Determining the minimal clinically important difference for the PEmbQoL questionnaire, a measure of pulmonary embolism-specific quality of life.

Essentials The minimal clinically important difference (MCID) for PEmbQoL has not yet been determined. We estimated the MCID for PEmbQoL and its subscales via anchor- and distribution-based approaches. Our results indicate that MCID for PEmbQoL appears to be 15 points. Our work enables interpretation of changes or differences in PEmbQoL. SUMMARY: Background Pulmonary embolism (PE) reduces quality of life (QOL). The PEmbQoL questionnaire, a PE-related QOL measure, was recently developed and validated and has been used to quantify disease-specific QOL in clinical studies of patients with PE. However, to date, interpretation of PEmbQoL scores has been limited by a lack of information on the minimal clinically important difference (MCID) of this measure. Objective To determine the MCID for PEmbQoL and its subscales using anchor-based and distribution-based approaches. Methods We analyzed data from the ELOPE Study, a prospective, multicenter cohort study of long-term outcomes after a first episode of acute PE. At baseline and 1, 3, 6 and 12 months after PE, we measured generic QOL (SF-36), PE-specific QOL (PEmbQoL) and dyspnea severity (UCSD Shortness of Breath Questionnaire). We used time-varying repeated-measures mixed-effect models to estimate anchor-based MCID and effect sizes to estimate distribution-based MCID. Results Eighty-two patients participated in this sub-study. Their mean age was 49.4 years, 60% were male and 84% had PE diagnosed in an outpatient setting. Using both anchor- and distribution-based approaches, the MCID for PEmbQoL appears to be 15 points. Based on this MCID, 42%, 59%, 66% and 75% of patients experienced at least one MCID unit of improvement in PEmbQoL from baseline to 1, 3, 6 and 12 months, respectively. Conclusion Our results provide new information on the MCID of PEmbQoL, a PE-specific QOL questionnaire that can be used by researchers and clinicians to measure and interpret changes in PE-specific QOL over time, or as an outcome in clinical trials.

Impact of Left Ventricular Diastolic Dysfunction on Lung Transplantation Outcome in Patients With Pulmonary Arterial Hypertension.

Diastolic dysfunction may influence perioperative outcome, early graft function, and long-term survival. We compared the outcomes of double lung transplantation (DLTx) for patients with pulmonary arterial hypertension (PAH) with preoperative left ventricular (LV) diastolic dysfunction with the outcomes of patients without diastolic dysfunction. Of 116 consecutive patients with PAH (who underwent transplantation between January 1995 and December 2013), 44 met our inclusion and exclusion criteria. Fourteen (31.8%) patients with diastolic dysfunction pretransplantation had a higher body mass index (29 [IQR 21.5-32.6] vs 22.4 [IQR 19.9-25.3] kg/m2 ) and mean pulmonary arterial pressure (54.6 ± 10 mmHg vs 47 ± 11.3 mmHg) and right atrial pressure (16.5 ± 5.2 mmHg vs 10.6 ± 5.2 mmHg). The patients received extracorporeal life support more frequently (33% vs 7% [p = 0.02]), had worse APACHE II scores (21.7 ± 7.4 vs 15.3 ± 5.3 [p = 0.02]), and a trend toward worse ventilator-free days (2.5 [IQR 6.5-32.5] vs 17 [IQR 3-23] [p = 0.08]). There was no effect on development of primary graft dysfunction or intensive care unit/hospital survival. One-year survival was worse (hazard ratio [HR] 4.45, 95% confidence interval [CI] 1.3-22, p = 0.02). Diastolic dysfunction was the only variable that correlated with overall survival (HR 5.4, 95% CI 1.3-22, p = 0.02). Diastolic dysfunction leads to early postoperative morbidity and worse survival in patients with PAH after DLTx.

Proposed management algorithm for severe hypoxemia after liver transplantation in the hepatopulmonary syndrome.

