Agreement between Cardiopulmonary Exercise Test and Modified 6-Min Walk Test in Determining Oxygen Uptake in COPD Patients with Different Severity Stages.

BACKGROUND: In moderate-to-severe chronic obstructive pulmonary disease (COPD) patients the 6-min walk test (6MWT) is often exhaustive and correlates with the incremental cycle cardiopulmonary exercise test (CPET). OBJECTIVES: The aim of this study was to assess the agreement between oxygen uptake (VO2) measured during the 6MWT by portable equipment and incremental cycle exercise in COPD patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-IV. METHODS: A total of 30 patients with COPD GOLD I-IV (14 patients GOLD stage I and II and 16 patients GOLD stage III and IV) underwent a 6MWT and an incremental CPET. Breath-by-breath analysis for VO2, carbon dioxide output (VCO2), and minute ventilation (VE) were measured during each test. Blood gas analysis and lactate measurements were performed before, during, and after the test. RESULTS: VO2 in COPD patients GOLD stage I and II was 16.2 ± 4.2 mL/kg/min measured by 6MWT and 20.5 ± 7.0 mL/kg/min measured by CPET as compared to GOLD stage III and IV (11.2 ± 3.7 mL/kg/min measured by 6MWT and 15.5 ± 4.3 mL/kg/min measured by CPET). No significant correlation in VO2 measurements could be found between both tests in COPD GOLD I and II (r = 0.17), whereas the VO2 significantly correlated in patients with COPD stage III and IV (r = 0.7). CONCLUSIONS: A significant relationship between VO2 measured by 6MWT and CPET could only be found in patients with more severe COPD but not in milder stages. 6MWT and CPET provide different VO2 measurements in COPD patients. The two methods cannot be used interchangeably.

Diameter of the Pulmonary Artery in Relation to the Ascending Aorta: Association with Cardiovascular Outcome.

Purpose To investigate whether the pulmonary artery (PA)-to-ascending aorta (Ao) ratio is associated with outcome in unselected patients referred for cardiac magnetic resonance (MR) imaging. Materials and Methods This study prospectively enrolled 650 consecutive patients (47.2% women; mean age, 56.1 years ± 17.7 [standard deviation]). Diameters of PA and Ao were measured in axial black blood images. On the basis of previous results, a PA-to-Ao ratio of 1.0 or greater was chosen as the cutoff for further analysis. Univariable and multivariable Cox regression models were used to investigate the primary end point, which was defined as a composite of cardiovascular hospitalization and death. Results A PA-to-Ao ratio of 1.0 or greater was present in 131 (20.2%) patients. Patients with a PA-to-Ao ratio of 1.0 or greater were predominantly women (P = .010); more frequently presented with atrial fibrillation (P < .001), diabetes (P < .001), and impaired renal function (P < .001); and had higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (P < .001), larger left (P = .023) and right ventricles (RV; P = .002), and worse RV function (P < .001). Patients were followed for 17.8 months ± 12.9, during which 110 patients (16.9%) reached the primary end point. By Kaplan-Meier analysis, event-free survival was significantly worse in patients with a PA-to-Ao ratio of 1.0 or greater (log-rank test, P < .001). A PA-to-Ao ratio of 1.0 or greater was independently associated with outcome by multivariable Cox regression analysis, in addition to age, NT-proBNP serum levels, and RV size. Conclusion A PA-to-Ao ratio of 1.0 or greater identified patients at risk, most likely because of elevated PA pressures. On the basis of these results, the PA-to-Ao ratio should routinely be reported at cardiac MR imaging. © RSNA, 2017 Online supplemental material is available for this article.

Pulmonary artery to aorta ratio for the detection of pulmonary hypertension: cardiovascular magnetic resonance and invasive hemodynamics in heart failure with preserved ejection fraction.

