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This study aimed to assess clinical, functional, and hemodynamic characteristics of heart-transplanted (HTX) patients during exercise. We performed comprehensive echocardiographic graft function assessment during invasive hemodynamic semi-supine exercise test in 57 HTX patients. According to hemodynamics findings, patients were divided into Group A: normal left ventricular (LV) filling pressure (FP): pulmonary capillary wedge pressure (PCWP) <15 mmHg at rest and <25 mmHg at peak exercise, and Group B: elevated LV-FP: PCWP ≥15 mmHg at rest or ≥25 mmHg at peak exercise. Thirty-one patients (54%) had normal LV-FP and 26 patients (46%) had elevated LV-FP. The latter had higher cumulative rejection burden (P < 0.01) and were more symptomatic (NYHA class >1) (P < 0.05), and cardiac allograft vasculopathy (CAV) was more prevalent (P < 0.05). With exercise, the changes in both left- and right-sided filling pressures were significantly increased, whereas LV longitudinal myocardial deformation was lower (P < 0.05) in patients with elevated LV-FP than in patients with normal LV-FP. No between-group difference was observed for cardiac index or LV ejection fraction (LVEF) during exercise. In conclusion, elevated LV-FP can be demonstrated in approximately 50% of HTX patients. Patients with elevated LV-FP have impaired myocardial deformation capacity, higher prevalence of CAV, and higher rejection burden, and were more symptomatic. Exercise test with the assessment of longitudinal myocardial deformation should be considered in routine surveillance of HTX patients as a marker of restrictive filling (ClinicalTrials.gov Identifier: NCT02077764)., (© 2015 Steunstichting ESOT.)

Montane barriers influence the evolutionary history of lineages by promoting isolation of populations. The effects of these historical processes are evident in patterns of differentiation among extant populations, which are often expressed as genetic and behavioral variation between populations. We investigated the effects of geographic barriers on the evolutionary history of a Mesoamerican bird by studying patterns of genetic and vocal variation in the Ruddy-capped Nightingale-Thrush (Turdidae: Catharus frantzii), a non-migratory oscine bird that inhabits montane forests from central Mexico to Panama. We reconstructed the phylogeographic history and estimated divergence times between populations using Bayesian and maximum likelihood methods. We found strong support for the existence of four mitochondrial lineages of C. frantzii corresponding to isolated mountain ranges: Sierra Madre Oriental; Sierra Madre del Sur; the highlands of Chiapas, Guatemala, and El Salvador; and the Talamanca Cordillera. Vocal features in C. frantzii were highly variable among the four observed clades, but vocal variation and genetic variation were uncorrelated. Song variation in C. frantzii suggests that sexual selection and cultural drift could be important factors driving song differentiation in C. frantzii., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: Changes in left ventricular (LV) function using echocardiography and cardiac magnetic resonance (CMR) imaging were assessed in a contemporary ST-segment elevation myocardial infarction (STEMI) population to assess whether repeated imaging is necessary., Methods: In a prospective study patients with first STEMI were treated with primary percutaneous coronary intervention (PCI) and examined with 2D-echocardiography and CMR at baseline (<72 h) and at a three-month follow-up., Results: A total of 138 patients were included (60±11 years). Using 2D-echocardiography at baseline preserved left ventricular ejection fraction (LVEF) (>50%) was found in 48 patients (35%), mild/moderate systolic dysfunction (35-50%) in 76 patients (55%) and severe dysfunction (<35%) in 14 patients (10%). Improvement in systolic function group was seen in 58 patients (64%) and 11 patients (79%) with severe systolic dysfunction at baseline were re-classified as having preserved or mild/moderate systolic dysfunction at follow-up. Irrespective of baseline LVEF, deterioration in systolic function group was noted in 14 patients (11%), but no patients declined from preserved to severe systolic dysfunction. The recovered myocardium measured with the myocardial salvage index by CMR was significantly lower with declining LVEF at baseline., Conclusion: The majority of patients with severely depressed LVEF immediately after STEMI significantly improved systolic function after three months. This study emphasises the importance of a repeated LV function assessment at follow-up in patients with mild/moderate or severe systolic dysfunction after STEMI, but re-assessment may not be needed in patients with preserved LVEF at baseline., (© The European Society of Cardiology 2014.)

Aims: The goal of the study was to examine the prognostic impact, haemodynamic and clinical features associated with lung congestion in patients with chronic heart failure (HF)., Methods and Results: HF patients (n = 186) and HF-free controls (n = 21) underwent right heart catheterization, echocardiography, pulmonary function testing and chest radiography that was blindly scored for the presence and severity of lung oedema. Lung congestion correlated directly with pulmonary vascular resistance (PVR, P = 0.004) and inversely with pulmonary artery (PA) compliance (P < 0.001) and the diffusion limit for carbon monoxide (DLCO , P = 0.009). Compared with dry lung HF, wet lung HF patients (congestion score > median) had 25% lower PA compliance and 25-35% higher PVR, transpulmonary gradients and PA pressures (40 vs. 32 mmHg, P < 0.001) despite marginally higher PA wedge pressure (PAWP; 22 vs. 19 mmHg, P = 0.002). Wet lung HF patients displayed more right ventricular (RV) dilatation and dysfunction, more restrictive ventilation and greater reduction of DLCO . The strongest correlates of lung congestion were NT-proBNP, haemoglobin, albumin, and glomerular filtration, all surpassing PAWP. After a median of 333 days (interquartile range 80-875), 59 patients (32%) died. Lung congestion was associated with reduced survival (P < 0.0001), even after adjusting for PAWP, NT-proBNP, anaemia, CAD and renal dysfunction., Conclusion: Interstitial lung oedema is associated with pulmonary vascular disease, RV overload and dysfunction and increased mortality in HF. These data reinforce the importance of aggressive decongestion in HF and suggest that novel agents aimed at reducing lung water may help to deter progression of pulmonary vascular disease and biventricular HF., (© 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.)

Purpose: Left atrial (LA) volume is a strong prognostic predictor in patients following ST-segment elevation myocardial infarction (STEMI). However, the change in LA volume over time (LA remodelling) following STEMI has been scarcely studied. We sought to identify predictors for LA remodelling and to evaluate the prognostic importance of LA remodelling., Methods: This is a subgroup analysis from a randomised clinical trial that evaluated the cardioprotective effect of exenatide treatment. A total of 160 patients with STEMI underwent a cardiovascular MR (CMR) 2 days after primary angioplasty and a second scan 3 months later. LA remodelling was defined as changes in LA volume or function from baseline to 3 months follow-up. Major adverse cardiac events were registered after a median of 5.2 years., Results: Adverse LA minimum volume (LAmin) remodelling was correlated to the presence of hypertension, larger infarct size by CMR, higher peak troponin T, larger area at risk and adverse left ventricular (LV) remodelling. LA maximum volume (LAmax) remodelling was correlated to larger infarct size by CMR, higher peak troponin T, larger area at risk, larger LV mass, impaired LV function and adverse LV remodelling. Kaplan-Meier and Log Rank analyses showed that patients in the highest tertiles of LAmin or LAmax remodelling are at higher risk (0.030 and p=0.018)., Conclusions: After a myocardial infarction, LA remodelling reflects a parallel ventricular-atrial remodelling. Infarct size is a major determinant of LA remodelling following STEMI and adverse LA remodelling is associated with an unfavourable prognosis.

