TY - JOUR T1 - Regresión Logística No Condicionada Y Tamaño De Muestra: Una Revisión Bibliográfica A1 - Ortega, M. A1 - Cayuela, A Y1 - 2002/// KW - análisis cualitativo KW - ciencias de la KW - ciencias sociales KW - epistemología KW - evaluación de la calidad KW - investigación cualitativa KW - metodología KW - salud JF - Revista Española de Salud PÚblica VL - 76 IS - 2 SP - 85 EP - 93 L1 - file:///C:/Users/fandinoc/OneDrive - Merck Sharp & Dohme, Corp/PERSONAL/PERSONAL/TESIS/BOBLIOGRAFIA ADICIONAL/regresion logistica no condicionada.pdf N2 - Unconditioned Logistic Regression and Sample Size: A Reference Source Review Unconditioned logistic regression is a highly useful risk prediction method in epidemiology. This article reviews the different solutions provided by different authors concerning the interface between the calculation ofthe sample size and the use oflogistics regression. Based on the knowledge ofthe informa- tion initially provided, a review is made of the customized re- gression and predictive constriction phenomenon, the design of an ordinal exposition with a binary output, the event of interest per variable concept, the indicator variables, the classic Free- man equation, etc. Some skeptical ideas regarding this subject are ER - TY - JOUR T1 - Arterial blood gas reference values for sea level and an altitude of 1,400 meters A1 - Crapo, Robert O. A1 - Jensen, Robert L. A1 - Hegewald, Mathew A1 - Tashkin, Donald P. Y1 - 1999/// JF - American Journal of Respiratory and Critical Care Medicine VL - 160 IS - 5 I SP - 1525 EP - 1531 DO - 10.1164/ajrccm.160.5.9806006 L1 - file:///C:/Users/fandinoc/OneDrive - Merck Sharp & Dohme, Corp/PERSONAL/PERSONAL/TESIS/BOBLIOGRAFIA ADICIONAL/Arterial bllod gas reference values for sea level.pdf N2 - Blood gas measurements were collected on healthy lifetime nonsmokers at sea level (n = 96) and at an altitude of 1,400 meters (n = 243) to establish reference equations. At each study site, arterial blood samples were analyzed in duplicate on two separate blood gas analyzers and CO-oximeters. Arterial blood gas variables included Pa(O2), Pa(CO2), pH, and calculated alveolar- arterial Po2 difference (AaPo2). CO-oximeter variables were Hb, COHb, MetHb, and Sa(O2). Subjects were 18 to 81 yr of age with 166 male and 173 female. Outlier data were excluded from multiple regression analysis, and reference equations were fitted to the data in two ways: (1) best fit using linear, squared, and cross-product terms; (2) simple equations, including only the variables that explained at least 3% of the variance. Two sets of equations were created: (1) using only the sea level data and (2) using the combined data with barometric pressure as an independent variable. Comparisons with earlier studies revealed small but significant differences; the decline in Pa(O2) with age at each altitude was consistent with most previous studies. At sea level, the equation that included barometric pressure predicted Pa(O2) slightly better than the sea level specific equation. The inclusion of barometric pressure in the equations allows better prediction of blood gas reference values at sea level and at altitudes as high as 1,400 meters. ER - TY - JOUR T1 - Living the high life : high-altitude adaptation A1 - Scheinfeldt, Laura B A1 - Tishko, Sarah A Y1 - 2010/// SP - 9 EP - 11 L1 - file:///C:/Users/fandinoc/OneDrive - Merck Sharp & Dohme, Corp/PERSONAL/PERSONAL/TESIS/BOBLIOGRAFIA ADICIONAL/Living the high life high altitude adaptation.pdf ER - TY - JOUR T1 - The 6-min walk distance in healthy subjects: Reference standards from seven countries A1 - Casanova, C. A1 - Celli, B. R. A1 - Barria, P. A1 - Casas, A. A1 - Cote, C. A1 - De Torres, J. P. A1 - Jardim, J. A1 - Lopez, M. V. A1 - Marin, J. M. A1 - Montes De Oca, M. A1 - Pinto-Plata, V. A1 - Aguirre-Jaime, A. Y1 - 2011/// KW - 6-min walk test KW - Geographic variability KW - Healthy subjects KW - Reference values JF - European Respiratory Journal VL - 37 IS - 1 SP - 150 EP - 156 DO - 10.1183/09031936.00194909 L1 - file:///C:/Users/fandinoc/OneDrive - Merck Sharp & Dohme, Corp/PERSONAL/PERSONAL/TESIS/BOBLIOGRAFIA ADICIONAL/The 6min walk distance in healthy subjects reference standards from seven countries.pdf N2 - The 6-min walk distance (6MWD) predicted values have been derived from small cohorts mostly from single countries. The aim of the present study was to investigate differences between countries and identify new reference values to improve 6MWD interpretation. We studied 444 subjects (238 males) from seven countries (10 centres) ranging 40-80 yrs of age. We measured 6MWD, height, weight, spirometry, heart rate (HR), maximum HR (HRmax) during the 6-min walk test/the predicted maximum HR (HRmax % pred), Borg dyspnoea score and oxygen saturation. The mean±SD 6MWD was 571±90 m (range 380-782 m). Males walked 30 m more than females (p<0.001). A multiple regression model for the 6MWD included age, sex, height, weight and HRmax % pred (adjusted r2=0.38; p<0.001), but there was variability across centres (adjusted r2=0.09-0.73) and its routine use is not recommended. Age had a great impact in 6MWD independent of the centres, declining significantly in the older population (p<0.001). Age-specific reference standards of 6MWD were constructed for male and female adults. In healthy subjects, there were geographic variations in 6MWD and caution must be taken when using existing predictive equations. The present study provides new 6MWD standard curves that could be useful in the care of adult patients with chronic diseases. Copyright©ERS 2011. ER - TY - JOUR T1 - Heart rate recovery predicts clinical worsening in patients with pulmonary arterial hypertension A1 - Minai, Omar A. A1 - Gudavalli, Ravi A1 - Mummadi, Srinivas A1 - Liu, Xiaobo A1 - McCarthy, Kevin A1 - Dweik, Raed A. Y1 - 2012/// KW - 6-minute walk KW - Clinical worsening KW - Heart rate KW - Pulmonary hypertension KW - Survival JF - American Journal of Respiratory and Critical Care Medicine VL - 185 IS - 4 SP - 400 EP - 408 DO - 10.1164/rccm.201105-0848OC L1 - file:///C:/Users/fandinoc/OneDrive - Merck Sharp & Dohme, Corp/PERSONAL/PERSONAL/TESIS/BOBLIOGRAFIA ADICIONAL/HEART RATE RECOVERY PREDICTS CLINICAL WORSENING IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION.pdf N2 - Rationale: Reduced heart rate recovery after exercise is associated with increased mortality in cardiopulmonary diseases. Objectives: We sought to evaluate the association between heart rate recovery at 1 minute of rest (HRR1) after 6-min walk test (6MW test) and clinical worsening in patients with idiopathic pulmonary arterial hypertension (IPAH). Methods: HRR1 was defined as the difference in heart rate at the end of 6MW test and at 1 minute after completion of the 6MW test. Between August 1, 2009 and March 30, 2010, 75 consecutive patients with IPAH underwent 6MW test and were included in the analysis. Measurements and Main Results: Comparedwith patients with HRR1 ≥16 (n = 45 [60%]), those with HRR1 less than 16 (n = 30 [40%]) were more likely to have clinical worsening (odds ratio, 9.7; 95% confidence interval [CI], 