BACKGROUND: Previous work indicates that dilatation of the pulmonary artery (PA) itself or in relation to the ascending aorta (PA:Ao ratio) predicts pulmonary hypertension (PH). Whether these results also apply for heart failure with preserved ejection fraction (HFpEF) is unknown. In the present study we evaluated the diagnostic and prognostic power of PA diameter and PA:Ao ratio on top of right ventricular (RV) size, function, and septomarginal trabeculation (SMT) thickness by cardiovascular magnetic resonance (CMR) in HFpEF. METHODS AND RESULTS: 159 consecutive HFpEF patients were prospectively enrolled. Of these, 111 underwent CMR and invasive hemodynamic evaluation. By invasive assessment 64 % of patients suffered from moderate/severe PH (mean pulmonary artery pressure (mPAP) ≥30 mmHg). Significant differences between groups with and without moderate/severe PH were observed with respect to PA diameter (30.9 ± 5.1 mm versus 26 ± 5.1 mm, p < 0.001), PA:Ao ratio (0.93 ± 0.16 versus 0.78 ± 0.14, p < 0.001), and SMT diameter (4.6 ± 1.5 mm versus 3.8 ± 1.2 mm; p = 0.008). The strongest correlation with mPAP was found for PA:Ao ratio (r = 0.421, p < 0.001). By ROC analysis the best cut-off for the detection of moderate/severe PH was found for a PA:Ao ratio of 0.83. Patients were followed for 22.0 ± 14.9 months. By Kaplan Meier analysis event-free survival was significantly worse in patients with a PA:Ao ratio ≥0.83 (log rank, p = 0.004). By multivariable Cox-regression analysis PA:Ao ratio was independently associated with event-free survival (p = 0.003). CONCLUSION: PA:Ao ratio is an easily measureable noninvasive indicator for the presence and severity of PH in HFpEF, and it is related with outcome.

Influence of drug adherence and medical care on heart failure outcome in the primary care setting in Austria.

PURPOSE: Guideline-recommended therapy has been proven beneficial in heart failure (HF), but general implementation remains poor. The aim of this study was to evaluate the adherence to drug therapy, quality of primary non-drug medical care (NDMC) and its impact on HF outcome. METHODS: From 13 Austrian health insurance funds, we identified 36 829 patients (77.1 ± 10.8 years, 44.8% men) hospitalised for HF who survived more than 90 days after discharge in the period between April 2006 and June 2010. Drug adherence was analysed from prescriptions filled and NDMC from numbers of physician consultations and diagnostic tests relevant for HF per quarter of a year (medical care index (MedCI)) claimed from the insurance funds. Kaplan-Meier and multivariate Cox regression analyses were performed to identify the association of outcome (survival and death without further admission for HF, readmission for HF) with drug adherence and NDMC. RESULTS: Readmission due to HF or death without prior readmission for HF occurred in 19.7% and 22.5%, respectively. Adherence to angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers, beta-blockers and aldosterone antagonists was 49.3%, 40.4% and 16.1%, respectively, and was associated with better survival by Kaplan-Meier analysis. NDMC was consumed less frequently by deceased (76.0%; MedCI 2.55 ± 3.04) than surviving (79.3%; 3.60 ± 3.81) or readmitted (78.4%; 3.80 ± 4.13) patients (p < 0.001 for deceased vs both other). Drug adherence and NDMC were independent factors associated with better survival by multivariate regression analysis. CONCLUSION: Guideline-recommended drug therapy remains underutilised in Austria. Drug adherence and quality of NDMC are associated with better outcome in HF patients.

Abnormal pulmonary arterial pressure limits exercise capacity in patients with COPD.

