Universal Artifacts Affect the Branching of Phylogenetic Trees, Not Universal Scaling Laws

The superficial resemblance of phylogenetic trees to other branching structures allows searching for macroevolutionary patterns. However, such trees are just statistical inferences of particular historical events. Recent meta-analyses report finding regularities in the branching pattern of phylogenetic trees. But is this supported by evidence, or are such regularities just methodological artifacts? If so, is there any signal in a phylogeny?In order to evaluate the impact of polytomies and imbalance on tree shape, the distribution of all binary and polytomic trees of up to 7 taxa was assessed in tree-shape space. The relationship between the proportion of outgroups and the amount of imbalance introduced with them was assessed applying four different tree-building methods to 100 combinations from a set of 10 ingroup and 9 outgroup species, and performing covariance analyses. The relevance of this analysis was explored taking 61 published phylogenies, based on nucleic acid sequences and involving various taxa, taxonomic levels, and tree-building methods.All methods of phylogenetic inference are quite sensitive to the artifacts introduced by outgroups. However, published phylogenies appear to be subject to a rather effective, albeit rather intuitive control against such artifacts. The data and methods used to build phylogenetic trees are varied, so any meta-analysis is subject to pitfalls due to their uneven intrinsic merits, which translate into artifacts in tree shape. The binary branching pattern is an imposition of methods, and seldom reflects true relationships in intraspecific analyses, yielding artifactual polytomies in short trees. Above the species level, the departure of real trees from simplistic random models is caused at least by two natural factors--uneven speciation and extinction rates; and artifacts such as choice of taxa included in the analysis, and imbalance introduced by outgroups and basal paraphyletic taxa. This artifactual imbalance accounts for tree shape convergence of large trees.There is no evidence for any universal scaling in the tree of life. Instead, there is a need for improved methods of tree analysis that can be used to discriminate the noise due to outgroups from the phylogenetic signal within the taxon of interest, and to evaluate realistic models of evolution, correcting the retrospective perspective and explicitly recognizing extinction as a driving force. Artifacts are pervasive, and can only be overcome through understanding the structure and biological meaning of phylogenetic trees. Catalan Abstract in Translation S1

Prognostic Effects of Pulmonary Valve Replacement in Repaired Tetralogy of Fallot: Results From a Large Multicenter Study

Introduction: The prognostic impact and optimal timing of pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF) remains a subject of debate. The objective of this study was to determine whether PVR was associated with beneficial outcome. Methods: In this multicenter, case-controlled study, clinical, ECG, cardiac magnetic resonance (CMR) and outcome data of rTOF patients were collected. A propensity score for PVR was created to adjust for baseline differences between PVR and non-PVR patients. A frailty failure time model was used to determine the association of PVR, with matching on propensity score and adjustment for other risk factors, on time to the composite of death/sustained ventricular tachycardia (VT). In addition, differential association between impact of PVR and outcome according to predefined ‘proactive’ and ‘conservative’ (see figure) criteria was studied. Results: A total of 440 PVR patients (age 24±13 years at baseline CMR, 58% male, RV ejection fraction (EF) 47±8%, QRS duration 148±27ms) and 537 non-PVR patients (age 29±15 years, 53% male, RV EF 51±8%, QRS duration 140±27ms) were included. During follow-up of 5.3±3.1 years, 41 events occurred (30 death, 11 sustained VT). The adjusted hazard ratio (HR) for death/sustained VT for patients with versus without PVR was 0.65 (95% CI: 0.31, 1.36, p=0.25). There was an increasing hazard of event across prespecified ordered PVR x criteria subgroups (Figure; P=0.044 for proactive, P=0.002 for conservative). There was a two-fold risk (hazard ratio=2.15, 95% CI: 1.34, 3.46) comparing each adjacent subgroup, suggesting benefit of PVR when conservative criteria were met, and lack of benefit of PVR when criteria were not met. A roughly similar pattern was seen according to proactive criteria. Conclusions: In this multicenter, 5-year follow-up study in patients with rTOF, conservative guidelines seemed useful in selecting patients for PVR. Longer follow-up is necessary to confirm these findings

A propensity score-adjusted analysis of clinical outcomes after pulmonary valve replacement in tetralogy of Fallot

OBJECTIVE: To determine the association of pulmonary valve replacement (PVR) with death and sustained ventricular tachycardia (VT) in patients with repaired tetralogy of Fallot (rTOF). METHODS: Subjects with rTOF and cardiac magnetic resonance from an international registry were included. A PVR propensity score was created to adjust for baseline differences. PVR consensus criteria were predefined as pulmonary regurgitation >25% and ≥2 of the following criteria: right ventricular (RV) end-diastolic volume >160 mL/m2, RV end-systolic volume >80 mL/m2, RV ejection fraction (EF) 160 ms. The primary outcome included (aborted) death and sustained VT. The secondary outcome included heart failure, non-sustained VT and sustained supraventricular tachycardia. RESULTS: In 977 rTOF subjects (age 26±15 years, 45% PVR, follow-up 5.3±3.1 years), the primary and secondary outcomes occurred in 41 and 88 subjects, respectively. The HR for subjects with versus without PVR (time-varying covariate) was 0.65 (95% CI 0.31 to 1.36; P=0.25) for the primary outcome and 1.43 (95% CI 0.83 to 2.46; P=0.19) for the secondary outcome after adjusting for propensity and other factors. In subjects (n=426) not meeting consensus criteria, the HR for subjects with (n=132) versus without (n=294) PVR was 2.53 (95% CI 0.79 to 8.06; P=0.12) for the primary outcome and 2.31 (95% CI 1.07 to 4.97; P=0.03) for the secondary outcome. CONCLUSION: In this large multicentre rTOF cohort, PVR was not associated with a reduced rate of death and sustained VT at an average follow-up of 5.3 years. Additionally, there were more events after PVR compared with no PVR in subjects not meeting consensus criteria

Multimodality imaging: Bird’s eye view from The European Society of Cardiology Congress 2016

Cardiolog