3-30; P < 0.001) and shorter time to first clinical worsening event (TCW) (6.7 mo vs. 13 mo; P < 0.001) during follow-up. By multivariable analysis, the best predictors of clinical worsening were HRR1 less than 16 (hazard ratio, 5.2; 95% CI, 1.8-14.8; P = 0.002) and mean pulmonary arterial pressure (hazard ratio, 1.04; 95% CI, 1.007-1.08; P = 0.02). Compared with the distance walked during the 6MW test (6MWD), HRR1 less than 16 was a better predictor of clinical worsening (C statistic 0.757 vs. 0.703) and TCW (C index 0.730 vs. 0.696). The addition of HRR1 increased the ability of 6MWD to predict clinical worsening events. Conclusions: HRR1 after 6MW test is a strong predictor of clinical worsening and TCW in patients with IPAH. The addition of HRR1 to 6MWD increases the capacity of6MWD to predict clinical worsening and TCW in patients with IPAH. Copyright © 2012 by the American Thoracic Society. ER - TY - JOUR T1 - Epidemiology and treatment of pulmonary arterial hypertension A1 - Lau, Edmund M.T. A1 - Giannoulatou, Eleni A1 - Celermajer, David S. A1 - Humbert, Marc Y1 - 2017/// PB - Nature Publishing Group JF - Nature Reviews Cardiology VL - 14 IS - 10 SP - 603 EP - 614 DO - 10.1038/nrcardio.2017.84 UR - http://dx.doi.org/10.1038/nrcardio.2017.84 L1 - file:///C:/Users/fandinoc/OneDrive - Merck Sharp & Dohme, Corp/PERSONAL/PERSONAL/TESIS/BOBLIOGRAFIA ADICIONAL/Epidemiology and treatment of pulmonary arterial hypertension.pdf N2 - In the past 2 decades, major changes have occurred in the epidemiological and treatment landscape of pulmonary arterial hypertension (PAH). Previously regarded as a disease of the young and middle-aged, contemporary registries from the Western world have demonstrated an increase in the age of patients with PAH, many of whom are elderly with multiple comorbidities. Another important observation is the improvement in survival of patients with PAH in the modern treatment era compared with historical cohorts, before the availability of advanced therapy. The management of PAH has also become more complex, and numerous drugs are now approved that target the endothelin 1, nitric oxide, and prostacyclin pathways. Combining drugs from different classes is now considered the standard of care and has been demonstrated to improve outcomes. Furthermore, the current treatment paradigm is the early use of combination therapy, often at the time of diagnosis, particularly in patients with severe disease. This Review provides a comprehensive update on the epidemiology and pharmacotherapy of PAH. ER - TY - JOUR T1 - Use of supplemental oxygen in patients with pulmonary arterial hypertension in REVEAL A1 - Farber, Harrison W. A1 - Badesch, David B. A1 - Benza, Raymond L. A1 - Elliott, C. Gregory A1 - Frantz, Robert P. A1 - McGoon, Michael D. A1 - Selej, Mona A1 - Zhao, Carol A1 - Frost, Adaani E. Y1 - 2018/// KW - diffusing capacity of lungs for carbon monoxide (D KW - long-term oxygen therapy, pulmonary arterial hyper KW - pulmonary hypertension KW - pulmonary vascular disease KW - supplemental oxygen PB - Elsevier Inc. JF - Journal of Heart and Lung Transplantation VL - 37 IS - 8 SP - 948 EP - 955 DO - 10.1016/j.healun.2018.03.010 UR - http://dx.doi.org/10.1016/j.healun.2018.03.010 L1 - file:///C:/Users/fandinoc/OneDrive - Merck Sharp & Dohme, Corp/PERSONAL/PERSONAL/TESIS/BOBLIOGRAFIA ADICIONAL/Use of supplemental oxygen in patients with pulmonary arterial hypertension in REVEAL.pdf N2 - Background: Supplemental low-flow oxygen is recommended by treatment guidelines as supportive therapy for patients with pulmonary arterial hypertension (PAH), based largely on expert opinion. Reduced diffusing capacity of lung carbon monoxide (DLCO) is associated with increased mortality in PAH. Reduced DLCO is also associated with relative hypoxemia, making the effects of supplemental oxygen use of particular interest in this sub-population. Methods: Patients in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a 5-year observational study of Group 1 PAH, were categorized by presence or absence of supplemental oxygen use and by degree of DLCO reduction. Kaplan–Meier survival estimates were calculated by group. Results: Of 3,046 patients, 57% used supplemental oxygen and 43% did not. Supplemental oxygen users had worse prognostic factors and more PAH-specific medication use. Of the 424 patients with severe DLCO reduction (<40% of predicted), 76% used oxygen and 24% did not. Patients with severe DLCO reduction who used supplemental oxygen had a significantly lower risk of all-cause mortality than those who did not (hazard ratio 0.56; 95% confidence interval 0.39 to 0.83; p = 0.0033). This was true for newly diagnosed and previously diagnosed patients. There was no relationship between oxygen use and outcomes in patients with no, mild, or moderate DLCO reduction. Conclusions: In this observational study, the risk of death was significantly lower for patients with severe DLCO reduction who received supplemental oxygen compared with those who did not. A randomized trial is warranted to further investigate the relationship between supplemental oxygen use and outcomes in PAH. ER - TY - JOUR T1 - Mortality in pulmonary arterial hypertension: Prediction by the 2015 European pulmonary hypertension guidelines risk stratification model A1 - Hoeper, Marius M. A1 - Kramer, Tilmann A1 - Pan, Zixuan A1 - Eichstaedt, Christina A. A1 - Spiesshoefer, Jens A1 - Benjamin, Nicola A1 - Olsson, Karen M. A1 - Meyer, Katrin A1 - Vizza, Carmine Dario A1 - Vonk-Noordegraaf, Anton A1 - Distler, Oliver A1 - Opitz, Christian A1 - Gibbs, J. Simon R. A1 - Delcroix, Marion A1 - Ghofrani, H. Ardeschir A1 - Huscher, Doerte A1 - Pittrow, David A1 - Rosenkranz, Stephan A1 - Grünig, Ekkehard Y1 - 2017/// JF - European Respiratory Journal VL - 50 IS - 2 SP - 1 EP - 10 DO - 10.1183/13993003.00740-2017 UR - http://dx.doi.org/10.1183/13993003.00740-2017 L1 - file:///C:/Users/fandinoc/OneDrive - Merck Sharp & Dohme, Corp/PERSONAL/PERSONAL/TESIS/BOBLIOGRAFIA ADICIONAL/Mortality in pulmonary arterial hypertension.pdf N2 - The 2015 European pulmonary hypertension (PH) guidelines propose a risk stratification strategy for patients with pulmonary arterial hypertension (PAH). Low-, intermediate- and high-risk strata are defined by estimated 1-year mortality risks of <5%, 5-10% and >10%, respectively. This risk assessment strategy awaits validation. We analysed data from patients with newly diagnosed PAH enrolled into COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension), a European-based PH registry. An abbreviated version of the risk assessment strategy proposed by the European PH guidelines was applied, using the following variables: World Health Organization functional class, 6-min walking distance, brain natriuretic peptide or its N-terminal fragment, right atrial pressure, cardiac index and mixed venous oxygen saturation. Data from 1588 patients were analysed. Mortality rates were significantly different between the three risk strata (p<0.001 for all comparisons). In the entire patient population, the observed mortality rates 1 year after diagnosis were 2.8% in