0.25 days month-1), ventilator (-;0.11 days month-1), tracheostomy (-;0.35 days month-1), and hospital (-;0.78 days month-1) days (all P<0.01). Time to first vocalisation and first oral intake both decreased by 7 days (n=733; P<0.01). Anxiety decreased by 44% (from 35.9% to 20.0%), and depression decreased by 55% (from 38.7% to 18.3%) (n=385; both P<0.01). Independent economic analysis demonstrated £33 251 savings per patient, with projected annual UK National Health Service savings of £275 million. CONCLUSIONS: This guided improvement programme for tracheostomy patients significantly improved the quality and safety of care, contributing rich qualitative improvement data. Patient-centred outcomes were improved along with significant efficiency and cost savings across diverse UK hospitals. CLINICAL TRIAL REGISTRATION: IRAS-ID-206955; REC-Ref-16/LO/1196; NIHR Portfolio CPMS ID 31544.

Global Tracheostomy Collaborative: data-driven improvements in patient safety through multidisciplinary teamwork, standardisation, education, and patient partnership.

There is growing recognition of the need for a coordinated, systematic approach to caring for patients with a tracheostomy. Tracheostomy-related adverse events remain a pervasive global problem, accounting for half of all airway-related deaths and hypoxic brain damage in critical care units. The Global Tracheostomy Collaborative (GTC) was formed in 2012 to improve patient safety and quality of care, emphasising knowledge, skills, teamwork, and patient-centred approaches. Inspired by quality improvement leads in Australia, the UK, and the USA, the GTC implements and disseminates best practices across hospitals and healthcare trusts. Its database collects patient-level information on quality, safety, and organisational efficiencies. The GTC provides an organising structure for quality improvement efforts, promoting safety of paediatric and adult patients. Successful implementation requires instituting key drivers for change that include effective training for health professionals; multidisciplinary team collaboration; engagement and involvement of patients, their families, and carers; and data collection that allows tracking of outcomes. We report the history of the collaborative, its database infrastructure and analytics, and patient outcomes from more than 6500 patients globally. We characterise this patient population for the first time at such scale, reporting predictors of adverse events, mortality, and length of stay indexed to patient characteristics, co-morbidities, risk factors, and context. In one example, the database allowed identification of a previously unrecognised association between bleeding and mortality, reflecting ability to uncover latent risks and promote safety. The GTC provides the foundation for future risk-adjusted benchmarking and a learning community that drives ongoing quality improvement efforts worldwide.

Added Value of Live 3-Dimensional Transesophageal Echocardiography During Procedures in Fontan Patients.

3D transesophageal echocardiography (3D-TEE) has proven useful and accurate during some operating room (OR), interventional cardiac catheterization (Cath), and electrophysiologic (EP) procedures. The use of 3D-TEE during similar procedures in patients who have undergone Fontan surgery and its additional value have not been previously reported. To determine if live 3D-TEE during procedures post Fontan has added value, 3D-TEEs in 58 post-Fontan patients over a 5-year study period were reviewed. Additional information provided by 3D-TEE (over 2D-TEE) was classified into the following: A: new information which changed/refined the plan and 0: no new important information. Pre- and post-bypass OR 3D-TEEs were counted as one study. A total of 67 3D-TEEs (41 Cath, 13 OR, and 13 EP procedures) were performed. Median age was 14 years (6-39 years). Median weight was 47 kg (21-109 kg). In Cath procedures, only 2/41 (5%) were graded A (R to L atrial level shunt [Fontan leak], n = 1; thrombus in pulmonary artery stump, n = 1). In the OR, 6/13 (46%) were graded A (atrioventricular valvuloplasty, n = 1; neo-aortic valvuloplasty, n = 1; relief of systemic and pulmonary venous outflow obstruction, n = 2 and n = 2; respectively). In EP procedures, 4/13 (31%) were graded A (thrombus, n = 3; mapping for lead placement to assist in multisite pacing for dyssynchrony, n = 1). 3D-TEE of Fontan improved visualization and frequently added value in the OR/EP lab and may be helpful in select catheterization cases. Future studies with a larger sample could build on this data to identify when 3D-TEE will be most useful.

Comparison of Semi-Automated Versus Manual Quantitative Right Ventricular Assessment in Hypoplastic Left Heart Syndrome.

