Chronic thromboembolic disease is characterised by persistent pulmonary thromboembolic occlusions without pulmonary hypertension. Early surgical treatment with pulmonary endarterectomy may improve ...symptoms and prevent disease progression. We sought to assess the outcome of pulmonary endarterectomy in symptomatic patients with chronic thromboembolic disease. Patients with symptomatic chronic thromboembolic disease and a mean pulmonary artery pressure <25 mmHg at baseline with right heart catheterisation and treated with pulmonary endarterectomy between January 2000 and July 2013 were identified. Patients were reassessed at 6 months and at 1 year following surgery. A total of 42 patients underwent surgery and the median length of stay in hospital was 11 days. There was no in-hospital mortality but complications occurred in 40% of patients. At 1 year, following surgery, 95% of the patients remained alive. There was a significant symptomatic improvement with 95% of patients in the New York Heart Association functional classes I or II at 6 months. There was a significant improvement in quality of life assessed by the Cambridge pulmonary hypertension outcome review questionnaire. In this carefully selected cohort of chronic thromboembolic disease patients, pulmonary endarterectomy resulted in significant improvement in symptoms and quality of life. Appropriate patient selection is paramount given the known surgical morbidity and mortality, and surgery should only be performed in expert centres.
Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon complication of acute pulmonary emboli necessitating lifelong anticoagulation. Despite this, few data exist on the safety and ...efficacy of vitamin K antagonists (VKAs) in CTEPH and none for direct oral anticoagulants (DOACs).
To evaluate outcomes and complication rates in CTEPH following pulmonary endarterectomy (PEA) for individuals receiving VKAs or DOACs.
Consecutive CTEPH patients undergoing PEA between 2007 and 2018 were included in a retrospective analysis. Postoperative outcomes, recurrent venous thromboembolism (VTE), and bleeding events were obtained from patient medical records.
Seven hundred ninety-four individuals were treated with VKAs and 206 with DOACs following PEA. Mean observation period was 612 (standard deviation: 702) days. Significant improvements in hemodynamics and functional status were observed in both groups following PEA (P < .001). Major bleeding events were equivalent (P = 1) in those treated with VKAs (0.67%/person-year) and DOACs (0.68%/person-year). The VTE recurrence was proportionately higher (P = .008) with DOACs (4.62%/person-year) than VKAs (0.76%/person-year), although survival did not differ.
Post-PEA functional and hemodynamic outcomes appear unaffected by anticoagulant choice. Bleeding events were similar, but recurrent VTE rates significantly higher in those receiving DOACs. Our study provides a strong rationale for prospective registry data and/or studies to evaluate the safety of DOACs in CTEPH.
Chronic thromboembolic pulmonary hypertension results from incomplete resolution of pulmonary emboli. Pulmonary endarterectomy (PEA) is potentially curative, but residual pulmonary hypertension ...following surgery is common and its impact on long-term outcome is poorly understood. We wanted to identify factors correlated with poor long-term outcome after surgery and specifically define clinically relevant residual pulmonary hypertension post-PEA.
Eight hundred eighty consecutive patients (mean age, 57 years) underwent PEA for chronic thromboembolic pulmonary hypertension. Patients routinely underwent detailed reassessment with right heart catheterization and noninvasive testing at 3 to 6 months and annually thereafter with discharge if they were clinically stable at 3 to 5 years and did not require pulmonary vasodilator therapy. Cox regressions were used for survival (time-to-event) analyses. Overall survival was 86%, 84%, 79%, and 72% at 1, 3, 5, and 10 years for the whole cohort and 91% and 90% at 1 and 3 years for the recent half of the cohort. The majority of patient deaths after the perioperative period were not attributable to right ventricular failure (chronic thromboembolic pulmonary hypertension). At reassessment, a mean pulmonary artery pressure of ≥30 mm Hg correlated with the initiation of pulmonary vasodilator therapy post-PEA. A mean pulmonary artery pressure of ≥38 mm Hg and pulmonary vascular resistance ≥425 dynes·s(-1)·cm(-5) at reassessment correlated with worse long-term survival.
Our data confirm excellent long-term survival and maintenance of good functional status post-PEA. Hemodynamic assessment 3 to 6 months and 12 months post-PEA allows stratification of patients at higher risk of dying of chronic thromboembolic pulmonary hypertension and identifies a level of residual pulmonary hypertension that may guide the long-term management of patients postsurgery.