the low-risk cohort (n=196), 9.9% in the intermediate-risk cohort (n=1116) and 21.2% in the high-risk cohort (n=276). In addition, the risk assessment strategy proved valid at follow-up and in major PAH subgroups. An abbreviated version of the risk assessment strategy proposed by the current European PH guidelines provides accurate mortality estimates in patients with PAH. ER - TY - JOUR T1 - WHO Group I Pulmonary Hypertension: Epidemiology and Pathophysiology A1 - Thenappan, Thenappan A1 - Prins, Kurt W. Y1 - 2017/// KW - endothelium KW - estrogen KW - estrogen receptors KW - vascular smooth muscle JF - Cardiol Clin. VL - 34 IS - 3 SP - 363 EP - 374 DO - 10.1016/j.ccl.2016.04.001.WHO L1 - file:///C:/Users/fandinoc/OneDrive - Merck Sharp & Dohme, Corp/PERSONAL/PERSONAL/TESIS/BOBLIOGRAFIA ADICIONAL/World Health Organization Group I Pulmonary Hypertension.pdf N2 - Pulmonary arterial hypertension (PAH) is a debilitating disease characterized by pathological remodeling of the resistance pulmonary arteries, ultimately leading to right ventricular (RV) failure and death [1]. In this review, we discuss the definition of PAH, the initial epidemiology based on the NIH Registry and the updated epidemiology gleaned from contemporary registries, pathogenesis of pulmonary vascular dysfunction and proliferation, and RV failure in PAH. ER - TY - JOUR T1 - THE TERMINAL PORTION OF THE PULMONARY ARTERIAL TREE IN PEOPLE NATIVE TO HIGH ALTITUDES. A1 - ARIAS-STELLA, J. A1 - SALDANA, M. Y1 - 1963/// JF - Circulation VL - 28 SP - 915 EP - 925 DO - 10.1161/01.CIR.28.5.915 ER - TY - JOUR T1 - Clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for pulmonary arterial hypertension within their licensed indications: a systematic review and economic evaluation. A1 - Chen, Y. F. A1 - Jowett, S. A1 - Barton, P. A1 - Malottki, K. A1 - Hyde, C. A1 - Gibbs, J. S. A1 - Pepke-Zaba, J. A1 - Fry-Smith, A. A1 - Roberts, J. A1 - Moore, D. Y1 - 2009/// JF - Health technology assessment (Winchester, England) VL - 13 IS - 49 SP - 1 EP - 320 SN - 2046-4924; 1366-5278 DO - 10.3310/hta13490 N2 - OBJECTIVE(S): To investigate the clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for the treatment of adults with pulmonary arterial hypertension (PAH) within their licensed indications. DATA SOURCES: Major electronic databases (including the Cochrane Library, MEDLINE and EMBASE) were searched up to February 2007. Further data were obtained from dossiers submitted to NICE by the manufacturers of the technologies. REVIEW METHODS: The systematic clinical and economic reviews were conducted according to accepted procedures. Model-based economic evaluations of the cost-effectiveness of the technologies from the perspective of the UK NHS and personal social services were carried out. RESULTS: In total, 20 randomised controlled trials (RCTs) were included in this assessment, mostly of 12-18 weeks duration and comparing one of the technologies added to supportive treatment with supportive treatment alone. Four published economic evaluations were identified. None produced results generalisable to the NHS. There was no consensus in the industry submissions on the most appropriate model structure for the technology assessment. Improvement in 6-minute walk distance (6MWD) was seen with intravenous epoprostenol in primary pulmonary hypertension (PPH) patients with mixed functional class (FC) (mainly III and IV, licensed indication) compared with supportive care (58 metres; 95% CI 6-110). For bosentan compared with supportive care, the pooled result for improvement in 6MWD for FCIII patients with mixed PAH (licensed indication) was 59 metres (95% CI 20-99). For inhaled iloprost, sitaxentan and sildenafil no stratified data for improvement in 6MWD were available. The odds ratio (OR) for FC deterioration at 12 weeks was 0.40 (95% CI 0.13-1.20) for intravenous epoprostenol compared with supportive care. The corresponding values for inhaled iloprost (FCIII PPH patients; licensed indication), bosentan, sitaxentan (FCIII patients with mixed PAH; licensed indication) and sildenafil (FCIII patients with mixed PAH; licensed indication) were 0.29 (95% CI 0.07-1.18), 0.21 (95% CI 0.03-1.76), 0.18 (95% CI 0.02-1.64) and [Commercial-in-confidence information has been removed] respectively. The incremental cost-effectiveness ratios (ICERs) for the technologies plus supportive care compared with supportive care alone, determined by independent economic evaluation, were 277,000 pounds/quality-adjusted life-year (QALY) for FCIII and 343… ER - TY - JOUR T1 - ATS statement: Guidelines for the six-minute walk test A1 - Crapo, Robert O. A1 - Casaburi, Richard A1 - Coates, Allan L. A1 - Enright, Paul L. A1 - MacIntyre, Neil R. A1 - McKay, Roy T. A1 - Johnson, Douglas A1 - Wanger, Jack S. A1 - Zeballos, R. Jorge A1 - Bittner, Vera A1 - Mottram, Carl Y1 - 2002/// JF - American Journal of Respiratory and Critical Care Medicine VL - 166 IS - 1 SP - 111 EP - 117 SN - 1073-449X (Print)\r1073-449X (Linking) DO - 10.1164/rccm.166/1/111 N2 - This statement provides practical guidelines for the 6-minute walk test (6MWT). Specifically, it reviews indications, details factors that influence results, presents a brief step-by-step protocol, outlines safety measures, describes proper patient preparation and procedures, and offers guidelines for clinical interpretation of results. These recommendations are not intended to limit the use of alternative protocols for research studies. We do not discuss the general topic of clinical exercise testing. As with other American Thoracic Society statements on pulmonary function testing, these guidelines come out of a consensus conference. Drafts were prepared by two members (P.L.E. and R.J.Z.) and were based on a comprehensive Medline literature search from 1970 through 2001, augmented by suggestions from other committee members. Each draft responded to comments from the working committee. The guidelines follow previously published methods as closely as possible and provide a rationale for each specific recommendation. The final recommendations represent a consensus of the committee. The committee recommends that these guidelines be reviewed in five years and in the meantime encourages further research in areas of controversy. ER - TY - JOUR T1 - Hypoxic pulmonary vasoconstriction in cardiothoracic surgery: basic mechanisms to potential therapies. A1 - Tsai, Ben M A1 - Wang, Meijing A1 - Turrentine, Mark W A1 - Mahomed, Yousuf A1 - Brown, John W A1 - Meldrum, Daniel R Y1 - 2004/// JF - The Annals of thoracic surgery VL - 78 IS - 1 SP - 360 EP - 8 DO - 10.1016/j.athoracsur.2003.11.035 N2 - Hypoxic pulmonary vasoconstriction is postulated to be an adaptive mechanism to match lung perfusion with ventilation; however, the consequences of the maladaptive effects of pulmonary vasoconstriction represent formidable therapeutic challenges. Understanding the basic mechanisms of hypoxic pulmonary vasoconstriction will enhance the assimilation of translational research into clinical practice. The purposes of this review are to (1) define basic mechanisms of pulmonary vasoconstriction