OBJECTIVE: Pulmonary hypertension (PH) is common in patients with chronic obstructive pulmonary disease (COPD). Mean pulmonary artery pressure (mPAP) is often only slightly elevated at rest but is increased by exercise. The purpose of this study was to determine whether abnormal pulmonary artery pressure impairs exercise capacity in patients with COPD. PATIENTS AND METHODS: 42 patients with moderate-to-very-severe COPD (28 men, 14 women) underwent symptom-limited incremental cardiopulmonary exercise testing and also right-heart catheterization at rest. Abnormal pulmonary artery pressure was defined as mPAP>20 mmHg at rest. RESULTS: Resting mPAP was elevated in 32 patients (PH, mPAP=26.8+/-5.9 mmHg) and normal in 10 non-hypertensive (NPH) patients (NPH, mPAP=16.8+/-2 mmHg). There were no significant differences in lung function between the PH and NPH groups. Maximum oxygen uptake during exercise (VO2max) was significantly lower in PH (785+/-244 ml/min) than in NPH (1052+/-207 ml/min, P=0.004). Dead-space ventilation (Vd/Vt) was greater in PH (P=0.05) with higher VE/VCO2 (ratio of minute ventilation to carbon dioxide output=47.3+/-10 vs 38.6+/-3.5, P=0.025) and significantly higher arterial-end-tidal pCO2 difference [p(a-ET)CO2]. Pulmonary vascular resistance measured at rest correlated significantly with VO2max, VE/VCO2 and p(a-ET)CO2. CONCLUSIONS: In patients with COPD, abnormal pulmonary artery pressure impairs gas exchange, decreases maximum oxygen uptake during exercise and impairs exercise capacity.

Extracellular volume quantification by cardiac magnetic resonance imaging without hematocrit sampling : Ready for prime time?

BACKGROUND: Myocardial tissue characterization by cardiovascular magnetic resonance (CMR) T1 mapping currently receives increasing interest as a diagnostic tool in various disease settings. The T1-mapping technique allows non-invasive estimation of myocardial extracellular volume (ECV) using T1-times before and after gadolinium administration; however, for calculation of the myocardial ECV the hematocrit is needed, which limits its utility in routine application. Recently, the alternative use of the blood pool T1-time instead of the hematocrit has been described. METHODS: The results of CMR T1 mapping data of 513 consecutive patients were analyzed for this study. Blood for hematocrit measurement was drawn when placing the i. v. line for contrast agent administration. Data from the first 200 consecutive patients (derivation cohort) were used to establish a regression formula allowing synthetic hematocrit calculation, which was then validated in the following 313 patients (validation cohort). Synthetic ECV was calculated using synthetic hematocrit, and was compared with conventionally derived ECV. RESULTS: Among the entire cohort of 513 patients (mean age 57.4 ± 17.5 years old, 49.1% female) conventionally measured hematocrit was 39.9 ± 4.7% and native blood pool T1-time was 1570.6 ± 117.8 ms. Hematocrit and relaxivity of blood (R1 = 1/blood pool T1 time) were significantly correlated (r = 0.533, r2 = 0.284, p < 0.001). By linear regression analysis, the following formula was developed from the derivation cohort: synthetic hematocrit = 628.5 × R1 - 0.002. Synthetic and conventional hematocrit as well as ECV showed significant correlation in the validation (r = 0.533, r2 = 0.284, p < 0.001 and r = 0.943, r2 = 0.889, p < 0.001, respectively) as well as the overall cohort (r = 0.552, r2 = 0.305, p < 0.001 and r = 0.957, r2 = 0,916, p < 0.001). By Bland Altman analysis, good agreement between conventional and synthetic ECV was found in the validation cohort (mean difference: 0.007%, limits of agreement: -4.32 and 4.33%, respectively). CONCLUSION: Synthetic ECV using native blood pool T1-times to calculate the hematocrit, is feasible and leads to almost identical results in comparison with the conventional method. It may allow fully automatic ECV-mapping and thus enable broader use of ECV by CMR T1 mapping in clinical practice.

Interstitial Fibrosis, Functional Status, and Outcomes in Heart Failure With Preserved Ejection Fraction: Insights From a Prospective Cardiac Magnetic Resonance Imaging Study.