Quantitative echocardiographic evaluation is important for systemic right ventricles, but its asymmetric shape makes this challenging and time consuming when performed manually. Semi-automated software could make these quantitative measures easier to accomplish in the clinical setting. We hypothesized that semi-automated software would approximate manual measures of right ventricular size and function. Children with hypoplastic left heart who had echocardiograms were prospectively identified. These measurements were performed using manual and semi-automated techniques: end-diastolic and end-systolic area, fractional area change (FAC), dimensions (longitudinal, basal and mid-cavitary diameters), and tricuspid annular plane systolic excursion (TAPSE). Agreement between measures was evaluated. Sixty-three echocardiograms were analyzed. Intra- and inter-observer reliability was acceptable and similar between methods except that inter-observer reliability for the manual method was superior for TAPSE. Correlation between methods was high (r > 0.9, p < 0.001) for most of the measures. Correlation for FAC was r = 0.79, and for TAPSE the correlation was r = 0.61 (both p < 0.001). The percent relative difference between manual and semi-automated methods was less than 6% for most measures. End-systolic area and FAC had a relative difference of 10% and 11% respectively. The only measure with substantial bias between the manual and semi-automated methods was TAPSE which had a relative difference of 52%. EchoInsight® semi-automated software provides similar measures of right ventricular dimensions and FAC in patients with hypoplastic left heart compared to manual measures. Measures of TAPSE do not correlate well between manual and semi-automated methods. Further research is warranted on the use of semi-automated analyses in this patient population.

Evaluation of TypeSeq, a Novel High-Throughput, Low-Cost, Next-Generation Sequencing-Based Assay for Detection of 51 Human Papillomavirus Genotypes.

BACKGROUND: Human papillomaviruses (HPV) cause over 500 000 cervical cancers each year, most of which occur in low-resource settings. Human papillomavirus genotyping is important to study natural history and vaccine efficacy. We evaluated TypeSeq, a novel, next-generation, sequencing-based assay that detects 51 HPV genotypes, in 2 large international epidemiologic studies. METHODS: TypeSeq was evaluated in 2804 cervical specimens from the Study to Understand Cervical Cancer Endpoints and Early Determinants (SUCCEED) and in 2357 specimens from the Costa Rica Vaccine Trial (CVT). Positive agreement and risks of precancer for individual genotypes were calculated for TypeSeq in comparison to Linear Array (SUCCEED). In CVT, positive agreement and vaccine efficacy were calculated for TypeSeq and SPF10-LiPA. RESULTS: We observed high overall and positive agreement for most genotypes between TypeSeq and Linear Array in SUCCEED and SPF10-LiPA in CVT. There was no significant difference in risk of precancer between TypeSeq and Linear Array in SUCCEED or in estimates of vaccine efficacy between TypeSeq and SPF10-LiPA in CVT. CONCLUSIONS: The agreement of TypeSeq with Linear Array and SPF10-LiPA, 2 well established standards for HPV genotyping, demonstrates its high accuracy. TypeSeq provides high-throughput, affordable HPV genotyping for world-wide studies of cervical precancer risk and of HPV vaccine efficacy.

Viral coinfection analysis using a MinHash toolkit.

BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted infection associated with cervical cancer that frequently occurs as a coinfection of types and subtypes. Highly similar sublineages that show over 100-fold differences in cancer risk are not distinguishable in coinfections with current typing methods. RESULTS: We describe an efficient set of computational tools, rkmh, for analyzing complex mixed infections of related viruses based on sequence data. rkmh makes extensive use of MinHash similarity measures, and includes utilities for removing host DNA and classifying reads by type, lineage, and sublineage. We show that rkmh is capable of assigning reads to their HPV type as well as HPV16 lineage and sublineages. CONCLUSIONS: Accurate read classification enables estimates of percent composition when there are multiple infecting lineages or sublineages. While we demonstrate rkmh for HPV with multiple sequencing technologies, it is also applicable to other mixtures of related sequences.

Development of the TypeSeq Assay for Detection of 51 Human Papillomavirus Genotypes by Next-Generation Sequencing.

We have developed a new human papillomavirus (HPV) genotyping assay for detection of 51 HPV genotypes by next-generation sequencing (NGS). The TypeSeq assay consists of 3 PCR steps that equalize viral load and each type's amplicon copies prior to genotyping by NGS, thereby maximizing multiple-type sensitivity with minimal sequencing reads. The analytical sensitivity of the TypeSeq assay is 10 copies per reaction for 49 of the 51 types, including 13 high-risk (HR) types. We tested 863 clinical cervical specimens previously evaluated with the Roche Linear Array HPV genotyping test (LA). TypeSeq achieved 94.4% positive agreement with LA for detection of any HR type. Positive agreement was 91.4% and 85.5% for HPV16 and HPV18, respectively. Low-risk (LR) types ranged from 40.0% positive agreement (HPV83) to 90.9% (HPV69). Our unique approach to HPV amplification achieved a multiple-type sensitivity comparable to that of LA, with 83.9% and 84.2% of specimens positive for multiple HPV types by TypeSeq or LA, respectively. A total of 48.2% of specimens showed perfect agreement for all 37 types common to both assays. The simplicity of our open-source TypeSeq assay allows for high-throughput yet scalable processing, with a single technician able to process up to 768 specimens within 3 days. By leveraging NGS sample multiplexing capabilities, the per-sample labor requirements are greatly reduced compared to those of traditional genotyping methods. These features and the broad spectrum of detectable types make TypeSeq highly suitable for a wide range of applications.