and vasorelaxation; (2) delineate the biphasic contractile response to hypoxia; (3) critically examine data that support the mediator hypothesis versus the ion channel hypothesis; and (4) explore potential mechanistic-based therapies for hypoxic pulmonary vasoconstriction. ER - TY - JOUR T1 - Operation Everest II: elevated high-altitude pulmonary resistance unresponsive to oxygen. A1 - Groves, B M A1 - Reeves, J T A1 - Sutton, J R A1 - Wagner, P D A1 - Cymerman, a A1 - Malconian, M K A1 - Rock, P B A1 - Young, P M A1 - Houston, C S Y1 - 1987/// JF - Journal of applied physiology (Bethesda, Md. : 1985) VL - 63 IS - 2 SP - 521 EP - 530 SN - 8750-7587 (Print) DO - 10.1093/bja/aep290 N2 - High altitude increases pulmonary arterial pressure (PAP), but no measurements have been made in humans above 4,500 m. Eight male athletic volunteers were decompressed in a hypobaric chamber for 40 days to a barometric pressure (PB) of 240 Torr, equivalent to the summit of Mt. Everest. Serial hemodynamic measurements were made at PB 760 (sea level), 347 (6,100 m), and 282/240 Torr (7,620/8,840 m). Resting PAP and pulmonary vascular resistance (PVR) increased from sea level to maximal values at PB 282 Torr from 15 +/- 0.9 to 34 +/- 3.0 mmHg and from 1.2 +/- 0.1 to 4.3 +/- 0.3 mmHg.l-1 X min, respectively. During near maximal exercise PAP increased from 33 +/- 1 mmHg at sea level to 54 +/- 2 mmHg at PB 282 Torr. Right atrial and wedge pressures were not increased with altitude. Acute 100% O2 breathing lowered cardiac output and PAP but not PVR. Systemic arterial pressure and resistance did not rise with altitude but did increase with O2 breathing, indicating systemic control differed from the lung circulation. We concluded that severe chronic hypoxia caused elevated pulmonary resistance not accompanied by right heart failure nor immediately reversed by O2 breathing. ER - TY - JOUR T1 - Do changes of 6-minute walk distance predict clinical events in patients with pulmonary arterial hypertension?: A meta-analysis of 22 randomized trials A1 - Savarese, Gianluigi A1 - Paolillo, Stefania A1 - Costanzo, Pierluigi A1 - D'Amore, Carmen A1 - Cecere, Milena A1 - Losco, Teresa A1 - Musella, Francesca A1 - Gargiulo, Paola A1 - Marciano, Caterina A1 - Perrone-Filardi, Pasquale Y1 - 2012/// PB - Elsevier Inc. JF - Journal of the American College of Cardiology VL - 60 IS - 13 SP - 1192 EP - 1201 SN - 1558-3597 (Electronic)\r0735-1097 (Linking) DO - 10.1016/j.jacc.2012.01.083 N2 - Objectives: The objectives of this study were to verify whether improvement in 6-min walk distance (6MWD) is associated with clinical outcome in pulmonary arterial hypertension (PAH). Background: 6MWD is used as an endpoint to assess the benefit of therapies in PAH. However, whether changes in 6MWD correlate with clinical outcome is unknown. Methods: Randomized trials assessing 6MWD in patients with PAH and reporting clinical endpoints were included in a meta-analysis. The meta-analysis was performed to assess the influence of treatment on outcomes. Meta-regression analysis was performed to test the relationship between 6MWD changes and outcomes. Results: Twenty-two trials enrolling 3,112 participants were included. Active treatments led to significant reduction of all-cause death (odds ratio [OR]: 0.429; 95% confidence interval [CI]: 0.277 to 0.664; p < 0.01), hospitalization for PAH, and/or lung or heart-lung transplantation (OR: 0.442; 95% CI: 0.309 to 0.632; p < 0.01), initiation of PAH rescue therapy (OR: 0.555; 95% CI: 0.347 to 0.889; p = 0.01), and composite outcome (OR: 0.400; 95% CI: 0.313 to 0.510; p < 0.01). No relationship between 6MWD changes and outcomes was detected. Conclusions: In patients with PAH, improvement in 6MWD does not reflect benefit in clinical outcomes. © 2012 American College of Cardiology Foundation. ER - TY - JOUR T1 - Pathogenesis of High-Altitude Pulmonary Edema A1 - Swenson, Erik R A1 - Maggiorini, Marco A1 - Mongovin, Stephen A1 - Gibbs, J Simon R A1 - Greve, Ilona A1 - Mairbaurl, Heimo A1 - Bartsch, Peter Y1 - 2002/// JF - Jama VL - 287 IS - 17 SP - 2228 EP - 2235 ER - TY - JOUR T1 - Interpretación de los gases arteriales en Bogotá Una propuesta para facilitar y unificar la lectura Interpretation of arterial blood gases in Bogota ( 2640 meters above sea level ) based on the Siggaard- Andersen nomogram A proposal for simplifying and un A1 - Lasso, Javier Iván Y1 - 2014/// JF - Revista Colombiana de Neumología VL - 26 IS - 1 SP - 25 EP - 36 ER - TY - JOUR T1 - Effects of high altitude exposure on the pulmonary circulation A1 - Penaloza, Dante Y1 - 2012/// JF - Revista Española Cardiologia VL - 65 IS - 12 SP - 1075 EP - 1078 DO - 10.1016/j.rec.2012.06.017 N2 - Historia del artı´culo: On-line el 12 de octubre de 2012 Má s de 140 millones de personas habitan sobre los 2.500 m de altura. En la regió n andina existe la mayor densidad de població n sobre los 3.500 m. Por otro lado, es creciente el nú mero de personas que habitan a nivel del mar (NM) y se movilizan a alturas mediana, grande o extrema por razones laborales o científicas, por turismo o por deporte, como ocurre con excursionistas, montañ istas y esquiadores. Por ello es de interé s conocer los efectos de la altura en aspectos fisioló gicos y estructurales del organismo humano. Los efectos de la altura se deben a la baja presió n baromé trica y, por lo tanto, a una reducció n en la presió n parcial de oxígeno en el aire inspirado. Esta condició n de hipoxia hipobá rica es la causa de la hipoxia alveolar e hipoxemia en los seres humanos que habitan o ascienden a la altura. Mú ltiples son las respuestas al estímulo hipó xico, así como los mecanismos adaptativos. En ocasiones, hay mala adaptació n en quien asciende a la altura. En otras, hay pé rdida de la adaptació n en el nativo de altura. En este artículo editorial se revisan resumidamente los efectos de la altura en la circulació n pulmonar en tres situaciones: hipoxia cró nica, hipoxia aguda e hipoxia subaguda. HIPOXIA CR NICA Nativo normal de grandes alturas Estudios pioneros de investigadores peruanos demostraron con cateterismo cardiaco la presencia de hipertensió n pulmonar (HP) asintomá tica en nativos sanos residentes en una comunidad andina ubicada a 4.540 m de altura 1 . Posteriores investigaciones a diferentes alturas en los Andes y en Asia permitieron establecer que la relació n entre la altitud y la presió n arterial pulmonar media (PAPm) está representada por una curva de tipo parabó lico, de forma tal que por encima de los 3.500 m hay HP leve a moderada asociada con niveles adaptativos de hipoxemia y policitemia. En nuestro estudio, a 4.540 m (presió n baromé trica, 445 mmHg; presió n parcial de oxígeno en el aire inspirado, 80 mmHg), la PAPm fue 28 mmHg, con saturació n arterial de oxígeno (SaO 2) del 80% y hemoglobina en 20 g/dl 1 . En nativos que viven a esta altitud fallecidos en accidente, el estudio histoló gico cuantitativo de las arterias pulmonares demostró engrosamiento de la capa media de cé lulas musculares lisas (CML) en las pequeñ as arterias distales, con extensió n de la capa muscular hasta las arteriolas