Background: Diagnostic knee arthroscopy is a common procedure that orthopaedic residents are expected to learn early in their training. Arthroscopy requires a different skill set from traditional open surgery, and many orthopaedic residents feel less prepared for arthroscopic procedures. Virtual reality simulation training and testing provide an opportunity to ensure basic competency before proceeding to supervised procedures in patients., Methods: Twenty-six physicians (thirteen novices and thirteen experienced arthroscopic surgeons) were voluntarily recruited to perform a test consisting of five arthroscopic procedures on a knee arthroscopy simulator. Performance was evaluated by obtaining predefined metrics from the simulator for each procedure, and z-scores, describing suboptimal performance, were calculated from the metrics. The intercase reliability of the simulator metrics was explored by calculating an intraclass correlation coefficient. Finally, a pass-or-fail standard was set with use of the contrasting groups method, and the consequences of the pass-or-fail standard were explored., Results: One procedure was excluded from the final test because of a lack of validity. The total Z-scores for the four procedures included in the final test showed an intercase reliability of 0.87 (95% confidence interval, 0.78 to 0.93). The total mean z-score (and standard deviation) was 38.6 ± 27.3 points for the novices and 0.0 ± 9.1 points for the experienced surgeons (p < 0.0005). The pass-or-fail standard was set at a total z-score of 15.5 points, resulting in two of the novices passing the test and a single experienced surgeon failing the test., Conclusions: By combining four procedures on a virtual reality arthroscopy simulator, it was possible to create a valid, reliable, and feasible test of basic arthroscopic competency and to establish a credible pass-or-fail standard., Clinical Relevance: The simulation-based test and pass-or-fail standard could aid in assessing and ensuring basic competency of future orthopaedic residents before proceeding to supervised procedures in patients., (Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Pulmonary hypertension and right ventricular (RV) dysfunction are common in patients with advanced heart failure with preserved ejection fraction (HFpEF), yet their underlying mechanisms remain poorly understood. We sought to examine RV-pulmonary artery (PA) functional reserve responses and RV-PA coupling at rest and during β-adrenergic stimulation in subjects with earlier stage HFpEF., Methods and Results: In a prospective trial, subjects with HFpEF (n=39) and controls (n=18) underwent comprehensive invasive and noninvasive hemodynamic assessment using high fidelity micromanometer catheters, echocardiography, and expired gas analysis at rest and during dobutamine infusion. HFpEF subjects displayed similar RV structure but significantly impaired RV systolic (lower RV dP/dtmax/IP and s') and diastolic function (higher RV τ) coupled with more severe pulmonary vascular disease, manifest by higher PA pressures, higher PA resistance, and lower PA compliance compared with controls. Dobutamine infusion caused greater pulmonary vasodilation in HFpEF compared with controls, with enhanced reductions in PA resistance, greater increase in PA compliance, and a more negative slope in the PA pressure-flow relationship when compared with controls (all P<0.001). RV-PA coupling analysis revealed that dobutamine improved RV ejection in HFpEF subjects through afterload reduction alone, rather than through enhanced contractility, indicating RV systolic reserve dysfunction., Conclusions: Pulmonary hypertension in early stage HFpEF is related to partially reversible pulmonary vasoconstriction coupled with RV systolic and diastolic dysfunction, even in the absence of RV structural remodeling. Pulmonary vascular tone is more favorably responsive to β-adrenergic stimulation in HFpEF than controls, suggesting a potential role for β-agonists in the treatment of patients with HFpEF and pulmonary hypertension., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01418248., (© 2015 American Heart Association, Inc.)

Todiramphus chloris is the most widely distributed of the Pacific's 'great speciators'. Its 50 subspecies constitute a species complex that is distributed over 16 000 km from the Red Sea to Polynesia. We present, to our knowledge, the first comprehensive molecular phylogeny of this enigmatic radiation of kingfishers. Ten Pacific Todiramphus species are embedded within the T. chloris complex, rendering it paraphyletic. Among these is a radiation of five species from the remote islands of Eastern Polynesian, as well as the widespread migratory taxon, Todiramphus sanctus. Our results offer strong support that Pacific Todiramphus, including T. chloris, underwent an extensive range expansion and diversification less than 1 Ma. Multiple instances of secondary sympatry have accumulated in this group, despite its recent origin, including on Australia and oceanic islands in Palau, Vanuatu and the Solomon Islands. Significant ecomorphological and behavioural differences exist between secondarily sympatric lineages, which suggest that pre-mating isolating mechanisms were achieved rapidly during diversification. We found evidence for complex biogeographic patterns, including a novel phylogeographic break in the eastern Solomon Islands that separates a Northern Melanesian clade from Polynesian taxa. In light of our results, we discuss systematic relationships of Todiramphus and propose an updated taxonomy. This paper contributes to our understanding of avian diversification and assembly on islands, and to the systematics of a classically polytypic species complex.

Monarch flycatchers are a major component of Australo-Pacific and Wallacean avifaunas. To date, the family has received incomplete attention by molecular systematists who focused on subclades with minimal character and/or taxon sampling. As a result, Monarchidae taxonomy is still out-of-date, and biogeographic reconstructions have been based on poorly-resolved phylogenies, limiting their interpretation. Here, we produced a comprehensive, molecular phylogeny of the Monarchidae inferred from mitochondrial and nuclear loci using both concatenated and multilocus coalescent frameworks. We sampled 92% of the 99 recognized monarchid biological species and included deeper sampling within several phylogenetic species complexes, including Monarcha castaneiventris, Symposiachrus barbatus, and Terpsiphone rufiventer. Melampitta is identified as sister to the monarch flycatchers, which themselves comprise four major lineages. The first lineage comprises Terpsiphone and allies, the second lineage is Grallina, the third is Arses and Myiagra, and the fourth lineage comprises a diverse assemblage of genera including the "core monarchs" and the most geographically isolated groups like Chasiempis (Hawaii) and Pomarea (eastern Polynesia). Gene tree discordance was evident in Myiagra, which has implications for basal lineages in the genus (e.g., M. azureocapilla, M. hebetior, and M. alecto). Numerous genera within the core monarchs are paraphyletic, including Mayrornis and Pomarea, whereas the validity of others such as Metabolus are questionable. We recognize polytypic taxa as multiple species, including Lamprolia victoriae and Myiagra azureocapilla. In general, the topology of species complexes included short internodes that were not well resolved, owing to their rapid diversification across island archipelagos. Terpsiphone rufiventer comprises multiple lineages, including a heretofore-unappreciated West African lineage, but relationships within these rapid radiations will require extensive genomic sampling for further resolution. This study establishes a new benchmark for Monarchidae systematics and it provides an excellent framework for future work on biogeography and character evolution in a diverse Australo-Papuan radiation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Invasive hemodynamic exercise testing is commonly used in the evaluation of patients with suspected heart failure with preserved ejection fraction (HFpEF) or pulmonary hypertension. Saline loading has been suggested as an alternative provocative maneuver, but the hemodynamic changes induced by the 2 stresses have not been compared., Methods and Results: Twenty-six subjects (aged, 67±10 years; n=14 HFpEF; n=12 control) underwent right heart catheterization at rest, during supine exercise, and with acute saline loading in a prospective study. Exercise and saline each increased cardiac output and pressures in the right atrium, pulmonary artery, and pulmonary capillary wedge positions. Changes in heart rate, blood pressure, rate-pressure product, and cardiac output were greater with exercise compared with saline. In controls subjects, right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure increased similarly with saline and exercise, whereas in HFpEF subjects, exercise led to ≈2-fold greater increases in right atrial pressure (10±4 versus 6±3 mm Hg; P=0.02), pulmonary arterial pressure (22±8 versus 11±4 mm Hg; P=0.0001), and pulmonary capillary wedge pressure (18±5 versus 10±4 mm Hg; P<0.0001) compared with saline. Systolic reserve assessed by stroke work and cardiac power output was lower in HFpEF subjects with both exercise and saline. Systemic and pulmonary arterial compliances were enhanced with saline but reduced with exercise., Conclusions: Exercise elicits greater pulmonary capillary wedge pressure elevation compared with saline in HFpEF but not controls, suggesting that hemodynamic stresses beyond passive stiffness and increased venous return explain the development of pulmonary venous hypertension in HFpEF. Exercise testing is more sensitive than saline loading to detect hemodynamic derangements indicative of HFpEF., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01418248., (© 2014 American Heart Association, Inc.)

The Golden Whistler (Aves: Passeriformes: Pachycephalidae) Pachycephala pectoralis sensu lato has long played a key role in the development of the theory of allopatric speciation (Mayr 1932a, b; Mayr 1942; Galbraith 1956). The P. pectoralis species complex formerly comprised 60-70 nominal subspecies and so had a distribution spanning the Indo-Pacific (Boles 2007). More recent taxonomic treatments consider the complex as multiple species-level taxa largely circumscribed by geography (Dickinson and Christidis 2014; Gill and Donsker 2014). In Australia, the endemic species P. pectoralis sensu stricto is sympatric with the closely related Mangrove Golden Whistler P. melanura. However, as the latter's English name suggests, P. melanura is closely tied to mangroves in Australia, southeast New Guinea, and islets in the Bismarck Archipelago. Diagnostic plumage traits separating the two species are subtle: males of P. melanura have more extensively black tails and a greyer upper surface to the remiges, and females are usually yellower ventrally. All Pachycephala species, especially those in the P. pectoralis-melanura species complex, have recently become the focus of DNA sequence-based studies (Jønsson et al. 2008, 2014; Andersen et al. 2014). Data from most populations have now been analysed phylogenetically to better understand relationships and thus the history of evolution and speciation processes within and between both species. This has also been used in studies of the group's historical biogeography to provide information as to the age of taxa and their spread across oceanic archipelagos and continents (Jønsson et al. 2014). Here we discuss the taxonomic implications of a result that has emerged consistently and independently in these studies, concerning the systematics of the southern Australian populations in south-eastern and south-western Australia, both of which have been ascribed to P. p. fuliginosa since Galbraith (1956), and we show that the name P. occidentalis Ramsay, 1878 is available for the western population and should be used for it.