Predictors of a drainable suppurative adenitis among children presenting with cervical adenopathy.

OBJECTIVES: We sought to identify predictors for a drainable suppurative adenitis [DSA] among patients presenting with acute cervical lymphadenitis. METHODS: A retrospective cross sectional study of all patients admitted to an urban pediatric tertiary care emergency department over a 15 year period. Otherwise healthy patients who underwent imaging for an evaluation of cervical lymphadenitis were included. Cases were identified using a text-search module followed by manual review. We excluded immunocompromised patients and those with lymphadenopathy felt to be not directly infected (i.e. reactive) or that was not acute (symptom duration >28 days). Data collected included: age, gender, duration of symptoms, highest recorded temperature, physical exam findings, laboratory and imaging results, and surgical findings. A DSA was defined as >1.5 cm in diameter on imaging. We performed binary logistic regression to determine independent clinical predictors of a DSA. RESULTS: Three hundred sixty-one patients met inclusion criteria. Three hundred six patients (85%) had a CT scan, 55 (15%) had an ultrasound and 33 (9%) had both. DSA was identified in 71 (20%) patients. Clinical features independently associated with a DSA included absence of clinical pharyngitis, WBC >15,000/mm3, age ≤3 years, anterior cervical chain location, largest palpable diameter on exam >3 cm and prior antibiotic treatment of >24 h. The presence of fever, skin erythema, or fluctuance on examination, was not found to be predictive of DSA. CONCLUSIONS: We identified independent predictors of DSA among children presenting with cervical adenitis. Risk can be stratified into risk groups based on these clinical features.

Right Ventricular Mechanical Dyssynchrony in Hypoplastic Left Heart Syndrome: Correlation with Systolic Function and QRS Duration.

The single right ventricle (RV) in hypoplastic left heart syndrome (HLHS) often develops systolic dysfunction with time and this affects prognosis. Mechanical dyssynchrony has been reported in HLHS but has not consistently correlated with systolic function or electrical dyssynchrony. The aims of this study were to assess the relationship between RV mechanical dyssynchrony, RV systolic function, and QRS duration on surface electrocardiography. We hypothesized that surface QRS duration would not be an adequate indicator of mechanical dyssynchrony compared with dyssynchrony parameters. Retrospective analysis of echocardiograms of patients with HLHS divided into preserved vs reduced RV function. We measured two RV function parameters: (1) fractional area change (FAC) and (2) global longitudinal strain (RVGLS). We measured two dyssynchrony parameters: (1) the standard deviation of the time to peak strain for 9 segments (tPS-9) and (2) time difference between the earliest and latest time to peak strain (RV dyssynchrony index or RVDI) both corrected for R-R interval. We also measured the QRS duration from surface EKG. Mechanical dyssynchrony parameters were compared to both RV systolic function and to QRS duration. 41 patients with HLHS were identified: 21 had preserved function and 20 had reduced function defined by a FAC < 35%. The reduced function group had a significantly lower mean FAC and RVGLS. RVDI was higher in the dysfunction group and had a modest correlation with FAC (r = 0.48) and RVGLS (r = 0.57). tPS-9 was longer in the dysfunction group and had a modest correlation with FAC (r = 0.45) and RVGLS (r = 0.57). QRS duration was longer in the dysfunction group and had a modest correlation with FAC (r = 0.56) and RVGLS (r = 0.56). The weakest correlations were between QRS duration and tPS-9 (r = 0.32) and QRS duration and RVDI (r = 0.10). RV dysfunction measured by FAC was associated with mechanical dyssynchrony measured by increased RVDI and tPS-9. QRS duration was longer in the group with dysfunction but did not correlate with directly measured mechanical dyssynchrony. This may have potential implications for cardiac resynchronization therapy in univentricular patients as assessed by mechanical dyssynchrony parameters rather than QRS duration alone.

Saline Contrast Transesophageal Echocardiography in Fontan Patients: Assessment of the Presence, Type, and Size of Right to Left Shunts.