ER - TY - JOUR T1 - Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: Results from the pulmonary hypertension registry of the United Kingdom and Ireland A1 - Ling, Yi A1 - Johnson, Martin K. A1 - Kiely, David G. A1 - Condliffe, Robin A1 - Elliot, Charlie A. A1 - Gibbs, J. Simon R A1 - Howard, Luke S. A1 - Pepke-Zaba, Joanna A1 - Sheares, Karen K K A1 - Corris, Paul A. A1 - Fisher, Andrew J. A1 - Lordan, James L. A1 - Gaine, Sean A1 - Coghlan, J. Gerry A1 - Wort, S. John A1 - Gatzoulis, Michael A. A1 - Peacock, Andrew J. Y1 - 2012/// JF - American Journal of Respiratory and Critical Care Medicine VL - 186 IS - 8 SP - 790 EP - 796 SN - 1073-449X DO - 10.1164/rccm.201203-0383OC N2 - Rationale: Incident pulmonary arterial hypertension was underrepresented in most pulmonary hypertension registries and may have a different disease profile to prevalent disease.Objectives: To determine the characteristics and outcome of a purely incident, treatment-naive cohort of idiopathic, heritable, and anorexigen-associated pulmonary arterial hypertension and to determine the changes in presentations and survival over the past decade in the United Kingdom and Ireland.Methods: All consecutive newly diagnosed patients from 2001 to 2009 were identified prospectively.Measurements and Main Results: A total of 482 patients (93% idiopathic, 5% heritable, and 2% anorexigen-associated pulmonary arterial hypertension) were diagnosed, giving rise to an estimated incidence of 1.1 cases per million per year and prevalence of 6.6 cases per million in 2009. Younger patients (age ≤ 50 yrs) had shorter duration of symptoms, fewer comorbidities, better functional and exercise capacity, higher percent diffusing capacit... ER - TY - JOUR T1 - 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension A1 - Galiè, Nazzareno A1 - Humbert, Marc A1 - Vachiery, Jean-Luc A1 - Gibbs, Simon A1 - Lang, Irene A1 - Torbicki, Adam A1 - Simonneau, Gérald A1 - Peacock, Andrew A1 - Vonk Noordegraaf, Anton A1 - Beghetti, Maurice A1 - Ghofrani, Ardeschir A1 - Gomez Sanchez, Miguel Angel A1 - Hansmann, Georg A1 - Klepetko, Walter A1 - Lancellotti, Patrizio A1 - Matucci, Marco A1 - McDonagh, Theresa A1 - Pierard, Luc A. A1 - Trindade, Pedro T. A1 - Zompatori, Maurizio A1 - Hoeper, Marius Y1 - 2016/// JF - European Heart Journal VL - 37 IS - 1 SP - 67 EP - 119 SN - 1522-9645 DO - 10.1093/eurheartj/ehv317 N2 - ALAT : alanine aminotransferase ASAT : aspartate aminotransferase APAH : associated pulmonary arterial hypertension BAS : balloon atrial septostomy BMPR2 : bone morphogenetic protein receptor 2 BNP : brain natriuretic peptide BPA : balloon pulmonary angioplasty BREATHE : Bosentan Randomised trial of Endothelin Antagonist THErapy CAV1 : caveolin-1 CCB : calcium channel blocker cGMP : cyclic guanosine monophosphate CHD : congenital heart disease CI : cardiac index CMR : cardiac magnetic resonance CO : cardiac output COPD : chronic obstructive pulmonary disease Cpc-PH : combined post-capillary and pre-capillary pulmonary hypertension CPET : cardiopulmonary exercise testing CPFE : combined pulmonary fibrosis and emphysema CT : computed tomography CTD : connective tissue disease CTPA : computed tomography pulmonary angiogram CTEPH : chronic thromboembolic pulmonary hypertension DLCO : diffusing capacity of the lung for carbon monoxide DPAH : drug-induced pulmonary arterial hypertension DPG : diastolic pressure gradient (diastolic PAP − mean PAWP) EACVI : European association of cardiovascular imaging ECG : electrocardiogram ECMO : extracorporeal membrane oxygenation EIF2AK4 : eukaryotic translation initiation factor 2 alpha kinase 4 EMA : European Medicines Agency ERA : endothelin receptor antagonist FC : functional class FDA : US Food and Drug Administration HAART : highly active antiretroviral therapy HIV : human immunodeficiency virus HF-pEF : heart failure with preserved left ventricular ejection fraction HPAH : heritable pulmonary arterial hypertension HRCT : high resolution computed tomography ICU : intensive care unit INR : international normalized ratio IPAH : idiopathic pulmonary arterial hypertension Ipc-PH : isolated post-capillary pulmonary hypertension IPF : idiopathic pulmonary fibrosis i.v. : intravenous IVC : inferior vena cava LA : left atrium/atrial LHD : left heart disease LV : left ventricle/ventricular MR : magnetic resonance NYHA : New York Heart Association NO : nitric oxide NT-proBNP : N-terminal pro-brain natriuretic peptide PA : pulmonary artery PaCO2 : arterial carbon dioxide pressure PaO2 : arterial oxygen pressure PAH : pulmonary arterial hypertension PAP : pulmonary arterial pressure PAPm : mean pulmonary arterial pressure PAPs : systolic pulmonary arterial pressure PAWP : pulmonary artery wedge pressure PASP : pulmonary artery systolic pressure PCH : pulmonary capillary haemangiomatosis PDE-5i : phosphodiesterase type 5 inhibit… ER - TY - JOUR T1 - Reference Values For Arterial Blood Gases At An Altitude Of 2640 Meters A1 - Maldonado, Dario. Gonzalez, M. Barrero, M. Y1 - 2013/// JF - C76. Exercise, Hypoxia, and Altitude SP - A4852 EP - A4852 SN - 1073-449X DO - doi:10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A4852 N2 - RATIONALE: There is an inverse relationship between altitude, barometric and oxygen pressures: at higher altitudes lower barometric, inspired and arterial (PaO2) pressures. This stimulates the respiratory centers to increase alveolar ventilation decreasing PaCO2 and HCO3. The purpose of if this study was to establish normal values for arterial blood gases (ABG) in Bogota, a city located at high altitude: 2640 m. METHODS: Cross sectional study done in healthy non-smoking, non-obese adults, >18 years, male and female, with a normal spirometry, who born above 2000 meters and had lived more than 10 years in Bogota. The presence of acute alveolar hyperventilation during the arterial puncture was ruled out by minute ventilation and respiratory exchange ratio measurement. Analysis of group differences was tested using unpaired t test and ANOVA. The correlations between age, PaO2 and PaCO2 were calculated. RESULTS: We included 374 healthy adults, 18 to 83 years old, 55% women. There were not differences by gender or age in the pH (7,43 +/-,02). There were a decrease of the PaO2 and SaO2 and an increase of the P(A-a)O2 and PaCO2 as the age increased (P<0.001) (Table 1, figures 1 and 2). In comparison with males, the PaO2 was significantly lower in women 50 to 69 years old and the PaCO2 significantly lower in women 18 to 39 years old. The correlations between the increase in age, the decrease in PaO2 and the increase in PaCO2 were larger in women than in men (Table 2). CONCLUSIONS: This study of a representative sample of healthy subjects of both genders establishes the reference values for arterial blood gases in Bogota, a city located at high altitude (2640 m). As expected, the PaO2 and PaCO2 were significantly lower than the normal values at sea level. The PaO2 decreased and the PaCO2 increased with age, particularly in women after 50 years old. We postulate that the lower PaCO2 seen in young women can be explained by