BACKGROUND: Myocardial extracellular volume (ECV) accumulation is one of the key pathophysiologic features of heart failure with preserved ejection fraction (HFpEF). Our aims were to (1) measure ECV by cardiac magnetic resonance T1 mapping using the modified Look-Locker inversion recovery (MOLLI) sequence, (2) validate MOLLI-ECV against histology, and (3) investigate the relationship between MOLLI-ECV and prognosis in HFpEF. METHODS AND RESULTS: One-hundred seventeen consecutive HFpEF patients underwent cardiac magnetic resonance imaging, coronary angiography, and invasive hemodynamic assessments at baseline. Eighteen patients also underwent left ventricular biopsy for histological analysis (Histo-ECV). To assess the prognostic impact of MOLLI-ECV, its association with hospitalization for heart failure/cardiac death was tested by multivariable Cox regression analysis. Histo-ECV was 30.1±4.6% and was significantly correlated with MOLLI-ECV (R=0.494, P=0.037). Patients were followed for 24.0 months (6.0-32.0 months), during which 34 had a cardiac event. By Kaplan-Meier analysis, patients with MOLLI-ECV ≥ the median (28.9%) had shorter event-free survival (log-rank, P=0.028). MOLLI-ECV significantly correlated with N-terminal prohormone of brain natriuretic peptide (P<0.001), 6-minute walk distance (P=0.004), New York Heart Association functional class (P=0.009), right atrial pressure (P=0.037), and stroke volume (P=0.043). By multivariable Cox regression analysis, MOLLI-ECV was associated with outcome among imaging variables (P=0.038) but not after adjustment for clinical and invasive hemodynamic parameters. CONCLUSIONS: We demonstrate that MOLLI-ECV in HFpEF accurately reflects histological ECV, correlates with markers of disease severity, and is associated with outcome among cardiac magnetic resonance parameters but not after adjustment for important clinical and invasive hemodynamic parameters. Nevertheless, MOLLI-ECV has the potential of becoming an important biomarker in HFpEF.

Canine scent detection for the diagnosis of lung cancer in a screening-like situation.

The prognosis in lung cancer depends largely on early stage detection, and thus new screening methods are attracting increasing attention. Canine scent detection has shown promising results in lung cancer detection, but there has only been one previous study that reproduces a screening-like situation. Here breath samples were collected from 122 patients at risk for lung cancer (smokers and ex-smokers); 29 of the subjects had confirmed diagnosis of lung cancer but had not yet been treated and 93 subjects had no signs or symptoms of lung cancer at the time of inclusion. The breath samples were presented to a trained sniffer dog squadron in a double-blind manner. A rigid scientific protocol was used with respect to earlier canine scent detection studies, with one difference: instead of offering one in five positive samples to the dogs, we offered a random number of positive samples (zero to five). The final positive and negative predictive values of 30.9% and 84.0%, respectively, were rather low compared to other studies. The results differed from those of previous studies, indicating that canine scent detection might not be as powerful as is looked for in real screening situations. One main reason for the rather poor performance in our setting might be the higher stress from the lack of positive responses for dogs and handlers.

The right heart in heart failure with preserved ejection fraction: insights from cardiac magnetic resonance imaging and invasive haemodynamics.

AIMS: Recent data indicate that right ventricular systolic dysfunction (RVSD) by cardiac magnetic resonance imaging (CMR) is a strong predictor of outcome in heart failure. However, the prognostic significance of RVSD by CMR in heart failure with preserved ejection fraction (HFpEF) is unknown. METHODS AND RESULTS: We prospectively enrolled 171 HFpEF patients who underwent CMR in addition to invasive and non-invasive testing. RVSD, defined as right ventricular (RV) EF <45% by CMR, was present in 33 (19.3 %) patients. Patients were followed for 573 ± 387 days, during which 41 had a cardiac event. Patients with RVSD presented with more frequent history of AF (P = 0.038), significantly higher resting heart rate (P = 0.009), shorter 6-min walk distance (P = 0.036), and higher NT-pro BNP serum levels (P < 0.001), and were more symptomatic (P < 0.001). With respect to haemodynamic parameters, RVSD was associated with respect to haemodynamic parameters, RVSD was associated with higher diastolic pulmonary artery pressure (P = 0.045), with higher pulmonary vascular resistance (P = 0.048), higher transpulmonary gradient (P = 0.042), and higher diastolic pulmonary vascular pressure gradient (P = 0.007). In the multivariable Cox analysis, RVSD (P < 0.001) remained significantly associated with cardiac events, in addition to diabetes (P = 0.011), 6-min walk distance (P = 0.018), and systolic pulmonary artery pressure (P = 0.003). CONCLUSIONS: Although HFpEF is considered a disease of the left ventricle, respective imaging parameters are not related to outcome. In contrast, RVSD by CMR is independently associated with mortality and clinical status in these patients, and provides a useful tool for risk stratification.