Background: Increased pulmonary capillary wedge pressure (PCWP) is an independent prognostic predictor after myocardial infarction (MI), but PCWP is difficult to assess noninvasively in subjects with preserved ejection fraction (EF). We hypothesized that biomarkers would provide information regarding PCWP at rest and during exercise in subjects with preserved EF after MI., Methods and Results: Seventy-four subjects with EF >45% and recent MI underwent right heart catheterization at rest and during a symptom-limited semisupine cycle exercise test with simultaneous echocardiography. Plasma samples were collected at rest for assessment of midregional pro-A-type natriuretic peptide (MR-proANP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), copeptin, and midregional pro-adrenomedullin (MR-proADM). Plasma levels of MR-proANP and PCWP were associated at rest (r = 0.33; P = .002) and peak exercise (r = 0.35; P = .002) as well as with changes in PCWP (r = 0.26; P = .03). Plasma levels of NT-proBNP and PCWP were weakly associated at rest (r = 0.23; P = .03) and peak exercise (r = 0.28; P = .02) but not with changes in PCWP (r = 0.20; P = .09). In a multivariable analysis, plasma levels of MR-proANP remained associated with rest and exercise PCWP (P < .01), whereas NT-proBNP did not. Plasma levels of Gal-3, copeptin, and MR-proADM were not associated with PCWP at rest or peak exercise., Conclusions: In subjects recovering from an acute MI with preserved EF, plasma levels of natriuretic peptides, particularly MR-proANP, are associated with filling pressures at rest and during exercise., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Patients with severe tricuspid regurgitation (TR) frequently present with exertional fatigue and dyspnea, but the hemodynamic basis for exercise limitation in people with TR remains unclear., Methods and Results: Twelve subjects with normal left ventricular (LV) ejection fraction and grade ≥3 TR underwent high-fidelity invasive hemodynamic exercise testing with simultaneous expired gas analysis and were compared with 13 age- and sex-matched controls. At rest, TR subjects had lower pulmonary blood flow (3.6±0.4 versus 5.1±1.9 L/min; P=0.01), increased right atrial pressure (12±5 versus 4±1 mm Hg; P=0.0002), and higher pulmonary capillary wedge pressure (17±5 versus 9±3 mm Hg; P=0.0001). However, LV transmural pressure (pulmonary capillary wedge pressure-right atrial pressure), which reflects LV preload independent of right heart congestion and pericardial restraint, was similar in TR and controls (6±3 versus 4±2 mm Hg; P=0.3). With exercise, TR subjects displayed lower peak VO2 (10.3±2.8 versus 13.8±4.2 mL/min per kg; P=0.02), lower pulmonary blood flow (6.4±1.3 versus 10.3±3.3 L/min; P=0.001), and less increase in pulmonary blood flow relative to VO2 (+4.6±1.1vs +6.2±0.7; P=0.001). TR subjects displayed higher pulmonary capillary wedge pressure with exercise, but this was solely because of RA hypertension (27±9 versus 8±3 mm Hg; P<0.0001), because LV transmural pressure dropped with exercise in subjects with TR (-5±6 versus +3±3 mm Hg; P=0.0007), suggesting inadequate LV diastolic filling, despite high pulmonary capillary wedge pressure., Conclusions: Impaired exercise capacity in people with severe TR is related to low cardiac output reserve relative to metabolic needs, coupled with elevated systemic and pulmonary venous pressures. Left heart pressures are elevated with exercise in subjects with TR, despite low LV preload, secondary to enhanced ventricular interaction., (© 2014 American Heart Association, Inc.)

Recent hemodynamic studies have advanced our understanding of heart failure with preserved ejection fraction (HFpEF). Despite improved pathophysiologic insight, clinical trials have failed to identify an effective treatment for HFpEF. Invasive hemodynamic assessment can diagnose or exclude HFpEF, making it invaluable in understanding the basis of the disease. This article reviews the hemodynamic mechanisms underlying HFpEF and how they manifest clinically, discusses invasive hemodynamic assessment as a diagnostic tool, and explores how invasive hemodynamic profiling may allow understanding of pathophysiological differences and inform the design and entry criteria for future trials., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Heart failure (HF) is the leading cause of hospitalization among older adults and the prevalence is growing with the aging populations in western countries. Approximately one-half of patients with HF have preserved ejection fraction (HFpEF). In contrast to HF with reduced EF (HFrEF), there is no proven effective treatment for HFpEF. The pathophysiology of HFpEF is complex, and the dominant mechanisms leading to symptoms of HF often vary between afflicted patients, confounding efforts to apply "one-size fits all" types of therapeutic approaches. Current treatment strategies focus on control of volume status and comorbidities, but future research aimed at individualized therapies holds promise to improve outcomes in this increasingly prevalent form of cardiac failure.

Introduction: The importance of supervision and of surgeons' level of experience in relation to patient outcome have been demonstrated in both hip fracture and arthroplasty surgery. The aim of this study was to describe the surgeons' experience level and the extent of supervision for: 1) fracture-related surgery in general; 2) the three most frequent primary operations and reoperations; and 3) primary operations during and outside regular working hours., Material and Methods: A total of 9,767 surgical procedures were identified from the Danish Fracture Database (DFDB). Procedures were grouped based on the surgeons' level of experience, extent of supervision, type (primary, planned secondary or reoperation), classification (AO Müller), and whether they were performed during or outside regular hours., Results: Interns and junior residents combined performed 46% of all procedures. A total of 90% of surgeries by interns were performed under supervision, whereas 32% of operations by junior residents were unsupervised. Supervision was absent in 14-16% and 22-33% of the three most frequent primary procedures and reoperations when performed by interns and junior residents, respectively. The proportion of unsupervised procedures by junior residents grew from 30% during to 40% (p < 0.001) outside regular hours., Conclusion: Interns and junior residents together performed almost half of all fracture-related surgery. The extent of supervision was generally high; however, a third of the primary procedures performed by junior residents were unsupervised. The extent of unsupervised surgery performed by junior residents was significantly higher outside regular hours., Funding: not relevant., Trial Registration: The Danish Fracture Database ("Dansk Frakturdatabase") was approved by the Danish Data Protection Agency ID: 01321.

Aims: Diastolic dysfunction in acute myocardial infarction (MI) is associated with adverse outcome. Recently, the ratio of early mitral inflow velocity (E) to global diastolic strain rate (e'sr) has been proposed as a marker of elevated LV filling pressure. However, the prognostic value of this measure has not been demonstrated in a large-scale setting when existing parameters of diastolic function are known. We hypothesized that the E/e'sr ratio would be independently associated with an adverse outcome in patients with MI., Methods and Results: We prospectively included patients with MI and performed echocardiography with comprehensive diastolic evaluation including E/e'sr. The relationship between E/e'sr and the primary composite endpoint (all-cause mortality, hospitalization for heart failure (HF), stroke, and new onset atrial fibrillation) was analysed with Cox models. A total of 1048 patients (mean age 63 ± 12, 73% male) were included and 142 patients (13.5%) reached the primary endpoint (median follow-up 29 months). A significant prognostic value was found for E/e'sr [hazard ratio (HR) per 1 unit change: 2.36, 95% confidence interval (CI): 2.02-2.75, P < 0.0001]. After multivariable adjustment E/e'sr remained independently related to the combined endpoint (HR per 1 unit change, 1.50; CI: 1.05-2.13, P = 0.02). The prognostic value of E/e'sr was driven by mortality (HR per 1 unit change, 2.52; CI: 2.09-3.04, P < 0.0001) and HF admissions (HR per 1 unit change, 2.79; CI: 2.23-3.48, P < 0.0001)., Conclusion: Deformation-based E/e'sr contributes important information about global myocardial relaxation superior to velocity-based analysis and is independently associated with the outcome in acute MI.