higher alveolar ventilation related with hormonal activity which decreases with increasing age. (Table Presented). ER - TY - JOUR T1 - Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. A1 - D'Alonzo, G E A1 - Barst, R J A1 - Ayres, S M A1 - Bergofsky, E H A1 - Brundage, B H A1 - Detre, K M A1 - Fishman, a P A1 - Goldring, R M A1 - Groves, B M A1 - Kernis, J T Y1 - 1991/// JF - Annals of internal medicine VL - 115 IS - 5 SP - 343 EP - 349 SN - 0003-4819 DO - 10.1059/0003-4819-115-5-343 N2 - OBJECTIVE: To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival. DESIGN: Registry with prospective follow-up. SETTING: Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart, Lung, and Blood Institute. PATIENTS: Patients (194) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988. MEASUREMENTS: At diagnosis, measurements of hemodynamic variables, pulmonary function, and gas exchange variables were taken in addition to information on demographic variables, medical history, and life-style. Patients were followed for survival at 6-month intervals. MAIN RESULTS: The estimated median survival of these patients was 2.8 years (95% Cl, 1.9 to 3.7 years). Estimated single-year survival rates were as follows: at 1 year, 68% (Cl, 61% to 75%); at 3 years, 48% (Cl, 41% to 55%); and at 5 years, 34% (Cl, 24% to 44%). Variables associated with poor survival included a New York Heart Association (NYHA) functional class of III or IV, presence of Raynaud phenomenon, elevated mean right atrial pressure, elevated mean pulmonary artery pressure, decreased cardiac index, and decreased diffusing capacity for carbon monoxide (DLCO). Drug therapy at entry or discharge was not associated with survival duration. CONCLUSIONS: Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index. Such an equation, once validated prospectively, could be used as an adjunct in planning treatment strategies and allocating medical resources. ER - TY - JOUR T1 - Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders. A1 - Hoit, Brian D A1 - Dalton, Nancy D A1 - Erzurum, Serpil C A1 - Laskowski, Daniel A1 - Strohl, Kingman P A1 - Beall, Cynthia M Y1 - 2005/// JF - Journal of applied physiology (Bethesda, Md. : 1985) VL - 99 IS - 5 SP - 1796 EP - 1801 SN - 8750-7587 (Print)\r0161-7567 (Linking) DO - 10.1152/japplphysiol.00205.2005 N2 - When O2 availability is reduced unavoidably, as it is at high altitude, a potential mechanism to improve O2 delivery to tissues is an increase in blood flow. Nitric oxide (NO) regulates blood vessel diameter and can influence blood flow. This field study of intrapopulation variation at high altitude tested the hypothesis that the level of exhaled NO (a summary measure of pulmonary synthesis, consumption, and transfer from cells in the airway) is directly proportional to pulmonary, and thus systemic, blood flow. Twenty Tibetan male and 37 female healthy, nonsmoking, native residents at 4,200 m (13,900 ft), with an average O2 saturation of hemoglobin of 85%, participated in the study. The geometric mean partial pressure of NO exhaled at a flow of 17 ml/s was 23.4 nmHg, significantly lower than that of a sea-level reference group. However, the rate of NO transfer out of the airway wall was seven times higher than at sea level, which implied the potential for vasodilation of the pulmonary blood vessels. Mean pulmonary blood flow (measured by cardiac index) was 2.7 +/- 0.1 (SE) l/min, and mean pulmonary artery systolic pressure was 31.4 +/- 0.9 (SE) mmHg. Higher exhaled NO was associated with higher pulmonary blood flow; yet there was no associated increase in pulmonary artery systolic pressure. The results suggest that NO in the lung may play a key beneficial role in allowing Tibetans at 4,200 m to compensate for ambient hypoxia with higher pulmonary blood flow and O2 delivery without the consequences of higher pulmonary arterial pressure. ER - TY - JOUR T1 - Sabiston and Spencer’s Surgery of the Chest, 8th Edition A1 - Ballian, Nikiforos A1 - Weigel, Tracey L. Y1 - 2011/// PB - Elsevier Inc. JF - Journal of Surgical Research VL - 167 IS - 2 SP - 206 EP - 206 DO - 10.1016/j.jss.2010.11.912 N2 - Through seven successful editions, Sabiston & Spencer Surgery of the Chest has set the standard in cardiothoracic surgery references. Now, the new 8th Edition, edited by Frank W. Sellke, MD, Pedro J. del Nido, MD, and Scott J. Swanson, MD, carries on this tradition with updated coverage of today's essential clinical knowledge from leaders worldwide. Guidance divided into three major sections-Adult Cardiac Surgery, Congenital Heart Surgery, and Thoracic Surgery-lets you quickly find what you need, while new and revised chapters reflect all of the important changes within this rapidly evolving specialty. Expert Consult functionality-new to this edition-enables you to access the complete contents of the 2-volume set from anyplace with an Internet connection for convenient consultation where and when you need it. This is an ideal source for mastering all of the most important current knowledge and techniques in cardiac and thoracic surgery-whether for specialty board review or day-to-day practice.Features short, focused chapters that help you find exactly what you need.Presents the work of international contributors who offer a global view of the entire specialty.Covers thoracic surgery as well as adult and pediatric cardiac surgery for a practical and powerful single source. Includes nearly 1,100 illustrations that help to clarify key concepts. Features online access to the complete contents of the 2-volume text at expertconsult.com for convenient anytime, anywhere reference.Covers the hottest topics shaping today's practice, including the latest theory and surgical techniques for mitral valve disease, advances in the treatment of congenital heart disease, minimally invasive surgical approaches to the treatment of adult and congenital cardiac disease and thoracic disease, stent grafting for aortic disease, and cell-based therapies. Your purchase entitles you to access the web site until the next edition is published, or until the current edition is no longer offered for sale by Elsevier, whichever occurs first. Elsevier reserves the right to offer a suitable replacement product (such as a downloadable or CD-ROM-based electronic version) should access to the web site be discontinued. ER - TY - JOUR T1 - High Altitude Medicine and Physiology A1 - Luks, A. M., Milledge, J. S., West, J. B., Schoene, R. B. Y1 - 2012/// JF - Postgraduate medical journal VL - 5 ED IS - 770 SP - 961 EP - 961 SN - 0340913444, 9780340913444 DO - 10.1136/bjsm.35.6.451-b N2 - A comprehensive update this preeminent and accessible text, this fifth edition of a bestseller was developed as a response to man's attempts to climb unaided to higher altitudes and to spend more time in these conditions for both work and recreation. It describes the ever-expanding challenges that doctors face in dealing with the changes in human physiology and particular medical conditions that arise from exposure to altitude and cold.The highly respected authors of this fifth edition are internationally