The hepatopulmonary syndrome (HPS) is defined as the triad of liver disease, intrapulmonary vascular dilatation, and abnormal gas exchange, and is found in 10-32% of patients with liver disease. Liver transplantation is the only known cure for HPS, but patients can develop severe posttransplant hypoxemia, defined as a need for 100% inspired oxygen to maintain a saturation of ≥85%. This complication is seen in 6-21% of patients and carries a 45% mortality. Its management requires the application of specific strategies targeting the underlying physiologic abnormalities in HPS, but awareness of these strategies and knowledge on their optimal use is limited. We reviewed existing literature to identify strategies that can be used for this complication, and developed a clinical management algorithm based on best evidence and expert opinion. Evidence was limited to case reports and case series, and we determined which treatments to include in the algorithm and their recommended sequence based on their relative likelihood of success, invasiveness, and risk. Recommended therapies include: Trendelenburg positioning, inhaled epoprostenol or nitric oxide, methylene blue, embolization of abnormal pulmonary vessels, and extracorporeal life support. Availability and use of this pragmatic algorithm may improve management of this complication, and will benefit from prospective validation.

Pulmonary hypertension in systemic sclerosis and systemic lupus erythematosus.

Pulmonary arterial hypertension (PAH) is a severe manifestation of systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). Due to improvements in the understanding of the pathogenesis of these diseases, improved methodological rigour in the conduct of epidemiological studies and the advent of successful therapies, our understanding of SSc-PAH and SLE-PAH has evolved considerably. In this review we will review the current evidence regarding the prevalence, prognostic factors and survival estimates for SSc-PAH and SLE-PAH. In doing so, we will compare and contrast these two diseases, highlight clinically useful features, discuss methodological limitations of existing data, and draw attention to areas where research is needed.

Patent foramen ovale does not have a negative impact on early outcomes in patients undergoing liver transplantation.

OBJECTIVE: To identify the impact of the presence of patent foramen ovale (PFO) in patients undergoing liver transplantation. METHODS: Twenty-seven pre-liver transplant patients who had a PFO (PFO group) were identified and compared with 61 patients without PFO (NoPFO group). Patients were matched according to age, gender and cause of liver disease. The diagnosis of PFO was made by transthoracic echocardiography prior to liver transplantation. Patient baseline characteristics and complications during the early post-transplant period were analyzed. RESULTS: The mean age in the PFO group was 47 ± 14 (range 18-68) yr and 50 ± 11 (range 12-65) yr in the NoPFO group. The PFO group had a mean model for end-stage liver disease (MELD) score of 15 ± 10 whereas in the NoPFO group the MELD score was 19 ± 10 (p = 0.08). There were non-significant differences in echocardiographic parameters between groups. Duration of mechanical ventilation and the incidence of neurological complications were similar. Thirty-day mortality rate was similar in both groups; only one patient in the NoPFO group died within the first 30 days post-transplantation. CONCLUSIONS: The presence of PFO in patients with end-stage liver disease undergoing liver transplantation does not appear to affect patient outcomes during the peri-operative period.

The pulmonary vascular complications of hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder, characterised by the presence of vascular malformations. The pulmonary vascular complications of HHT include pulmonary arteriovenous malformations, pulmonary hypertension associated with high-output heart failure and liver vascular malformations and, finally, pulmonary arterial hypertension secondary to HHT. In the present review, the authors describe the clinical presentation, diagnosis and management of all three pulmonary vascular presentations of HHT, as well as the underlying genetics and pathophysiology.

Discordance between microneurographic and heart-rate spectral indices of sympathetic activity in pulmonary arterial hypertension.