We investigated the molecular phylogenetic placement of 14 species of Pacific island honeyeaters (Aves: Meliphagidae) in the broader context of an existing family-level phylogeny. We examined the evolutionary history of Pacific honeyeater lineages to assess the accuracy of current taxonomies and to evaluate their biogeographic history. We compare these biogeographic patterns to other Pacific birds to identify emergent patterns across lineages. We found strong support for a previously unknown endemic radiation in central Polynesia, which comprises five genera: Meliarchus, Guadalcanaria, Gymnomyza, Xanthotis, and Foulehaio. Conversely, other Pacific lineages were found to be strongly allied with continental radiations (e.g., Philemon eichhorni, P. cockerelli, and Lichmera incana). Our results necessitated taxonomic changes, both at the generic level (e.g., Xanthotis, Melidectes/Vosea, and Glycifohia/Gliciphila) and regarding species limits within polytypic species. Here, we discuss species limits in Foulehaio and Gymnomyza and recommend elevating three nominal subspecies of Foulehaio to species status, each of which forms well-differentiated clades., (Copyright © 2013 Elsevier Inc. All rights reserved.)

To evaluate the diagnostic accuracy of aortic valve area (AVA) assessment with 320-detector Computed Tomography (MDCT) compared to transthoracic echocardiography (TTE) in a population with mild to severe aortic valve stenosis. AVA was estimated in 169 patients by planimetry on MDCT images (AVA(MDCT)) and by the continuity equation with TTE (AVA(TTE)). To generate a reference AVA (AVA(REF)) we used the stroke volume from MDCT divided by the velocity time integral from CW Doppler by TTE (according to the continuity equation: stroke volume in LVOT = stroke volume passing the aortic valve). AVA(REF) was used as the reference to compare both measures against, since it bypasses the assumption of LVOT being circular in the continuity equation and the potential placement error of PW Doppler in the LVOT. The mean (±SD) age of the patients was 71 (±9) years, 113 (67%) were males. Mean AVA(TTE) was 0.93 (±0.33) cm(2), mean AVA(MDCT) was 0.99 (±0.36) cm(2) and mean AVA(REF) was 1.00 (±0.39) cm(2). The mean difference between AVA(TTE) and AVA(MDCT) was -0.06 cm(2), p = 0.001, mean difference between AVA(TTE) and AVA(REF) was -0.06 cm(2), p < 0.001, and mean difference between AVA(MDCT) and AVA(REF) was -0.01 cm(2), p = 0.60. Calcification of the aortic valve quantified by Agatston score, significantly decreased the correlation between AVA(MDCT) and AVA(REF), (r low Agatston = 0.90, r high Agatston = 0.57). MDCT measured AVA is slightly larger than AVA measured by TTE (0.06 cm(2)). The accuracy and precision errors on AVA measurements are comparable for MDCT and TTE. Valvular calcification may primarily affect the accuracy of AVA(MDCT).

Background: To assess whether changes in E/e´ (the ratio between peak early mitral inflow velocity (E) and peak early mitral annulus velocity (e´)) during exercise reflect changes in filling pressure in patients with a recent myocardial infarction (MI) and mild to moderate diastolic dysfunction at rest. A low E/e´ ratio is associated with low filling pressures while a high E/e´ ratio is associated with high filling pressures. In the intermediate range of E/e´ guidelines suggest additional measurements during exercise in order to determine filling pressures., Methods and Results: Sixty-one patients with a recent MI and left ventricular ejection fraction (LVEF) ≥ 45%, left atrium (LA)>34 ml/m(2) and E/e´ between 8 and 15, underwent simultaneous right heart catheterization and Doppler echocardiography during a symptom limited semi supine cycle exercise test. E velocity increased from 75 ± 16 to 139 ± 27 cm/s and e´ increased from 7.1 ± 1.4 to 16.1 ± 3.6 cm/s with exercise. Thus, E/e´ decreased from 10.5 ± 1.7 to 9.3 ± 2.3 while pulmonary capillary wedge pressure (PCWP) increased from 13 ± 4 to 33 ± 8 mmHg. There was no correlation between LV filling pressure and E/e´ at rest, at 4 METS, at peak exercise or 5 min after termination of exercise. Neither was there any correlation between changes in PCWP and changes in E/e´., Conclusion: For post-MI patients with resting E/e´ in the intermediate range changes in E/e´ with physical exercise does not reflect changes in LV filling pressures., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study sought to hypothesize that global longitudinal strain (GLS) as a measure of infarct size, and mechanical dispersion (MD) as a measure of myocardial deformation heterogeneity, would be of incremental importance for the prediction of sudden cardiac death (SCD) or malignant ventricular arrhythmias (VA) after acute myocardial infarction (MI)., Background: SCD after acute MI is a rare but potentially preventable late complication predominantly caused by malignant VA. Novel echocardiographic parameters such as GLS and MD have previously been shown to identify patients with chronic ischemic heart failure at increased risk for arrhythmic events. Risk prediction during admission for acute MI is important because a majority of SCD events occur in the early period after hospital discharge., Methods: We prospectively included patients with acute MI and performed echocardiography, with measurements of GLS and MD defined as the standard deviation of time to peak negative strain in all myocardial segments. The primary composite endpoint (SCD, admission with VA, or appropriate therapy from a primary prophylactic implantable cardioverter-defibrillator [ICD]) was analyzed with Cox models., Results: A total of 988 patients (mean age: 62.6 ± 12.1 years; 72% male) were included, of whom 34 (3.4%) experienced the primary composite outcome (median follow-up: 29.7 months). GLS (hazard ratio [HR]: 1.38; 95% confidence interval [CI]: 1.25 to 1.53; p < 0.0001) and MD (HR/10 ms: 1.38; 95% CI: 1.24 to 1.55; p < 0.0001) were significantly related to the primary endpoint., Gls (hr: 1.24; 95% CI: 1.10 to 1.40; p = 0.0004) and MD (HR/10 ms: 1.15; 95% CI: 1.01 to 1.31; p = 0.0320) remained independently prognostic after multivariate adjustment. Integrated diagnostic improvement (IDI) and net reclassification index (NRI) were significant for the addition of GLS (IDI: 4.4% [p < 0.05]; NRI: 29.6% [p < 0.05]), whereas MD did not improve risk reclassification when GLS was known., Conclusions: Both GLS and MD were significantly and independently related to SCD/VA in these patients with acute MI and, in particular, GLS improved risk stratification above and beyond existing risk factors., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate whether left ventricular (LV) systolic shortening velocity (s'), diastolic lengthening velocity (e'), and non-invasively estimated LV filling pressure (E/e') during low-dose dobutamine echocardiography (LDDE) reflect invasive measures of cardiac output and pulmonary capillary wedge pressure (PCWP) in stable patients with chronic systolic heart failure., Methods and Results: Fourteen patients with heart failure (aged 65 ± 8 years, LVEF 36 ± 8%) underwent simultaneous tissue Doppler echocardiography and invasive measurements of cardiac output and PCWP by right heart catheterization at rest and during dobutamine infusion at rates of 10 and 20 µg/kg/min. Cardiac output increased from rest to peak dobutamine (4.9 ± 1.2 to 6.6 ± 2.0 L/min, P < 0.001) and correlated with the peak systolic tissue velocity (s') at rest (R = 0.61, P = 0.02) and during dobutamine stimulation (R = 0.79, P < 0.001). Increases in early diastolic mitral inflow (E, 74.9 ± 29.0-90.8 ± 29.5 cm/s) and LV lengthening (e', 6.5 ± 2.4-8.2 ± 2.8 cm/s) velocities were observed during LDDE leaving the E/e' ratio unchanged. Although a mean PCWP was also unchanged from rest to peak dobutamine (16.6 ± 8.3-14.2 ± 9.2, P = 0.25), E/e' and PCWP only correlated at rest (R = 0.64, P = 0.014)., Conclusion: The LV systolic shortening velocity is closely associated with cardiac output during LDDE in CHF patients. Dobutamine stimulation increases early diastolic mitral inflow and lengthening velocities, but the E/e' ratio does not reflect the PCWP during LDDE, which warrants some caution in converting changes in E/e' into changes in LV filling pressure. The sample size is, however, small and the observation need to be confirmed in a larger population.

Nephrologists in the United States face a very uncertain economic future. The astronomical federal debt and unfunded liability burden of Medicare combined with the aging population will place unprecedented strain on the health care sector. To address these fundamental problems, it is conceivable that the federal government will ultimately institute rationing and other budget-cutting measures to rein in costs of ESRD care, which is generously funded relative to other chronic illnesses. Therefore, nephrologists should expect implementation of cost-cutting measures, such age-based rationing, mandated delayed dialysis and home therapies, compensated organ donation, and a shift in research priorities from the dialysis to the predialysis patient population. Nephrologists also need to recognize that these changes, which are geared toward the population level, may make it more difficult to advocate effectively for the needs of individual patients.