recognised for their academic research in the field, and are all experienced mountaineering physicians who have dealt with illness and accidents in high places. They have continued to provide a text that will help physicians to improve the health and safety of all people who visit, live, or work in cold and thin air conditions experienced in high mountains.High Altitude Medicine and Physiology is invaluable reading for any doctor accompanying an expedition or advising patients on a visit to altitude, physicians specialising in illness and accidents in high places, and for physiologists who study our dependence on oxygen and the adaptation of the body to altitude. ER - TY - JOUR T1 - Predicting outcomes in pulmonary arterial hypertension based on the 6-minute walk distance A1 - Farber, Harrison W. A1 - Miller, Dave P. A1 - McGoon, Michael D. A1 - Frost, Adaani E. A1 - Benton, Wade W. A1 - Benza, Raymond L. Y1 - 2015/// PB - Elsevier JF - Journal of Heart and Lung Transplantation VL - 34 IS - 3 SP - 362 EP - 368 SN - doi:10.1016/j.healun.2014.08.020 DO - 10.1016/j.healun.2014.08.020 N2 - Background Clinical studies of pulmonary arterial hypertension have used the change in the 6-minute walk distance (6MWD) as a clinical end point; however, its association with survival outcomes has not been well established. In this analysis, we examined the prognostic value of the baseline 6MWD, absolute thresholds of the 6MWD, and change in the 6MWD. Methods Patients in the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) with 6MWD at enrollment, with or without a follow-up assessment within the first year of observation, were included. Kaplan-Meier survival estimates were computed for sub-sets with baseline 6MWD results that were above or below all possible thresholds and for sub-sets with a change in the 6MWD that was 10 percentage points above or below all possible thresholds, including improvement thresholds and worsening thresholds. Multivariable Cox regression models assessed the effect of improvement and worsening in the 6MWD on 1-year survival, adjusted for baseline factors. Results One-year survival estimates were higher for patients with a baseline 6MWD above vs below a threshold, although no specific threshold was more prognostic than another. In a model adjusted for the baseline 6MWD and risk score, worsening of the 6MWD over time significantly predicted decreased survival, but improvement in the 6MWD did not affect survival. Conclusions No 6MWD improvement threshold carries particular prognostic value. Improvement in the 6MWD was not associated with survival, but worsening of the 6MWD was strongly and significantly associated with poor prognosis. ER - TY - JOUR T1 - Determinación de los costos directos e indirectos en hipertensión pulmonar en Colombia A1 - Londoño D, Villaquirán C, Dueñas R, Gómez E, Coral P. Y1 - 2013/// JF - Revista Colombiana de Neumología VL - 25 IS - 3 SP - 145 EP - 156 N2 - INTRODUCTION: pulmonary arterial hypertension is an uncommon condition, whose mor- bidity and mortality are high. Its diagnosis is highly specialized and very costly. The same holds true for its treatment, follow-up, absences from work, and hospitalizations for its cause. In Colom- bia, the costs associated with the diagnosis and treatment of this condition, which are essential for many healthcare planning processes, are unknown. METHODS: Direct costs: the diagnostic algorithm for pulmonary arterial hypertension of the European Respiratory Society (ERS) was applied to an hypothetic cohort of one hundred patients with pulmonary hypertension. A value was assigned to each procedure in accordance with the national tariff manual. Diagnosis was divided into an initial phase, focusing on ruling out groups I, II, IV of pulmonary hyperten- sion, and a second phase, focusing on hemodynamic diagnosis, exercise capabiltiy, and type. A delphi panel indicated therapy according to the functional class, the follow-up procedures, and their frequency. Indirect costs: these were established by interviewing 35 patients with pulmonary arterial hypertension about lost working days and disabilities. Total costs are equal to the sum of direct and indirect costs. All costs are presented in US dollars (1 US dollar = 1.900 Colombian pesos for the year 2010). RESULTS: Direct costs: during the first phase of diagnosis, an investment of US $23,874.90 was done for 100 patients, which repre- sents an investment of US $238,749 per patient. For the second phase, the investment is close to US $14,854.57, corresponding to $742,7 per patient. In patients with functional classes II and III, the total cost for 100 patients is US $9,128,933.46, both for inpatients and outpa- tients. In functional class IV patients, the total cost of managing 100 individuals is US $35,128,260.2, which represents an average cost of US $351,282.6 per patient. Costs are increased by 384,6% in class IV patients in comparison with class II-III patients. Indirect costs: 31% of surveyed patients had to take leaves from work during the last year (an average of 58 days), and 28,6% required hospitalization. Taking into account that the minimum legal monthly salary in Colombia is US $279, the average monthly income of surveyed patients was US $804 (daily income of US $26,8). The cost of absences from work of the eleven subjects was US $17,098.4. Since insurance companies in Colombia cover only 70% of income from salaries… ER - TY - JOUR T1 - Six-minute walk test in pulmonary arterial hypertension. A1 - Demir, Rengin A1 - Kucukoglu, Mehmet Serdar Y1 - 2015/// JF - Anatolian journal of cardiology VL - 15 IS - 3 SP - 249 EP - 254 SN - 2149-2263 DO - 10.5152/akd.2015.5834 N2 - Exercise intolerance is the main characteristic of pulmonary arterial hypertension (PAH). The six-minute walk test (6MWT) and cardiopulmonary exercise test are widely used in assessing exercise capacity of PAH patients. Six-minute walk distance (6MWD) has been specified as the main clinical outcome in PAH and has been used as the primary end-point in many studies conducted for new PAH treatments. Using 6MWD as the end-point in clinical studies has many advantages. 