OBJECTIVES: To determine, in patients with pulmonary arterial hypertension (PAH), whether there is a relationship: (1) between sympathetic nerve firing rate and spectral indices of sympathetic neural heart rate modulation; and (2) between heart rate variability (HRV) and right atrial pressure, a stimulus to sinoatrial node stretch. DESIGN: Characterisation of patients and healthy controls. SETTING: Teaching hospital-based study. PATIENTS: 9 PAH patients without elevated pulmonary capillary wedge pressure and nine age-matched control subjects. INTERVENTIONS: Heart rate (HR) and muscle sympathetic nerve activity (MSNA) were recorded during 10 min of supine rest in both PAH patients studied after right heart catheterisation, and healthy volunteers. Coarse-graining spectral analysis determined HR spectral power. MAIN OUTCOME MEASURES: (1) Low-frequency (PL) spectral component of HRV; (2) MSNA burst frequency; and in PAH patients: (3) right atrial pressure. RESULTS: MSNA burst frequency was higher in PAH patients (48 (24) and 29 (11) bursts/min, respectively; mean (SD); p = 0.05), whereas total power (p = 0.01), its fractal (p<0.01) and harmonic (p = 0.04) components, and PL (p = 0.01) were all reduced. PL related inversely to both MSNA burst frequency (r = -0.86, p = 0.005) and right atrial systolic pressure (r = -0.77, p = 0.04). CONCLUSIONS: Thus, in PAH (as in patients with left ventricular systolic dysfunction) loss of PL relates inversely to gain in MSNA burst frequency. Diminished sympathetic neural heart rate modulation and increased right atrial stretch may combine to attenuate HRV, an adverse prognostic marker.

Outcomes in patients with pulmonary hypertension undergoing percutaneous atrial septal defect closure.

OBJECTIVES: To examine the outcomes in patients with moderate or severe pulmonary arterial hypertension (PAH) undergoing percutaneous atrial septal defect (ASD) closure. DESIGN: Retrospective study. SETTING: Teaching hospital-based study. PATIENTS: Fifty-four patients with moderate (n = 34) or severe PAH (n = 20) who underwent successful device implantation between 1999 and 2004 were included in the study. Clinical and transthoracic echocardiographic data were reviewed. Pulmonary hypertension was classified as moderate (50-59 mm Hg) or severe (>or=60 mm Hg) according with the right ventricular systolic pressure (RVSP) calculated by echocardiography. RESULTS: At the early follow-up (mean (SD) 2.3 (1.2) months) all patients were alive and the baseline RVSP decreased from 57 (11) mm Hg to 51 (17) mm Hg (p = 0.003). At the late follow-up (n = 39, mean (SD) duration 31 (15) months) two patients had died and the baseline RVSP decreased from 58 (10) mm Hg to 44 (16) mm Hg (p = 0.004). Although the overall mean RVSP decreased at late follow-up, only 43.6% (17/39) of patients had normalisation (<40 mm Hg) of the RVSP and 15.4% (6/39) had persistent severe PAH. CONCLUSION: Transcatheter closure in patients with secundum ASD and PAH can be successfully performed in selected subjects and is associated with good outcomes. Early improvements in RVSP are seen in patients with moderate or severe PAH undergoing transcatheter ASD closure. Continued improvement in RVSP occurs in late follow-up. Despite decreases in the mean RVSP in late follow-up, many patients do not have complete normalisation of pressures.

Anticoagulation in pulmonary arterial hypertension: a qualitative systematic review.

Thrombotic arteriopathy has been implicated in the pathophysiology of pulmonary arterial hypertension (PAH). However, the role of anticoagulants in the treatment of PAH is uncertain. Through a qualitative systematic review of epidemiological studies, the effectiveness of anticoagulation therapy with warfarin on survival was evaluated in patients with PAH. MEDLINE (1966 to November 2005), EMBASE (1966 to November 2005), bibliographies of included studies and published reviews were searched without language restriction. Epidemiological studies evaluating the effectiveness of warfarin in PAH were included. Studies had to report mortality as an outcome. Seven observational studies evaluating the effectiveness of warfarin comprising 488 patients were identified. Five studies support the effectiveness of anticoagulation therapy, whereas two do not. Data from observational studies suggest that anticoagulation therapy may be an effective intervention in pulmonary arterial hypertension. However, given the methodological limitations and the small number of existing observational studies, a randomised controlled trial is needed in order to definitively address this important clinical issue.