Objectives: This study sought to test the hypothesis that semiautomated calculation of left ventricular global longitudinal strain (GLS) can identify high-risk subjects among patients with myocardial infarctions (MIs) with left ventricular ejection fractions (LVEFs) >40%., Background: LVEF is a key determinant in decision making after acute MI, yet it is relatively indiscriminant within the normal range. Novel echocardiographic deformation parameters may be of particular clinical relevance in patients with relatively preserved LVEFs., Methods: Patients with MIs and LVEFs >40% within 48 h of admission for coronary angiography were prospectively included. All patients underwent echocardiography with semiautomated measurement of GLS. The primary composite endpoint (all-cause mortality and hospitalization for heart failure) was analyzed using Cox regression analyses. The secondary endpoints were cardiac death and heart failure hospitalization., Results: A total of 849 patients (mean age 61.9 ± 12.0 years, 73% men) were included, and 57 (6.7%) reached the primary endpoint (median follow-up 30 months). Significant prognostic value was found for GLS (hazard ratio [HR]: 1.20; 95% confidence interval [CI]: 1.10 to 1.32; p < 0.001). GLS > -14% was associated with a 3-fold increase in risk for the combined endpoint (HR: 3.21; 95% CI: 1.82 to 5.67; p < 0.001). After adjustment for other variables, GLS remained independently related to the combined endpoint (HR: 1.14; 95% CI: 1.04 to 1.26; p = 0.007). For the secondary endpoints, GLS > -14% was significantly associated with cardiovascular death (HR: 12.7; 95% CI: 3.0 to 54.6; p < 0.001) and heart failure hospitalization (HR: 5.31; 95% CI: 1.50 to 18.82; p < 0.001)., Conclusions: Assessment of GLS using a semiautomated algorithm provides important prognostic information in patients with LVEFs >40% above and beyond traditional indexes of high-risk MI., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Diastolic dysfunction following myocardial infarction is an important predictor of outcome, irrespective of left ventricular systolic function. Previous studies suggest that phosphordiesterase-5 inhibition has a favorable effect on the myocardium as well as on the pulmonary and systemic vasculature., Methods: Patients≥50 years old with recent myocardial infarction, preserved left ventricular ejection fraction (≥45%), and echocardiographic evidence of diastolic dysfunction (ratio between early [E] transmitral filling velocity and early diastolic tissue Doppler velocity [e']≥8 and left atrial volume≥34 mL/m2) will be double-blindly randomized 1:1 to receive 9 weeks of treatment with 40 mg sildenafil, 3 times per day, or comparable placebo. Before randomization and after 9 weeks of treatment, resting Doppler echocardiography, resting right heart catheterization, and symptom-limited supine cycle exercise testing with simultaneous echocardiography and right heart catheterization will be performed. The primary end point is filling pressure at rest and at peak exercise., Statistics: With a power of 80% and a significance level of .05, a study group of 60 patients is needed to detect a 15% reduction at peak exercise, which is considered clinically relevant. To account for dropouts and noncompliance, 70 patients will be enrolled in the study., Conclusions: In addition to determining if sildenafil can reduce filling pressure at rest and at peak exercise, the Sildenafil and Diastolic Dysfunction After Acute Myocardial Infarction trial will provide additional hemodynamic information to help phenotypically classify this growing population of patients with diastolic dysfunction and preserved ejection fraction following myocardial infarction., (© 2013 Wiley Periodicals, Inc.)

Background: Diastolic dysfunction is frequently seen after myocardial infarction and is characterized by a disproportionate increase in filling pressure during exercise to maintain stroke volume. We hypothesized that sildenafil would reduce filling pressure during exercise in patients with diastolic dysfunction after myocardial infarction., Methods and Results: Seventy patients with diastolic dysfunction and near normal left ventricular ejection fraction on echocardiography were randomly assigned sildenafil 40 mg thrice daily or matching placebo for 9 weeks. Before randomization and after 9 weeks of treatment patients underwent simultaneous echocardiography and right heart catheterization at rest and during exercise. Primary end point was pulmonary capillary wedge pressure, and secondary end points comprised cardiac index and pulmonary arterial pressure at rest and during exercise after 9 weeks. After 9 weeks there were no differences in pulmonary capillary wedge pressure at rest (13±4 versus 13±3 mm Hg, P=0.25) or at peak exercise (35±8 mm Hg versus 31±7 mm Hg, P=0.07). However, with treatment cardiac index increased at rest (P=0.006) and peak exercise (P=0.02) in the sildenafil group, and systemic vascular resistance index (resting, P=0.0002; peak exercise, P=0.007) and diastolic blood pressure (resting, P=0.005; peak exercise, P=0.02) were lower in the sildenafil group. Resting left ventricular end-diastolic volume index increased (P=0.001) within the sildenafil group but was unchanged in the placebo group., Conclusions: Sildenafil did not decrease filling pressure at rest or during exercise in post-myocardial infarction patients with diastolic dysfunction. However, there were effects on secondary end points, which require further studies.

Phylogenetic analyses of nuclear and mitochondrial DNA sequences were used to test a recent phylogenetic hypothesis for the avian genus Gallicolumba that relied heavily on preserved museum study skins for DNA samples. Our comparisons show that several published gene sequences represent pseudogenes or chimeras of multiple taxa, and these sequences had an adverse influence on phylogeny estimation. A new phylogenetic hypothesis strongly supports the monophyly of Philippine bleeding-hearts, the monophyly of Gallicolumba sensu stricto, and places Leucosarcia as part of an Australasian radiation rather than sister to Alopecoenas. These findings clarify Gallicolumba biogeography and also highlight the need for greater caution in the use of suboptimal source material in molecular systematic studies., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Peak atrial longitudinal strain (PALS) during the reservoir phase has been proposed as a measure of left atrium function in a range of cardiac conditions, with the potential for added pathophysiological insight and prognostic value. However, no studies have assessed the interrelation of PALS and left ventricular longitudinal strain (global longitudinal strain) in large-scale populations in regard to prognosis., Methods and Results: We prospectively included 843 patients (mean age 62.1±11.8; 74% male) with acute myocardial infarction and measured global longitudinal strain, left atrium volumes, and PALS within 48 hours of admission. PALS was related to a composite outcome of death and heart failure hospitalization. Reduced PALS was associated with hypertension, diabetes mellitus, and Killip class >1 (P<0.05 for all). Reduced PALS was associated with impairment of all measures of left ventricular systolic and diastolic function, and the correlation between global longitudinal strain and PALS was highly significant (P<0.001; r=-0.71). During follow-up (median 23.0 months Q1-Q3, 16.8-26.0), a total of 76 patients (9.0%) reached the composite end point of which 47 patients died (5.6%), and 29 patients were hospitalized for heart failure (3.4%). PALS was significantly associated with outcome (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.85-0.90; P<0.001); however, no independent effect of PALS (HR, 1.00; 95% CI, 0.94-1.05; P=0.87) was found when adjusting for global longitudinal strain (HR, 1.20; 95% CI, 1.09-1.33; P<0.001), maximum left atrium volume before mitral valve opening (HR, 1.02; 95% CI, 1.01-1.04; P=0.006), and age (HR, 1.06; 95% CI, 1.03-1.08; P<0.001)., Conclusions: PALS provides a composite measure of left ventricular longitudinal systolic function and maximum left atrium volume before mitral valve opening, and as such contains no added information when these readily obtained measures are known.