T1 Mapping by CMR Imaging: From Histological Validation to Clinical Implication.

OBJECTIVES: The purpose of this study was to prospectively investigate the diagnostic and prognostic impact of cardiac magnetic resonance (CMR) T1 mapping and validate it against left ventricular biopsies. BACKGROUND: Extracellular volume (ECV) expansion is a key feature of heart failure. CMR T1 mapping has been developed as a noninvasive technique to estimate ECV; however, the diagnostic and prognostic impacts of this technique have not been well established. METHODS: A total of 473 consecutive patients referred for CMR (49.5% female, age 57.8 ± 17.1 years) without hypertrophic cardiomyopathy, cardiac amyloidosis, or Anderson-Fabry disease were studied. T1 mapping with the modified Look-Locker inversion recovery (MOLLI) sequence was used for ECV calculation (CMR-ECV). For methodological validation, 36 patients also underwent left ventricular biopsy, and ECV was quantified by TissueFAXS analysis (TissueFAXS-ECV). To assess the prognostic value of CMR-ECV, its association with hospitalization for cardiovascular reasons or cardiac death was tested in a multivariable Cox regression model. RESULTS: TissueFAXS-ECV was 26.3 ± 7.2% and was significantly correlated with CMR-ECV (r = 0.493, p = 0.002). Patients were followed up for 13.3 ± 9.0 months and divided into CMR-ECV tertiles for Kaplan-Meier analysis (tertiles were ≤ 25.7%, 25.8% to 28.5%, and ≥ 28.6%). Significantly higher event rates were observed in patients with higher CMR-ECV (log-rank p = 0.013). By multivariable Cox regression analysis, CMR-ECV was independently associated with outcome among imaging variables (p = 0.004) but not after adjustment for clinical parameters. CONCLUSIONS: CMR T1 mapping allows accurate noninvasive quantification of ECV and is independently associated with event-free survival among imaging parameters. Its prognostic value on top of established clinical risk factors warrants further investigation in long-term studies.

Long-Term Outcome of Combined (Percutaneous Intramyocardial and Intracoronary) Application of Autologous Bone Marrow Mononuclear Cells Post Myocardial Infarction: The 5-Year MYSTAR Study.

OBJECTIVE: The long-term (5-year) outcome of early (3-6 weeks after acute myocardial infarction [AMI], BM-MNC Early group) and late (3-4 months after AMI, BM-MNC Late group) combined (percutaneous intramyocardial and intracoronary) delivery of autologous bone marrow mononuclear cells (BM-MNCs) was evaluated in patients with ejection fractions (EF) between 30-45% post-AMI. METHODS: Major adverse cardiac and cerebrovascular events (MACCE) and hospitalization were recorded. Left (LV) and right (RV) ventricular function were measured by transthoracic echocardiography. Cardiac magnetic resonance imaging (MRI) and myocardial single photon emission computed tomography was performed in a subgroup of patients. Pre-cell therapy myocardial voltage values of treated areas (assessed by NOGA mapping) were correlated with clinical outcome. RESULTS: Five-year MACCE incidences (7.4%. vs 24.1%) and the composite of all adverse events (11.1% vs 27.6%) were not different between the Early and Late treatment groups. The significant LV-EF increase at 1-year follow-up was preserved at the 5-year control (from baseline to 5-year: 5.3%, 95% CI:0.5-10.1, and 5.7%, 95% CI:1.7-9.6, p<0.05 in the Early and Late groups, respectively), with no significant changes between 1- and 5-year follow-ups. Similarly, RVEF increased significantly from baseline to the 5-year follow-up (Early group: 5.4%, 95% CI:1.0-9.6; and Late group: 8.4%, 95% CI:4.5-12.3). Lower baseline levels of myocardial viability of the treated cardiac area (6.3±2.4 vs 8.2±3.0 mV, p<0.05) were associated with incidence of MACCE. CONCLUSIONS: Percutaneous combined delivery of autologous BM-MNCs is feasible and safe after 5 years, and may result in sustained improvement of cardiac function at 5 years in patients with low EF post-AMI (Clinicaltrials.gov NCT01395212).