Pulmonary hypertension in systemic lupus.

Pulmonary arterial hypertension (PAH) has devastating consequences in the rheumatic diseases; however, the prevalence in lupus is not well delineated. We searched the University of Toronto lupus database to ascertain the first echocardiogram ordered at their physician's discretion between 1995 and 2002. We reviewed the echocardiogram reports for right ventricular systolic pressure (RVSP), valvular disease, and atrial and ventricular function. The PAH was defined as RVSP > or = 40 mmHg. Patients were divided into three groups: RVSP > or = 40 mmHg, RVSP = 30-39 mmHg and RVSP < 30 mmHg. We analysed potential associations between presence of PAH and lupus including disease activity, organ involvement and anticardiolipin antibodies, both at the time of and any time prior to echocardiography. In total, 129 patients underwent echocardiography. Nine patients' echocardiograms were not obtainable, and three patients were excluded from analysis, as their visit was more than six months from the date of echocardiography. Sixteen patients (14%) had RVSP > or = 40 mmHg, 43 (37%) patients had RVSP of 30-39, and 60 (51%) patients had RVSP < 30 mmHg. There was no statistical difference in disease activity, organ involvement or serology among all three groups. In conclusion, the prevalence of PAH (RVSP > or = 40 mmHg) on first echocardiogram ordered at physician discretion in our cohort was 14%. An RVSP of 30-39 mmHg was found in 37% of patients. Although abnormal, the clinical significance of this finding is unknown. Disease activity, organ involvement and anticardiolipin antibodies were not associated with PAH. Further research is needed to identify the mechanism, response to immunosuppression and impact on quality of life in these patients.

Lung function and aerobic capacity in adult patients following modified Fontan procedure.

OBJECTIVE: To examine cardiopulmonary performance in 52 adult patients with a Fontan circulation. DESIGN: Retrospective cohort study. Values of maximum oxygen uptake (VO(2)max), maximum heart rate (HRmax), forced vital capacity (FVC), and forced expiratory volume in one second (FEV(1)) were compared with predictive values for different age groups. Patients were further subdivided into those with a pulmonary artery connection (RA-PA) or right atrium to right ventricle conduit (RA-RV). RESULTS: At late follow up (median 10 years, range 1 to 26 years), patients with Fontan circulation had greatly diminished VO(2)max, HRmax, FVC, and FEV(1) compared with predicted values. Early age at surgery had a positive impact on aerobic capacity. The FEV(1):FVC ratio indicated restrictive lung function. No differences were found with respect to any variable between patients with RA-PA connections and those with RA-RV connections. CONCLUSIONS: Patients with a Fontan circulation have greatly diminished values of aerobic capacity and a restrictive pattern of lung function. Patients with an early surgical procedure obtained higher values of VO(2)max. The theoretical benefits of including the right ventricle in a Fontan circulation were not apparent.

Use of a screen log to audit patient recruitment into multiple randomized trials in the intensive care unit. Canadian Critical Care Trials Group.

OBJECTIVE: To develop and evaluate a screen log for monitoring enrollment in multiple randomized clinical trials conducted in a single center. SETTING: University-affiliated 20-bed tertiary care medical-surgical intensive care unit (ICU). PATIENTS: Consecutive ICU patients admitted between April 1995 and March 1997. METHODS: We developed a screen log for multicentered studies conducted in our ICU. Using a multiple-project, unicenter perspective, we evaluated the screen log as a tool for monitoring eligibility and enrollment of patients in four multicentered randomized trials focused on stress ulcer prophylaxis, blood transfusion thresholds, immunotherapy for sepsis and mechanical ventilation strategies. RESULTS: The screen log was used as an instrument to monitor trial execution. We recorded all aspects of study enrollment and created a taxonomy of reasons for nonenrollment into each trial. We calculated enrollment efficiency rates and used these data to develop strategies to maximize accrual. The screen log became a communication tool that fostered research-oriented continuous quality improvement initiatives for the management of concurrently conducted randomized trials in our ICU. CONCLUSIONS: Intensivists participating in several clinical trials may be interested in monitoring and maximizing enrollment when conducting multiple studies and understanding the influence of each trial on enrollment into the others. The unicenter, multiple-project screen log is one tool that may help to achieve these goals.