Background: Heart failure (HF) complicating acute myocardial infarction (MI) is an ominous prognostic sign frequently caused by left ventricular (LV) systolic dysfunction. However, many patients develop HF despite preserved LV ejection fractions. The aim of this study was to test the hypothesis that LV longitudinal function is a stronger marker of in-hospital HF than traditional echocardiographic indices., Methods: A total of 548 patients with acute MIs were evaluated (mean age, 63.2 ± 11.7 years; 71.6% men). Within 48 hours of admission, comprehensive echocardiography with assessment of global longitudinal strain (GLS) was performed, along with measurements of N-terminal pro-brain natriuretic peptide., Results: A total 89 patients (16.2%) had in-hospital HF assessed by Killip class > 1 in whom GLS was significantly impaired compared with patients without in-hospital HF (Killip class 1) (-14.6 ± 3.3% vs -10.1 ± 3.5%, P < .0001). In stepwise multiple logistic regression analysis including age, known HF, three-vessel disease, involvement of the left anterior descending coronary artery, episodes of atrial fibrillation, renal function, N-terminal pro-brain natriuretic peptide, troponin T level, LV ejection fraction, wall motion score index, and diastolic dysfunction indices, GLS emerged as the strongest marker of clinical HF (odds ratio, 1.47; 95% confidence interval [CI], 1.33-1.62; P < .0001). GLS remained independently associated with in-hospital HF in patients with LV ejection fractions > 40% (odds ratio, 1.33; 95% CI, 1.14-1.54; P < .05) and improved the C-statistic over other important covariates significantly (0.87 [95% CI, 0.82-0.91] vs 0.82 [95% CI, 0.76-0.89], P = .02)., Conclusions: Global longitudinal function assessed by GLS is significantly impaired in patients with MIs with in-hospital HF, and multivariate analysis suggests that reduced GLS is the single most powerful marker of manifest LV hemodynamic deterioration in the acute phase of MI., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

The avian family Timaliidae is a species rich and morphologically diverse component of African and Asian tropical forests. The morphological diversity within the family has attracted interest from ecologists and evolutionary biologists, but systematists have long suspected that this diversity might also mislead taxonomy, and recent molecular phylogenetic work has supported this hypothesis. We produced and analyzed a data set of 6 genes and almost 300 individuals to assess the evolutionary history of the family. Although phylogenetic analysis required extensive adjustment of program settings, we ultimately produced a well-resolved phylogeny for the family. The resulting phylogeny provided strong support for major subclades within the family but extensive paraphyly of genera. Only 3 genera represented by more than 3 species were monophyletic. Biogeographic reconstruction indicated a mainland Asian origin for the family and most major clades. Colonization of Africa, Sundaland, and the Philippines occurred relatively late in the family's history and was mostly unidirectional. Several putative babbler genera, such as Robsonius, Malia, Leonardina, and Micromacronus are only distantly related to the Timaliidae.

Background: Left ventricular diastolic dysfunction (DD) is common after myocardial infarction (MI) despite preservation of left ventricular ejection fraction, yet it remains unclear how or whether DD affects cardiac hemodynamics with stress., Methods and Results: Invasive hemodynamic exercise testing was performed in 46 patients with a recent MI and left ventricular ejection fraction >45% and in 10 healthy volunteers. MI patients were enrolled prospectively and divided into those with DD (MI+DD; left atrial volume index >34 mL/m(2) and diastolic E/e' ratio>8; n=35) and those without DD (MI-DD; left atrial volume index <34 mL/m(2) and E/e' ratio<8; n=11). All underwent a supine cycle ergometer test with simultaneous right heart catheterization and echocardiography. At rest, 10 patients in MI+DD (29%) had pulmonary capillary wedge pressure >15 (14±4 mm Hg), whereas none of the MI-DD (10±2 mm Hg) or controls (9±2 mm Hg) displayed pulmonary capillary wedge pressure elevation (P=0.03). During exercise, an abnormal rise in pulmonary capillary wedge pressure (>25 mm Hg) was observed in 94% of MI+DD (36±6 mm Hg) compared with 36% of MI-DD (24±6 mm Hg) and none of the controls (16±6 mm Hg; P<0.0001). Exercise right atrial pressure was the highest in MI+DD followed by MI-DD and control (15±5 versus 9±4 versus 7±5 mm Hg; P<0.001), whereas no difference in cardiac index was found between groups., Conclusions: In post-MI patients with preserved ejection fraction and left ventricular DD, cardiac output with exercise is maintained at the expense of substantially increased filling pressure. DD and loss of diastolic reserve may promote progression from stage B to stage C heart failure after MI.

Measurement of left atrial (LA) maximal volume (LA(max)) using two-dimensional transthoracic echocardiography (TTE) provides prognostic information in several cardiac diseases. However, the relationship between LA(max) and LA function is poorly understood and TTE is less well suited for measuring dynamic LA volume changes. Conversely, cardiac magnetic resonance imaging (CMR) and multi-slice computed tomography (MSCT) appears more appropriate for such measures. We sought to determine the relationship between LA size assessed with TTE and LA size and function assessed with CMR and MSCT. Fifty-four patients were examined 3 months post myocardial infarction with echocardiography, CMR and MSCT. Left atrial volumes and LA reservoir function were assessed by TTE. LA time-volume curves were determined and LA reservoir function (cyclic change and fractional change), passive emptying function (reservoir volume) and pump function (left atrial ejection fraction-LAEF) were derived using CMR and MSCT. Left atrial fractional change and left atrial ejection fraction (LAEF) determined with CMR and MSCT were unrelated to LA(max) enlargement by echocardiography (P = NS). There was an overall good agreement between CMR and MSCT, with a small to moderate bias in LA(max) (4.9 ± 10.4 ml), CC (3.1 ± 9.1 ml) and reservoir volume (3.4 ± 9.1 ml). TTE underestimates LA(max) with up to 32% compared with CMR and MSCT (P < 0.001). Left atrial function assessed with MSCT and CMR as LA fractional change and LAEF is not significantly related to LA(max) measured by TTE. TTE systematically underestimated LA volumes, whereas there are good agreements between MSCT and CMR for volumetric and functional properties.

The past two decades have seen major outbreaks of influenza viruses and flaviviruses that are spread at least in part by migratory birds. Although much new information has accumulated on the natural history of the viruses, and on the geography of migration by individual bird species, no synthesis has been achieved regarding likely patterns of spread of such pathogens by migratory birds, which constitutes a large-scale challenge in understanding the geography of bird migration. We here present a first step in this direction: a summary of seasonal (breeding, wintering) distributions of all 392 North American bird species that show marked seasonal migratory movements and that meet a series of conditions for inclusion in our analyses. We use species-level interseasonal connectivity among distributional areas to make initial forecasts of patterns of spread of bird-borne diseases via bird migration. We identify key next steps towards improved forecasting of spread patterns of bird-borne pathogens in North America, which will require substantial improvements in knowledge of the geography of bird migration., (Copyright © 2009 Elsevier B.V. All rights reserved.)

Background: Blood pressure (BP) measurements obtained outside the dialysis unit are prognostically superior. Whether it is the greater number of measurements made outside the dialysis unit that correlates with prognosis or whether BPs outside dialysis units are ecologically more valid is unknown., Methods and Results: A prospective cohort study was conducted in 133 patients on chronic hemodialysis. BP was measured by the patients at home for 1 week, over an interdialytic interval by ambulatory recording, and by 'routine' and standardized methods in the dialysis unit for 2 weeks. Up to 6 BPs were randomly selected from a 44-hour recording of ambulatory or 1-week recording of home BPs, such that the dialysis unit BPs were exactly matched to the number of ambulatory or home BPs. The relationship with left ventricular hypertrophy and all-cause mortality was analyzed using receiver-operating characteristic curves and Cox proportional hazards analysis, respectively. Over a median follow-up of 24 months, 46 patients (31%) died. A BP change of 10/5 mm Hg increased the risk of all-cause mortality by 1.22 (95% CI 1.07-1.38)/1.18 (95% CI 1.05-1.31) with the average of the 44-hour recording and 1.20 (95% CI 1.07-1.34)/1.15 (95% CI 1.03-1.27) when up to 6 random BPs from the same ambulatory recording were drawn and averaged. With home BPs the hazard ratios were 1.17/1.15 per 10/5 mm Hg increase in BP with the average of 1-week recording and 1.18/1.13 when up to 6 random BPs were drawn and averaged. Limited duration ambulatory BP monitoring of any 6-hour interval during the first 24 h or 4-day home BP recorded after the midweek dialysis was similarly predictive of all-cause mortality., Conclusions: In patients on hemodialysis, the location, not the quantity, of the BP recordings obtained outside the dialysis unit is associated with target organ damage and mortality., (2007 S. Karger AG, Basel)

Background and Objectives: Volume control is a key component of treatment of hemodialysis patients. The role of pedal edema as a marker of volume is unknown. The objective of this study was to determine factors that are associated with edema., Design, Setting, Participants, & Measurements: A cross-sectional study of asymptomatic hemodialysis patients (n = 146) in four university-affiliated hemodialysis units was conducted. Echocardiographic variables, blood volume monitoring, plasma volume markers (plasma renin and aldosterone and N-terminal pro B-type natriuretic peptide), and inflammation markers (C-reactive protein and IL-6) were measured as exposures, and edema was measured as outcome., Results: In a multivariate logistic regression analysis, age, body mass index, and left ventricular hypertrophy were independent determinants of edema. Compared with patients with normal or low weight, overweight patients had odds ratio for edema of 5.7 (95% confidence interval [CI] 1.0 to 31.8), and obese patients of 44.8 (95% CI 9.0 to 223). Patients in the top quartile of left ventricular mass index and normal to low weight had odds ratio of edema of 7.7 (95% CI 2.3 -25.9), those who were overweight of 43.5 (95% CI 3.9 to 479.8), and those who were obese of 344.8 (95% CI 33.8 to 3515). Inferior vena cava diameter, blood volume monitoring, plasma volume markers, and inflammation markers were not determinants of edema., Conclusions: Pedal edema correlates with cardiovascular risk factors such as age, body mass index, and left ventricular mass but does not reflect volume in hemodialysis patients.