Prognostic Impact of Tricuspid Regurgitation in Patients Undergoing Aortic Valve Surgery for Aortic Stenosis.

BACKGROUND: The prognostic significance of tricuspid regurgitation (TR) and right ventricular (RV) function in patients undergoing aortic valve replacement (AVR) for severe aortic stenosis (AS) is unknown. The aim of the present study was to evaluate the impact of TR and RV systolic dysfunction on early and late mortality in this setting. METHODS: This was a prospective single-center observational study. 465 consecutive patients who were referred to AVR for severe AS were investigated. Significant TR was defined as TR≥moderate by transthoracic echocardiography. RESULTS: At baseline, significant TR was present in 26 (5.6%) patients. Patients with TR presented with a higher EuroSCORE I (p = 0.001), a higher incidence of previous cardiac surgery (p<0.001), pulmonary hypertension (p = 0.003), more dilated RVs (p = 0.001), and more frequent RV dysfunction (p = 0.001). Patients were followed for an average of 5.2 (±2.8 SD) years. By multivariable Cox regression analysis TR (p = 0.014), RV dysfunction (p = 0.046), age (p = 0.001) and concomitant coronary artery bypass graft surgery (CABG, p = 0.003) were independently associated with overall mortality. By Kaplan-Meier analysis, survival rates were significantly worse in patients with significant than with non-significant TR (log rank p = 0.001). CONCLUSIONS: TR, RV dysfunction, age, and concomitant CABG are associated with outcome in patients undergoing AVR for severe AS. This finding underlines the importance of a thorough echocardiographic evaluation with particular consideration of the right heart in these patients.

The anticipation and management of air leaks and residual spaces post lung resection.

The incidence of any kind of air leaks after lung resections is reportedly around 50% of patients. The majority of these leaks doesn't require any specific intervention and ceases within a few hours or days. The recent literature defines a prolonged air leak (PAL) as an air leak lasting beyond postoperative day 5. PAL is associated with a generally worse outcome with a more complicated postoperative course anxd prolonged hospital stay and increased costs. Some authors therefore consider any PAL as surgical complication. PAL is the most prevalent postoperative complication following lung resection and the most important determinant of postoperative length of hospital stay. A low predicted postoperative forced expiratory volume in 1 second (ppoFEV1) and upper lobe disease have been identified as significant risk factors involved in developing air leaks. Infectious conditions have also been reported to increase the risk of PAL. In contrast to the problem of PAL, there is only limited information from the literature regarding apical spaces after lung resection, probably because this common finding rarely leads to clinical consequences. This article addresses the pathogenesis of PAL and apical spaces, their prediction, prevention and treatment with a special focus on surgery for infectious conditions. Different predictive models to identify patients at higher risk for the development of PAL are provided. The discussion of surgical treatment options includes the use of pneumoperitoneum, blood patch, intrabronchial valves (IBV) and the flutter valve, and addresses the old question, whether or not to apply suction to chest tubes. The discussed prophylactic armentarium comprises of pleural tenting, prophylactic intraoperative pneumoperitoneum, sealing of the lung, buttressing of staple lines, capitonnage after resection of hydatid cysts, and plastic surgical options.

Right ventricular dysfunction, but not tricuspid regurgitation, is associated with outcome late after left heart valve procedure.