Interobserver variability in applying a radiographic definition for ARDS.

CONTEXT: Acute lung injury (ALI) and ARDS are currently defined by the American-European Consensus Conference (AECC) definition criteria, which contain a radiographic criterion. The accuracy or reliability of this consensus radiographic definition has not been evaluated, and no radiographic definition of ALI-ARDS has been evaluated by a large international group of experts. OBJECTIVE: To study the interobserver variability in applying the AECC radiographic criterion for ALI-ARDS. DESIGN: Survey. PARTICIPANTS: A convenience sample of 21 experts selected from participants attending the 1997 Toronto Mechanical Ventilation Workshop and from members of the National Institutes of Health ARDS Network. OUTCOME MEASURES: Participants reviewed 28 randomly selected chest radiograph from critically ill, hypoxemic (PaO(2)/fraction of inspired oxygen ratio, < 300) patients and decided whether the radiograph fulfilled the AECC definition for ALI-ARDS. RESULTS: Interobserver agreement in applying the AECC definition for ALI-ARDS was moderate (kappa = 0.55; 95% confidence interval, 0.52 to 0.57). Thirteen radiographs (43%) showed nearly complete agreement (defined as 20 or 21 readers in agreement). Nine radiographs (32%) had more than or equal to five dissenting readers. The percentage of radiographs interpreted as consistent with ALI-ARDS by individual readers ranged from 36 to 71%. Participants commented that mild infiltrates, pleural effusions, atelectasis, isolated lower lobe involvement, radiographic technique, and overlying monitoring equipment posed the most difficulties. CONCLUSIONS: The radiographic criterion used in the current AECC definition for ALI-ARDS showed high interobserver variability when applied by expert investigators in the fields of mechanical ventilation and ARDS. This variability may result in differences in ALI-ARDS populations at different clinical research centers and may make it difficult for clinicians to apply the results of clinical trials to their patients. Modifications to the radiographic criterion or annotated reference radiograph may improve the reliability of future definitions for ALI-ARDS.

Expression of the cell adhesion molecules on leukocytes that demarginate during acute maximal exercise.

The pulmonary vascular bed is an important reservoir for the marginated pool of leukocytes that can be mobilized by exercise or catecholamines. This study was designed to determine the phenotypic characteristics of leukocytes that are mobilized into the circulation during exercise. Twenty healthy volunteers performed incremental exercise to exhaustion [maximal O2 consumption (VO2 max)] on a cycle ergometer. Blood was collected at baseline, at 3-min intervals during exercise, at VO2 max, and 30 min after exercise. Total white cell, polymorphonuclear leukocyte (PMN), and lymphocyte counts increased with exercise to VO2 max (P < 0.05). Flow cytometric analysis showed that the mean fluorescence intensity of L-selectin on PMN (from 14.9 +/- 1 at baseline to 9.5 +/- 1.6 at VO2 max, P < 0.05) and lymphocytes (from 11.7 +/- 1.2 at baseline to 8 +/- 0.8 at VO2 max, P < 0.05) decreased with exercise. Mean fluorescence intensity of CD11b on PMN increased with exercise (from 10.2 +/- 0.6 at baseline to 25 +/- 2.5 at VO2 max, P < 0.002) but remained unchanged on lymphocytes. Myeloperoxidase levels in PMN did not change with exercise. In vitro studies showed that neither catecholamines nor plasma collected at VO2 max during exercise changed leukocyte L-selectin or CD11b levels. We conclude that PMN released from the marginated pool during exercise express low levels of L-selectin and high levels of CD11b.