People who begin daily smoking at an early age are at greater risk of long-term nicotine addiction. We tested the hypothesis that associations between nicotinic acetylcholine receptor (nAChR) genetic ...variants and nicotine dependence assessed in adulthood will be stronger among smokers who began daily nicotine exposure during adolescence. We compared nicotine addiction-measured by the Fagerstrom Test of Nicotine Dependence-in three cohorts of long-term smokers recruited in Utah, Wisconsin, and by the NHLBI Lung Health Study, using a candidate-gene approach with the neuronal nAChR subunit genes. This SNP panel included common coding variants and haplotypes detected in eight alpha and three beta nAChR subunit genes found in European American populations. In the 2,827 long-term smokers examined, common susceptibility and protective haplotypes at the CHRNA5-A3-B4 locus were associated with nicotine dependence severity (p = 2.0x10(-5); odds ratio = 1.82; 95% confidence interval 1.39-2.39) in subjects who began daily smoking at or before the age of 16, an exposure period that results in a more severe form of adult nicotine dependence. A substantial shift in susceptibility versus protective diplotype frequency (AA versus BC = 17%, AA versus CC = 27%) was observed in the group that began smoking by age 16. This genetic effect was not observed in subjects who began daily nicotine use after the age of 16. These results establish a strong mechanistic link among early nicotine exposure, common CHRNA5-A3-B4 haplotypes, and adult nicotine addiction in three independent populations of European origins. The identification of an age-dependent susceptibility haplotype reinforces the importance of preventing early exposure to tobacco through public health policies.
ObjectiveInoperable chronic thromboembolic pulmonary hypertension (CTEPH) managed medically has a poor prognosis. Balloon pulmonary angioplasty (BPA) offers a new treatment for inoperable patients. ...The national BPA service for the UK opened in October 2015 and we now describe the treatment of our initial patient cohort.MethodsThirty consecutive, inoperable, anatomically suitable, symptomatic patients on stable medical therapy for CTEPH were identified and offered BPA. They initially underwent baseline investigations including Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) quality of life (QoL) questionnaire, cardiopulmonary exercise test, 6 min walk distance (6MWD), transthoracic echocardiography, N-terminal probrain natriuretic peptide (NT pro-BNP) and right heart catheterisation. Serial BPA sessions were then performed and after completion, the treatment effect was gauged by comparing the same investigations at 3 months follow-up.ResultsA median of 3 (IQR 1–6) BPA sessions per patient resulted in a significant improvement in functional status (WHO functional class ≥3: 24 vs 4, p<0.0001) and QoL (CAMPHOR symptom score: 8.7±5.4 vs 5.6±6.1, p=0.0005) with reductions in pulmonary pressures (mean pulmonary artery pressure: 44.7±11.0 vs 34.4±8.3 mm Hg, p<0.0001) and resistance (pulmonary vascular resistance: 663±281 vs 436±196 dyn.s.cm-5, p<0.0001). Exercise capacity improved (minute ventilation/carbon dioxide production: 55.3±12.2 vs 45.0±7.8, p=0.03 and 6MWD: 366±107 vs 440±94 m, p<0.0001) and there was reduction in right ventricular (RV) stretch (NT pro-BNP: 442 (IQR 168–1607) vs 202 (IQR 105–447) pg/mL, p<0.0001) and dimensions (mid RV diameter: 4.4±1.0 vs 3.8±0.7 cm, p=0.002). There were no deaths or life-threatening complications and the mild-moderate per-procedure complication rate was 10.5%.ConclusionsBPA is safe and improves the functional status, QoL, pulmonary haemodynamics and RV dimensions of patients with inoperable CTEPH.
The influence of teammates' shared mental models on team processes and performance was tested using 56 undergraduate dyads who "flew" a series of missions on a personal-computer-based flight-combat ...simulation. The authors both conceptually and empirically distinguished between teammates' task- and team-based mental models and indexed their convergence or "sharedness" using individually completed paired-comparisons matrices analyzed using a network-based algorithm. The results illustrated that both shared-team- and task-based mental models related positively to subsequent team process and performance. Furthermore, team processes fully mediated the relationship between mental model convergence and team effectiveness. Results are discussed in terms of the role of shared cognitions in team effectiveness and the applicability of different interventions designed to achieve such convergence.
Acute lung injury (ALI) is a common but poorly defined and understood complication of balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). Little data are ...available on the medium term clinical outcomes of BPA complicated by ALI. We analyzed per‐procedure data from 282 procedures in 109 patients and per‐patient data from 85 patients. Serial right heart catheterization at baseline, after each BPA and at 3‐month follow‐up measured pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP), and cardiac output (CO). ALI (ALI+) was identified by chest radiography alone (ALIr+) or in association with hypoxia clinically (ALIcr+). Procedural predictors of ALI and patient outcomes at 3‐months were compared no ALI (ALI−). ALI+ occurred in 17/282 (6.0%) procedures (ALIcr+: 2.5%, ALIr+: 3.5%). Prevailing haemodynamics (PVR: p < 0.01; mPAP: p < 0.05) at a procedural and patient level, as well as number of BPA sessions (p < 0.01), total number of vessels (p < 0.05), and occlusions (p < 0.05) treated at a patient level predicted ALI+. Those with ALI had greater percentage improvement in ΔCAMPHOR symptoms score (ALI+: −63.5 ± 35.7% (p < 0.05); ALIcr+: −84.4 ± 14.5% (p < 0.01); ALI−: −27.2 ± 74.2%) and ΔNT‐proBNP (ALIcr+: −78.4 ± 11.9% (p < 0.01); ALI−: −42.9 ± 36.0%) at follow‐up. There was no net significant difference in haemodynamic changes in ALI+ versus ALI− at follow‐up. ALI is predicted by haemodynamic severity, number of vessels treated, number of BPA sessions, and treating occlusive disease. ALI in this cohort was associated with a clinical advantage at follow‐up.