BACKGROUND: Significant tricuspid regurgitation (TR) late after left heart valve procedure is frequent and associated with increased morbidity. Surgical correction carries a significant mortality risk, whereas the impact of TR on survival in these patients is unclear. OBJECTIVES: This study sought to assess the impact of significant TR late after left heart valve procedure. METHODS: A total of 539 consecutive patients with previous left heart valve procedure (time interval from valve procedure to enrollment 50 ± 30 months) were prospectively followed for 53 ± 15 months. RESULTS: Significant TR (defined as moderate or greater severity by echocardiography) was present in 91 (17%) patients (65% female). Patients with TR presented with more symptoms (New York Heart Association functional class ≥II 55% vs. 31%), lower glomerular filtration rates (61 ± 19 ml/min vs. 68 ± 18 ml/min), and a higher likelihood of atrial fibrillation (41% vs. 20%), all statistically significant. Right ventricular (RV) systolic function was worse in patients with significant TR (RV fractional area change 43 ± 11% vs. 47 ± 9%, p < 0.001). A total of 117 (22%) patients died during follow-up. By Kaplan-Meier analysis, overall survival was significantly worse in patients with significant TR (log-rank p < 0.001). However, by multivariable Cox analysis, only RV fractional area change, age, left atrial size, diabetes, and previous coronary artery bypass graft procedure were significantly associated with mortality, but not tricuspid regurgitation. CONCLUSIONS: RV dysfunction, but not significant TR, is independently associated with survival late after left heart valve procedure.

Measurement of retinal oxygen saturation in patients with chronic obstructive pulmonary disease.

PURPOSE: There is growing evidence that disturbances in retinal oxygenation may trigger ocular diseases. New instruments allow for the noninvasive measurement of retinal oxygen saturation in humans. The present study was designed to investigate the retinal oxygen saturation in patients with chronic obstructive pulmonary disease (COPD). This was also done in an effort to test the validity of retinal oxygenation measurements with a retinal vessel analyzer. METHODS: In all, 16 patients with severe COPD grade 4 who were on long-term oxygen treatment were included in the study. For each patient two identical study days were scheduled. Measurements of retinal arterial and venous oxygen saturation were done using a commercially available instrument for retinal oxygen analysis. Peripheral arterial oxygen saturation values were analyzed with pulse oximetry and via a capillary blood sample drawn from the earlobe. Measurements were performed during oxygen treatment and during a period without oxygen supplementation. Analysis of all images for retinal oxygen saturation quantification was done by a masked investigator. Analysis was done using Pearson's correlation and a multivariate regression model. RESULTS: Arterial and venous retinal oxygen saturation decreased significantly after the cessation of the oxygen therapy. The arteriovenous oxygen difference was unchanged while breathing ambient air or pure oxygen-enriched air. With both Pearson's correlation and the multivariate model, we found significant positive correlation coefficients between retinal arterial and peripheral arterial oxygen saturation as assessed with pulse oximetry as well as between retinal arterial and peripheral arterial oxygen saturation measured in blood samples. The change of oxygen saturation after discontinuation of oxygen supplementation showed a good correlation between retinal arterial oxygen saturation and peripheral arterial oxygen saturation (r = 0.53, P < 0.05). Reproducibility on the two study days was high. DISCUSSION: The present study shows a good correlation between retinal arterial and peripheral arterial oxygen saturation indicating good validity of the technique. (ClinicalTrials.gov number, NCT00999024.).

Cardiac magnetic resonance postcontrast T1 time is associated with outcome in patients with heart failure and preserved ejection fraction.