Ambulatory systolic blood pressure (BP) correlates better with risk factors for progression of chronic kidney disease (CKD) compared to clinic measured BP, but its role in predicting end-stage renal disease (ESRD) and death in patients with CKD is unknown. In a cohort study of 217 Veterans with CKD BP was measured by ambulatory monitoring and in the clinic. Twenty-four hour ambulatory BP was 133.5 +/- 16.6/73.1 +/- 11.1 mm Hg and clinic BP was 155.2 +/- 25.6/84.7 +/- 14.2 mm Hg. The composite renal end point of ESRD or death over a median follow-up of 3.5 years occurred in 75 patients (34.5%), death occurred in 52 patients (24.0%), and ESRD in 36/178 patients (20.2%). Thirty-nine patients died before reaching ESRD. One standard deviation (s.d.) increase in systolic BP increased the risk of composite outcome to 1.69 (95% confidence interval (CI) 1.32-2.17) for standard clinic measurement and to 1.88 (95% CI 1.48-2.39) for 24 h ambulatory BP recording. One s.d. increase in 24 h ambulatory systolic BP increased the risk of ESRD to 3.04 (95% CI 2.13-4.35) and to 2.20 (95% CI 1.43-3.39) when adjusted for standard clinic systolic BP. Non-dipping was associated with increased risk of total mortality and composite end point. In patients with CKD, BPs obtained by ambulatory monitoring are a stronger predictor of ESRD or death compared to BPs obtained in the clinic. Systolic ambulatory BP and nondipping are independent predictors for ESRD after adjusting for clinic BP. However, adjustment for other risk factors for CKD progression removes the independent prognostic value of ambulatory BP.

Using interdialytic ambulatory blood pressure (BP) recordings as the reference standard, we compared the performance of routine, standardized and home BP monitoring in 104 predominantly black patients on chronic hemodialysis for at least 3 months. Dialysis unit BP recordings were averaged over 2 weeks and home BP over 1 week. Awake ambulatory BP of > or =135 mmHg systolic or > or =85 mmHg diastolic was taken as evidence of hypertension. Average awake ambulatory BP was 128.1+/-21.6/73.5+/-13.5 mmHg, home BP 141.3+/-21.9/78.7+/-11.9 mmHg, standardized pre-dialysis BP 141.7+/-22.6/74.2+/-13.5 mmHg and post-dialysis 119.9+/-20.5/69.1+/-13.1 mmHg, routine pre-dialysis 145.4+/-21.8/79.0+/-13.1 mmHg and post-dialysis 131.5+/-19.2/72.5+/-11.4 mmHg. Sixty-three percent of the patients had well-controlled BP by ambulatory BP monitoring and isolated diastolic hypertension was rare (3%). The standard deviation of the differences between ambulatory and routine pre-dialysis BP was 17.6 mmHg, routine post-dialysis was 16.1 mmHg, standardized pre-dialysis was 16.4 mmHg, standardized post-dialysis was 14.1 mmHg, and home BP was 14.2 mmHg. The area under receiver operating characteristic curves was similar for home and standardized BP but lower for routine BP. Home systolic BP of > or =150 mmHg averaged over 1 week had the best combination of sensitivity (80%) and specificity (84.1%) in diagnosing systolic hypertension--present in 94% of the hypertensive dialysis patients. Home BP monitoring is similar to standardized recording of BP in hemodialysis patients. A systolic BP threshold of 150 mmHg at home averaged over 1 week serves as a useful predictor of hypertension diagnosed by ambulatory BP monitoring.

Blood pressure (BP) measured only in the clinic substantially misclassifies hypertension in patients with chronic kidney disease (CKD). The role of out-of-clinic recordings of BP in predicting end-stage renal disease (ESRD) and death in patients with CKD is unknown. A prospective cohort study was conducted in 217 Veterans with CKD. BP was measured at home and in the clinic by 'routine' and standardized methods. Patients were followed over a median of 3.5 years to assess the end points of total mortality, ESRD or the composite outcome of ESRD or death. Home BP was 147.0+/-21.4/78.3+/-11.6 mmHg and clinic BPs were 155.2+/-25.6/84.7+/-14.2 mmHg by standardized method and 144.5+/-24.2/75.4+/-14.7 mmHg by the 'routine' method. The composite renal end point occurred in 75 patients (34.5%), death in 52 patients (24.0%), and ESRD in 36/178 patients (20.2%). One standard deviation (s.d.) increase in systolic BP increased the risk of renal end point by 1.27 (95% confidence interval (CI) 1.01-1.60) for routine clinic measurement, by 1.69 (95% CI 1.32-2.17) for standardized clinic measurement and by 1.84 (95% CI 1.46-2.32) for home BP recording. One s.d. increase in home systolic BP increased the risk of ESRD by 1.74 (95% CI 1.04-2.93) when adjusted for standardized clinic systolic BP, proteinuria, estimated glomerular filtration rate, and other risk factors. In patients with CKD, BPs obtained at home are a stronger predictor of ESRD or death compared to BPs obtained in the clinic. Systolic home BP is an independent predictor for ESRD.

Background: Blood pressure (BP) measured outside the clinic correlates better with cardiovascular outcomes in patients with essential hypertension. To assess the role of out-of-clinic BP recordings in predicting cardiovascular events in patients with chronic kidney disease (CKD), a prospective cohort study was conducted in 217 veterans with CKD., Methods: BP was measured outside the clinic at home and by 24-hour ambulatory recordings, and in the clinic by 'routine' and standardized methods. Patients were followed over a median of 3.4 years to assess the combined end-point of total mortality, myocardial infarction or stroke., Results: Average (+/-SD) home BP was 147.0 +/- 21.4/78.3 +/- 11.6 mm Hg, 24-hour ambulatory BP 133.5 +/- 16.6/73.1 +/- 11.1 mm Hg and in-clinic BPs were 155.2 +/- 25.6/84.7 +/- 14.2 mm Hg by the standardized method, and 144.5 +/- 24.2/75.4 +/- 14.7 mm Hg by the 'routine' method. A 1 SD increase in systolic BP increased the hazard ratio (HR) of the composite end-point by 1.16 (95% CI 0.89-1.50) for routine BP, 1.57 (95% CI 1.19-2.09) for standardized BP, 1.66 (95% CI 1.27-2.17) for home BP, and 1.42 (95% CI 1.10-1.84) for 24-hour ambulatory BP recording. The HR of the composite end-point was only significant for hypertension defined by 24-hour ambulatory BP monitoring (HR 2.22 (95% CI 1.23-4.01)). Adjusted for the propensity scores, BP measured by the ambulatory technique was not an independent predictor of cardiovascular events. Non-dipping was associated with increased cardiovascular risk, but not when adjusted for other risk factors., Conclusion: Risk factors that differentiate hypertension or non-dipping appear to confer a cardiovascular risk in CKD., (Copyright (c) 2006 S. Karger AG, Basel.)