Right to left (R-L) shunts resulting in cyanosis or systemic embolization occur after the Fontan procedure. The primary modality of diagnosing these is angiography. Successful delineation of these shunts in Fontan patients using selective saline contrast transesophageal echocardiography (SCTEE) may allow for reduced radiation and contrast exposure. We hypothesized that SCTEE could accurately determine the presence, type, and semiquantitative shunt size of R-L shunts in Fontan patients. SCTEE was performed in Fontan patients undergoing angiography for clinical indications. Injections were performed in six sites: mid-Fontan, right and left pulmonary arteries, superior and inferior vena cavae, and innominate vein. R-L shunt size was subjectively graded as 0 = absent, 1 = small, and 2 = medium or large based on echo contrast density in the left atrium. SCTEE was compared to angiography. 33 patients with Fontan were studied with median age 15 years, median weight 50.1 kg, and median O2 saturation of 90% in the R-L shunt group and 95% in the no R-L shunt group. R-L shunt types included intracardiac shunts (ICS), veno-venous collaterals (VVCs), arteriovenous malformations (AVMs), and their combinations. SCTEE versus angiography results were the same for the presence, type, and size of R-L shunts in 79% (26/33). SCTEE identified shunts in 88% (29/33). Angiography identified shunts in 85% (28/33). Neither method missed any medium or large R-L shunts. SCTEE and angiography had similar accuracy. SCTEE accurately detected the presence, type, and size of R-L shunts in most Fontan patients in this study. This can be used to guide targeted angiography, reducing radiation exposure and contrast load.

Semi-automated speckle-tracking for quantitative right ventricular assessment in children and adolescents.

BACKGROUND: Assessment of right ventricular size and function is an important part of the clinical cardiac evaluation; however, these quantitative measures are challenging by echocardiography. Automated software could be useful in place of manual measurements and qualitative assessment. This study evaluates a semi-automated software by comparing automated to manual measures in normal children. METHODS: Neonates to adolescents with normal echocardiograms were prospectively enrolled. Measurements were performed using manual techniques and semi-automated software (EchoInsight®, Epsilon Imaging, Ann Arbor, Michigan, United States of America). Right ventricular measurements included end-diastolic and end-systolic area, fractional area change, chamber dimensions, and tricuspid annular plane systolic excursion. Agreement between manual and semi-automated measures was compared. RESULTS: Echocardiograms for 233 patients were included in the analysis. Intra- and inter-observer reliabilities for semi-automated measures were good with intraclass correlation coefficients all over 0.9 and 0.85, respectively. There was very strong correlation between manual and semi-automated methods for areas and dimensions (r = 0.93-0.99) and low bias (1.4-10.8%). For functional measures, tricuspid annular plane systolic excursion measures correlated well (r = 0.84), but fractional area change did not (r = 0.50). Both demonstrated significant bias (33.5-43.0%). The semi-automated method consistently underestimated fractional area change with a mean of 26.6% versus a manual mean of 36.1%. CONCLUSIONS: The semi-automated software is capable of generating quantitative right ventricular measures in children with good reliability. The software demonstrates very good correlation and low bias when compared to manual methods for right ventricular areas and dimensions. There is a significant difference between manual and semi-automated techniques for the functional measures.

Aortic Valvuloplasty or Rootplasty for Aortic Regurgitation.

At present, aortic valvuloplasty is considered an effective procedure for treatment of aortic regurgitation in pediatric patients. It has encouraging mid- and long-term results. The improved outcome is primarily related to better understanding of the functional anatomy of the normal valve and the different factors that alter it. It is also related to the realization that outcome after valvuloplasty is dependent on comprehensive repair of all of the involved components of the aortic root. Refinement in preoperative diagnosis has helped identify these abnormal components and focus the surgical approach on the needed reconstruction. Although the technical aspects of valvuloplasty are well defined, suboptimal long-term results still occur in some cases because the patch material used for valve repair can become fibrotic or calcified. This review summarizes the surgical approach to and the management of the different abnormal root components in pediatric patients with significant aortic valve regurgitation.

Myocardial Fistulisation and Coronary Arterial Ectasia in Children with Univentricular Circulation: An Under-Recognised Problem.

Among 241 children with univentricular circulation who underwent total cavopulmonary connection (Glenn or Fontan) over a 17 years period (January 2000-April 2017), we found two patients who had diffuse coronary fistulisation of their myocardium (0.8%). We also report an additional third case from Oak Lawn, Illinois, USA. One of the children had documented normal coronary arteries and myocardium at catheterisation prior to development of the fistulisation process. The same child also developed extensive veno-venous collaterals. All children had evidence of elevated pulmonary arterial pressures and were treated with a combination of pulmonary vasodilators. The presence of chronic hypoxaemia and elevated filling pressures could potentially have contributed to coronary endothelial dysfunction, thereby giving rise to the coronary vasculopathy and myocardial fistulisation. Alternatively, this myocardial fistulisation process may be present from early in life and not recognised. This may necessitate early referral for orthotopic cardiac transplantation. Diffuse fistulisation of the myocardium in children and young adults with univentricular circulation may be an under-recognised occurrence and coronary angiography should be considered in these patients.