We tested the impact of teammates' team and task mental model sharedness on team processes and performance using 70 undergraduate teams that completed a series of missions on a PC-based flight ...simulator. Moreover, we considered how the quality of mental models might moderate such relationships. Team processes were found to partially mediate the relationship between task mental model sharedness and team performance. Although team mental model sharedness failed to exhibit a significant linear relationship with team processes or performance, it did evidence a multiplicative relationship as moderated by the quality of those models. Team processes and performance were better among teams sharing higher-quality team mental models than among teams evidencing less sharedness or who had lower-quality models. Again, team processes partially mediated these relationships. Results are discussed in terms of the equifinality of mental model quality and applications to various team environments.
Abdominal obesity is associated with metabolic abnormalities and increased risk of atherosclerotic cardiovascular disease. However, no obesity management strategy has demonstrated the ability to slow ...progression of coronary disease.
To determine whether weight loss and metabolic effects of the selective cannabinoid type 1 receptor antagonist rimonabant reduces progression of coronary disease in patients with abdominal obesity and the metabolic syndrome.
Randomized, double-blinded, placebo-controlled, 2-group, parallel-group trial (enrollment December 2004-December 2005) comparing rimonabant with placebo in 839 patients at 112 centers in North America, Europe, and Australia.
Patients received dietary counseling, were randomized to receive rimonabant (20 mg daily) or matching placebo, and underwent coronary intravascular ultrasonography at baseline (n = 839) and study completion (n = 676).
The primary efficacy parameter was change in percent atheroma volume (PAV); the secondary efficacy parameter was change in normalized total atheroma volume (TAV).
In the rimonabant vs placebo groups, PAV (95% confidence interval CI) increased 0.25% (-0.04% to 0.54%) vs 0.51% (0.22% to 0.80%) (P = .22), respectively, and TAV decreased 2.2 mm3 (-4.09 to -0.24) vs an increase of 0.88 mm3 (-1.03 to 2.79) (P = .03). In the rimonabant vs placebo groups, imputing results based on baseline characteristics for patients not completing the trial, PAV increased 0.25% (-0.04% to 0.55%) vs 0.57% (0.29% to 0.84%) (P = .13), and TAV decreased 1.95 mm3 (-3.8 to -0.10) vs an increase of 1.19 mm3 (-0.73 to 3.12) (P = .02). Rimonabant-treated patients had a larger reduction in body weight (4.3 kg -5.1 to -3.5 vs 0.5 kg -1.3 to 0.3) and greater decrease in waist circumference (4.5 cm -5.4 to -3.7 vs 1.0 cm -1.9 to -0.2) (P < .001 for both comparisons). In the rimonabant vs placebo groups, high-density lipoprotein cholesterol levels increased 5.8 mg/dL (4.9 to 6.8) (22.4%) vs 1.8 mg/dL (0.9 to 2.7) (6.9%) (P < .001), and median triglyceride levels decreased 24.8 mg/dL (-35.4 to -17.3) (20.5%) vs 8.9 mg/dL (-14.2 to -1.8) (6.2%) (P < .001). Rimonabant-treated patients had greater decreases in high-sensitivity C-reactive protein (1.3 mg/dL -1.7 to -1.2 50.3% vs 0.9 mg/dL -1.4 to -0.5 30.9%) and less increase in glycated hemoglobin levels (0.11% 0.02% to 0.20% vs 0.40% 0.31% to 0.49%) (P < .001 for both comparisons). Psychiatric adverse effects were more common in the rimonabant group (43.4% vs 28.4%, P < .001).
After 18 months of treatment, the study failed to show an effect for rimonabant on disease progression for the primary end point (PAV) but showed a favorable effect on the secondary end point (TAV). Determining whether rimonabant is useful in management of coronary disease will require additional imaging and outcomes trials, which are currently under way.
clinicaltrials.gov Identifier: NCT00124332.
Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are ...disease free.
To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0.
Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration FEV1 to forced vital capacity >0.7 and FEV1 ≥80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n = 3690), and a group of never smokers (n = 108). Recruitment began in January 2008 and ended in July 2011.
Physical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life.
One or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean SD St George's Respiratory Questionnaire total score, 17.0 18.0 vs 3.8 6.8 for the never smokers; P < .001) and a lower 6-minute walk distance, and 42.3% (127 of 300) of the GOLD 0 group had CT evidence of emphysema or airway thickening. The FEV1 percent predicted distribution and mean for the GOLD 0 group were lower but still within the normal range for the population. Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping. Advancing age was associated with smoking cessation and with more CT findings of disease. Individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associated with worse disease.
Lung disease and impairments were common in smokers without spirometric COPD. Based on these results, we project that there are 35 million current and former smokers older than 55 years in the United States who may have unrecognized disease or impairment. The effect of chronic smoking on the lungs and the individual is substantially underestimated when using spirometry alone.
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