BACKGROUND: The underlying pathophysiology of heart failure with preserved ejection fraction (HFPEF) is incompletely understood, but myocardial extracellular matrix accumulation is thought to play a major role. Our aims were to estimate myocardial extracellular matrix using cardiac magnetic resonance T1 mapping and to assess the relationship between pathobiology/pathophysiology and prognosis. METHODS AND RESULTS: Patients with suspected HFPEF (n=100) were enrolled in this prospective, observational study. Confirmatory diagnostic tests, cardiac magnetic resonance imaging including T1 mapping, and invasive hemodynamic assessments were performed at baseline. Sixty-one patients with confirmed HFPEF entered a longitudinal outcome-monitoring phase (mean, 22.9±5.0 months), during which 16 had a cardiac event. Cardiac magnetic resonance T1 time (hazard ratio, 0.99; 95% confidence interval, 0.98-0.99; P=0.046), left atrial area (hazard ratio, 1.08; 95% confidence interval, 1.03-1.13; P<0.01), and pulmonary vascular resistance (hazard ratio, 1.01; 95% confidence interval, 1.00-1.01; P=0.03) were significantly associated with cardiac events. Patients with T1 times below the median (<388.3 ms) were at greater risk of cardiac events than the rest of the group (P<0.01). Extracellular matrix of left ventricular biopsies (n=9), quantified by TissueFAXS technology correlated with T1 time (R=0.98; P<0.01). T1 time also correlated with right ventricular-pulmonary arterial coupling (pulmonary vascular resistance: R=-0.36; P<0.01; right ventricular ejection fraction: R=0.28; P=0.01). CONCLUSIONS: In the present preliminary study, cardiac magnetic resonance postcontrast T1 time is associated with prognosis in HFPEF, suggesting postcontrast T1 as possible biomarker for HFPEF.

Strength training increases maximum working capacity in patients with COPD--randomized clinical trial comparing three training modalities.

BACKGROUND AND OBJECTIVE: Skeletal muscle dysfunction contributes to exercise limitation in patients with chronic obstructive pulmonary disease (COPD). Strength training increases muscle strength and muscle mass, but there is an ongoing debate on the additional effect concerning the exercise capacity. The purpose of this study was to compare the effects of three different exercise modalities in patients with COPD including endurance training (ET), progressive strength training (ST) and the combination of strength training and endurance training (CT). DESIGN: A prospective randomized trial. METHODS: Thirty-six patients with COPD were randomly allocated either to ET, ST, or CT. Muscle strength, cardiopulmonary exercise testing, lung function testing and quality of life were assessed before and after a 12-week training period. RESULTS: Exercise capacity (Wmax) increased significantly in all three training groups with increase of peak oxygen uptake (VO2peak) in all three groups, reaching statistical significance in the ET group and the CT group. Muscle strength (leg press, bench press, bench pull) improved in all three training groups, with a higher improvement in the ST (+39.3%, +20.9%, +20.3%) and the CT group (+43.3%, +18.1%, +21.6%) compared to the ET group (+20.4%, +6.4%, +12.1%). CONCLUSIONS: Progressive strength training alone increases not only muscle strength and quality of life, but also exercise capacity in patients with COPD, which may have implications in prescription of training modality. CLINICALTRIALS.GOV IDENTIFIER: NCT01091623.

Vasoactive intestinal peptide (VIP) receptor expression in monocyte-derived macrophages from COPD patients.

Vasoactive intestinal peptide (VIP) is one of the most abundant molecules found in the respiratory tract. Due to its anti-inflammatory and bronchodilatatory properties, it has been proposed as a novel treatment for chronic obstructive pulmonary disease (COPD). The actions of VIP are mediated via three different G-protein-coupled receptors (VPAC1, VPAC2 and PAC1) which are expressed in the respiratory tract and on immunocompetent cells including macrophages. Alveolar macrophages (AM) are key players in the pathogenesis of COPD and contribute to the severity and progression of the disease. While VPAC1 has been reported to be elevated in subepithelial cells in smokers with chronic bronchitis, little is known about VPAC expression of AM in COPD patients. AM from COPD patients show a strong VPAC1 expression which exceeds VPAC2. A similar receptor expression pattern was also observed in lipopolysaccharide (LPS)-activated monocyte-derived macrophages (MDM) from healthy volunteers and COPD patients. VIP has been shown to down-regulate interleukin 8 (IL-8) secretion significantly in MDM after LPS stimulation. The response to VIP was similar in MDM from COPD patients and healthy volunteers. Our results indicate that VPAC1 up-regulation in macrophages is a common mechanism in response to acute and chronic pro-inflammatory stimuli. Although VPAC1 up-regulation is dominant, both receptor subtypes are necessary for optimal anti-inflammatory signaling. The high VPAC1 expression in AM may reflect the chronic pro-inflammatory environment found in the lung of COPD patients. Treatment with VIP may help to decrease the chronic inflammation in the lung of COPD patients.