Blood pressures (BPs) obtained in the dialysis unit correlate poorly with ambulatory BP and left-ventricular hypertrophy (LVH). We compared the performance of BP obtained within and outside the dialysis unit as a correlate of LVH. BP was obtained in the dialysis unit using routine and standardized methods and outside the dialysis unit using home and ambulatory BP monitoring in 140 patients (mean age, 56 years; 89 men; 129 blacks; and 59 with diabetes mellitus) on chronic hemodialysis for > or =3 months. Dialysis unit BP recordings were averaged over 2 weeks, and home BP averaged over 1 week. Ambulatory BP monitoring was performed during an interdialytic interval. Echocardiography was performed immediately after dialysis for the assessment of left-ventricular mass. Left ventricular mass/height(2.7) of >51 g/m2 was taken as evidence of LVH. Test performance of various BPs was compared using receiver operating characteristic curves. Average ambulatory BP was 129.7+/-21.2/73.6+/-13.1 mm Hg, home BP was 139.4+/-21.2/79.0+/-12.5 mm Hg, standardized predialysis BP was 142.1+/-21.7/74.9+/-13.3 mm Hg, postdialysis was 120.9+/-20.8/69.6+/-12.5 mm Hg, routine predialysis was 145.6+/-20.7/79.4+/-13.1 mm Hg, and postdialysis was 132.0+/-19.3/72.6+/-11.1 mm Hg. Left ventricular mass/height(2.7) was 59.1+/-16.5, and 68% had LV hypertrophy. Diastolic BP measured by any technique was not associated with LVH. Routine and standardized measurements of BP were similarly weak correlates of LVH. Systolic BP outside the dialysis unit was a stronger correlate of LVH compared with dialysis unit BP.

Hypertension in patients with chronic kidney disease (CKD) is predominantly systolic. The contribution of risk factors for hypertension to the overall systolic blood pressure (BP) is unknown. To study the relationship between risk factors for hypertension and systolic BP in patients with CKD, 232 veterans (mean age 67 years; 96% men; 20% black; 39% with diabetes mellitus; estimated glomerular filtration rate [GFR] 48 mL/min per 1.73 m2) had clinic (routine and standardized measurements) and out-of-clinic (home and 24-hour ambulatory) BPs recorded. In multivariate analysis, using 17 risk factors, the log of the urine protein/creatinine ratio was the strongest predictor of systolic BP regardless of the BP measurement technique. The strength of the relationship between proteinuria and systolic BP was in the order ambulatory > home > standardized clinic > routine clinic BP measurement. Other independent predictors were age, race, and number of antihypertensive drugs used, and the model fit was better for out-of-clinic than clinic BP recordings. Estimated GFR was not an independent predictor of systolic BP by any technique. Nocturnal dipping was associated with higher estimated GFR, higher serum albumin, younger age, and less proteinuria. Proteinuria is the most important correlate of systolic BP in older men, the strongest relationship of which was with ambulatory and home systolic BP. Out-of-clinic BP recordings correlate better with target organ damage, as measured by proteinuria, and may be of greater clinical value than clinic BP recordings in predicting hypertension-related outcomes such as end-stage renal disease and death.

Background: Blood pressure (BP) control is the mainstay of stalling the progression of cardiorenal disease, yet the performance characteristics of BPs obtained in the clinic (CBPs) by routine or standardized methods or at home (HBP) in diagnosing hypertension or assessing its control are unknown., Methods: Two hundred thirty-two patients (20% black; 4% women; mean age, 67 years; 35% with diabetes) with chronic kidney disease (CKD) underwent a single 24-hour ambulatory BP (ABP) monitoring (ABPM) and concomitant recording of CBP and HBP for 1 week. Hypertension is defined as systolic BP of 130 mm Hg or greater or diastolic BP of 80 mm Hg or greater on average awake 24-hour ABPM., Results: Average ABP was 135.2 +/- 15.9/75.6 +/- 11.0 mm Hg. Thirty-five percent of patients had isolated systolic hypertension; 3%, isolated diastolic hypertension; 27%, combined systolic and diastolic hypertension; and 35%, normotension or well-controlled BP. The prevalence of "white-coat effect" was estimated as 28% to 30% by means of CBPs and 24% by means of HBPs. Well-controlled BP in the clinic, but poorly controlled BP by means of ABPM, masked hypertension, was seen in 26% to 29% by means of CBPs, but only 13% with HBP monitoring., Conclusion: In patients with CKD, HBP is superior in reducing the misclassification of hypertension caused by the white-coat effect and masked hypertension commonly seen with CBPs. An average HBP of approximately 140/80 mm Hg appears to be the best correlate of hypertension defined by means of ABPM.

The kidneys are vital in the pathogenesis of hypertension and are also pathologically affected by the presence of hypertension. The prevalence of hypertension in chronic kidney disease (CKD) depends on age, the severity of renal failure, and proteinuria. The intricate and inextricable relationship between CKD and hypertension seems to cause cardiovascular disease that has assumed epidemic proportions. This article discusses the etiology and treatment of hypertension in CKD so that it can be better controlled.

Background: Previous research has indicated that there may be only a modest degree of agreement between different reporters of a child's behaviour (mental health). This raises the possibility that some descriptions of the child's behaviour may reflect the personal characteristics of the respondent. We examine two potential sources of bias that may influence reports of a child's behaviour/mental health. The first is the mental or emotional impairment of the respondent; the second concerns gender-related expectations of children., Methods: Mothers (and their children after the birth) were assessed at first clinic visit, 3-5 days after the birth, then 6 months, 5 years and 14 years after the birth. Some 70% of respondents giving birth remained in the study at the 14-year follow-up, leaving some 5277 cases for this analysis. At the 14-year follow-up, child behaviour (mental health) was assessed using the Child Behaviour Check List and the Youth Self Report. Maternal mental health was determined using the anxiety and depression subscales of the Delusions-Symptoms-States Inventory., Results: Mothers who were not emotionally impaired reported fewer child behaviour problems than did the children themselves. As the mother's current emotional impairment increased, so her reports of the child's behaviour problems increased, when compared with the child's own reports. Further, mothers attributed more internalising symptoms to female respondents, and more externalising symptoms to male respondents, than did the child respondents themselves., Conclusions: Mothers differ systematically from their children when they are reporting their child's behaviour (mental health). The more emotionally impaired the mother, the greater the degree to which she imputes the child to have behaviour problems. Further, female children are attributed to have more internalising behaviours and male children externalising behaviours.

The relationships between severity, chronicity, and timing of maternal depressive symptoms and child outcomes were examined in a cohort of 4,953 children. Mothers provided self-reports of depressive symptoms during pregnancy, immediately postpartum, and when the child was 6 months old and 5 years old. At the age 5 follow-up, mothers reported on children's behavior and children completed a receptive vocabulary test. Results suggest that both the severity and the chronicity of maternal depressive symptoms are related to more behavior problems and lower vocabulary scores in children. The interaction of severity and chronicity of maternal depressive symptoms was significantly related to higher levels of child behavior problems. Timing of maternal symptoms was not significantly related to child vocabulary scores, but more recent reports of maternal depressive symptoms were associated with higher rates of child behavior problems.

Objective: A number of studies have consistently found that a mother's mental health (particularly her level of depression) is a strong predictor of mental health problems experienced by her child(ren). However, the validity of this finding is in doubt because the majority of these studies have relied on maternal reports as indicators of children's behavior., Method: This prospective, longitudinal study examines data on the mental health of the mother from prior to the birth of her child to when the child reaches 14 years of age. Child behavior is measured at 14 years of age using reports from mother and child. Mother and child responses are compared to provide an indication of the possible magnitude of maternal observation bias in the reporting of child behavior problems., Results: Anxious and/or depressed mothers tend to report more cases of child behavior problems than do their mentally healthy counterparts or children themselves. Differences between mothers and youths in reporting behavior problems appear to be related to the mothers' mental health., Conclusions: Current maternal mental health impairment appears to have a substantial effect on the reporting of child behavior problems by the mother, thereby raising questions about the validity of reports of child behavior by persons who are currently emotionally distressed.

Background: Much has been written about postnatal depression as a clinical condition. There is some evidence to suggest that a substantial proportion of women who give birth experience a depression in the postnatal period. This paper reports the results of a longitudinal study of the mental health of a large sample of women who were in the early stages of pregnancy at entry to the study., Methods: Each participant was assessed for symptoms of depression at the first clinic visit (entry to the study), and reassessed at various intervals--at 3-5 days, at 6 months, and again at 5 years after the birth of the child--using the DSSI-D (Delusions-Symptoms-States Inventory)., Results: Retrospective recall questions indicate that shortly after the birth the majority of women experienced some depressed mood. Of those who experienced depressed mood, the data suggest that the symptoms were not severe, nor did these symptoms generally continue beyond a few weeks. The longitudinal data indicate that levels of depression in our sample are highest either at the first clinic visit or at the 5-year follow-up. Rates of depression at the 6-month follow-up are relatively low by comparison., Conclusion: While most mothers experience periods of depressed mood after the birth of their baby, these periods are generally of short duration and of lesser intensity than a major depression. Mothers appear to experience increasing levels of symptoms of depression as their child grows up. Many of the "cases" of depression experienced at the 5-year follow-up represent a recurrence of a previous experience of depression.