Right Ventricular Systolic Function Parameters in Hypoplastic Left Heart Syndrome.

Assessment of the systolic function of the right ventricle (RV) in patients with hypoplastic left heart syndrome (HLHS) is important. The asymmetric shape and heavy trabeculations make accurate assessment of RV systolic function challenging. Novel measures of RV function could be helpful in distinguishing reduced versus preserved function in HLHS and may also be worse in HLHS with preserved function compared to normal controls. These novel methods offer promise, but research and clinical applicability is hindered as no cut-off values for normal function have been established. We performed a retrospective comparison of functional assessments from echocardiograms of HLHS patients with preserved and reduced RV function along with a control group of normal patients. Measures of function included fractional area change (FAC), tissue motion annular displacement of the tricuspid (TMAD-TV) and pulmonary valves (TMAD-PV), myocardial performance index (MPI), tricuspid tissue Doppler S' velocity, and RV global longitudinal strain (RVGLS). Comparisons were made between three groups: normal patients, HLHS with preserved function, and HLHS with reduced function defined as FAC < 35%. FAC was chosen as the reference as it is a historical standard. 41 HLHS patients were studied. Of these patients, 20 had HLHS with reduced function, and 21 had preserved function. They were compared with 27 age-matched, normal, controls. Comparison between HLHS and normal controls: in HLHS with preserved RV systolic function, compared to normal controls, tissue Doppler S', MPI, and TMAD-TV were all abnormal (all p < 0.05). RVGLS was not statistically different (20.5 ± 3.6% for normal vs. 17.9 ± 2.6% for HLHS with preserved function). TMAD-PV was similar between groups (16.1 ± 4.6% vs. 16.7 ± 5.1%). All measures were significantly worse (all p < 0.05) in the HLHS with reduced function group compared to normal controls. Comparison between HLHS preserved vs reduced function: in HLHS with reduced function defined by FAC < 35%, all measures were significantly worse compared to HLHS with preserved function (all p < 0.05). The cut-off values that correspond to a FAC of > 35% were 14.5% for TMAD-TV and 16% for RVGLS. All measures except RVGLS and TMAD-PV estimated worse function than controls even for HLHS with preserved function. Each of the functional measures was able to identify preserved vs reduced function in HLHS with FAC as the reference standard. Cut-off values between preserved and reduced function in HLHS were estimated for TMAD-TV and RVGLS based on a relatively small cohort. These cut-off values will aid in the research design of future studies.

Right Ventricular Longitudinal Shortening Before and After Stage I Surgical Palliation Correlates with Outcomes.

Quantification of right ventricular function is difficult, but important, in patients with single ventricles. Tissue motion annular displacement (TMAD) is an echocardiographic tool that measures displacement of the tricuspid valve relative to the apex. We evaluated TMAD, lateral annular displacement (LAD), and fractional area change (FAC) for correlation with outcomes. We measured TMAD, LAD, FAC, and other variables that may affect prognosis in patients with single right ventricle physiology pre- and post-Stage I palliation and correlated them with outcomes up to the Glenn procedure. Intra- and inter-observer variability for TMAD measurements were 2.7% (1.2-3.5%) and 6.1% (3.3-8.1%), respectively. Sixty-six subjects met the inclusion criteria. Pre-Stage I TMAD was 13.7% (SD 3.9%). TMAD had a linear relationship with FAC (r2 = 0.76). There was a correlation between TMAD and hospital stay (p = 0.044) and ECMO/arrest (p = 0.024). LAD correlated with ECMO/arrest (p = 0.045) and mortality/transplant (p = 0.049). FAC correlated with in-hospital mortality (p = 0.028). Post-Stage I TMAD was 11.8% (SD 3.7%). TMAD, LAD, and FAC all correlated with in-hospital mortality and mortality/transplant. In multivariate models, TMAD was independently predictive of weight for age Z score pre-Glenn. TMAD, FAC, and LAD correlate with clinically significant outcomes after the first-stage palliation. TMAD correlated with more outcomes than FAC and was the only measure that was independently predictive of any outcome. TMAD is a reproducible measure of RV function in this population. TMAD has prognostic value before and after first-stage palliation and may outperform more traditional measures.