6MWT is an inexpensive, easily applicable, and repeatable standardized test that is well-tolerated by PAH patients. Moreover, it is a valid measure of symptomatic improvement. It is correlated with variables of maximal cardiopulmonary exercise test as a measure of submaximal exercise capacity and disease severity markers such as functional class and pulmonary hemodynamics. It is widely used in clinical practice together with other invasive and non-invasive disease markers in assessing disease progression and response to treatment. In addition, it has prognostic importance and is a good prognostic marker. On the other hand, there are limitations to the use of 6MWD as the primary end-point in PAH treatment. It has decreased sensitivity in individuals with less severe disease and high 6MWD at baseline and decreased adequacy in assessing the effects of treatment in patients who are still under PAH treatment. Despite the limitations, 6MWD plays a key role in the evaluation and management of PAH patients. ER - TY - JOUR T1 - The 6MWT as a prognostic tool in pulmonary arterial hypertension: results from the COMPERA registry A1 - Zelniker, Thomas A. A1 - Huscher, Dörte A1 - Vonk-Noordegraaf, Anton A1 - Ewert, Ralf A1 - Lange, Tobias J. A1 - Klose, Hans A1 - Dumitrescu, Daniel A1 - Halank, Michael A1 - Held, Matthis A1 - Gall, Henning A1 - Pittrow, David A1 - Hoeper, Marius M. A1 - Frankenstein, Lutz Y1 - 2018/// KW - 6-Minute walk test KW - Cut-off value KW - PAH KW - Pulmonary arterial hypertension KW - Risk stratification PB - Springer Berlin Heidelberg JF - Clinical Research in Cardiology VL - 107 IS - 6 SP - 460 EP - 470 SN - 0039201812075 DO - 10.1007/s00392-018-1207-5 UR - http://dx.doi.org/10.1007/s00392-018-1207-5 L1 - file:///C:/Users/fandinoc/OneDrive - Merck Sharp & Dohme, Corp/PERSONAL/PERSONAL/TESIS/Caminata Compera 2018.pdf N2 - Background: In patients with pulmonary arterial hypertension, the 6-Minute Walk Test (6MWT) is recommended for risk stratification and follow-up by all guidelines. However, the prognostic value of the 6MWT has been discussed controversially. We sought to compare and validate all published 6MWT cut-off points. Methods: From the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA)—registry we identified 2391 patients with pulmonary arterial hypertension who had at least one documented 6MWT measurement. A Medline search identified a total of 21 different threshold values for either single-point or change of 6MWT. All values were tested individually for prognostication of 1-year, 2-year and 3-year all-cause mortality. Results: The highest positive likelihood ratio was a cut-off value < 165 ms, whereas the best negative likelihood ratio was found to be a threshold of 440 ms. Furthermore, improvement in 6MWT had considerably less predictive value on mortality and survival than deterioration. Moreover, absolute single-point values outperformed change values for both improvement and worsening. Conclusion: Our data confirmed the prognostic relevance of the 6MWT and support the cut-off values stated in most recent guidelines. Furthermore, these results explain why changes in 6MWT did not correlate consistently with prognosis in previous studies. ER - TY - JOUR T1 - Pulmonary Pressure, Cardiac Output, and Arterial Oxygen Saturation during Exercise at High Altitude and at Sea Level A1 - Banchero, N. A1 - Sime, F. A1 - Penaloza, D. A1 - Cruz, J. A1 - Gamboa, R. A1 - Marticorena, E. Y1 - 1966/// JF - Circulation VL - 33 IS - 2 SP - 249 EP - 262 DO - 10.1161/01.CIR.33.2.249 N2 - The response elicited by exercise on pulmonary pressure, cardiac output, and arterial oxygen saturation in 35 lifetime residents of high altitude has been studied at high altitude (14,900 feet above sea level), and 22 residents of low altitude have been studied at sea level. A procedure combining cardiac catheterization, arterial cannulation, and spirometry was carried out. The exercise was moderate and was performed in supine position using a bicycle ergometer, the work load being 300 kg-m/min/m,2 and the average increase of the oxygen uptake being 4.7 times at sea level and 4.8 times at high altitude.Both at sea level and at high altitude the cardiac output augmented during exercise proportionally to the increase in oxygen uptake, and thus followed the pattern of response described by other authors. The cardiac output as well as the oxygen intake, for the magnitude of exertion performed in this study, was almost the same at sea level and at high altitude. The cardiac output rose during exercise almost exclusively as a result of an increase in the heart rate, with the stroke volume remaining practically constant.Despite similar increase in cardiac output, the response of pulmonary pressure was smaller for sea-level subjects than for the high-altitude subjects. Increments of mean pulmonary pressure of nearly 50% and 100% were observed on exercise at sea level and at high altitude, respectively.During exercise the arterial oxygen saturation did not change in the sea-level studies, but decreased significantly in the high-altitude studies. The decrement observed in high-altitude residents is related to a fall in arterial pO2 which at resting conditions is placed on the steep part of the oxygen dissociation curve. ER - TY - JOUR T1 - A contemporary approach to pulmonary arterial hypertension A1 - Krishnan, Udhay A1 - Horn, Evelyn M. Y1 - 2016/// PB - Current Atherosclerosis Reports JF - Current Atherosclerosis Reports VL - 18 IS - 9 SP - 1 EP - 8 DO - 10.1007/s11883-016-0608-z N2 - In recent years, there have been major changes in the landscape of pulmonary arterial hypertension therapy with the introduction of novel agents and innovative treatment strategies for this progressive disease. The aim of this review is to discuss the evolution in trial design in this field and highlight the salient features of recently published studies. We also summarize our approach to therapy selection in this chronic disease and identify areas for future exploration. The therapeutic armamentarium now includes 13 approved therapies. While most of these agents have been studied in small, short-term trials using the 6-min walk distance as a primary endpoint, there has been a shift in recent years toward larger, long-term, event-driven trials that utilize combined morbidity and mortality endpoints. The SERAPHIN and GRIPHON trials were two such studies, which led to the approval of the dual endothelin-receptor antagonist macitentan and the selective prostacyclin receptor antagonist selexipag, respectively. Other event-driven trials, like AMBITION and COMPASS-2, have provided valuable insight into the use of combined oral therapies in symptomatic patients. In conclusion, despite being a more manageable disease in the modern treatment era, pulmonary hypertension is still associated with considerable morbidity and much more work remains to be done in this field. Important questions remain about the most optimal way to manage patients and conduct trials going forward. ER - TY - GEN T1 - Psychophysical bases of perceived exertion A1 - A.V, Borg Gunnar Y1 - 1982/// PB - Medicine and Science in sports and exercise L1 - file:///C:/Users/fandinoc/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Unknown - Unknown - Psychophysical_bases_of_perceived_exertion.12.pdf.pdf ER - TY - JOUR T1 - Pulmonary arterial hypertension: Epidemiology and registries A1 - McGoon, Michael D. A1 - Benza, Raymond L. A1 - Escribano-Subias, Pilar A1 - Jiang, Xin A1 - Miller, Dave P. A1 - Peacock, Andrew J. A1 - Pepke-Zaba, Joanna A1 - Pulido, Tomas A1 - Rich, Stuart A1 - Rosenkranz, Stephan A1 - Suissa, Samy A1 - Humbert, Marc Y1 - 2013/// KW - databases KW - epidemiology KW - pulmonary hypertension KW - registries JF - Journal of the American College of Cardiology VL - 62 IS - 25 SUPPL. DO - 10.1016/j.jacc.2013.10.023 L1 - file:///C:/Users/fandinoc/OneDrive - Merck Sharp & Dohme, Corp/PERSONAL/PERSONAL/TESIS/BOBLIOGRAFIA ADICIONAL/Pulmonary arterial hypertensionepidemiology and registries.pdf N2 - Registries of patients with pulmonary arterial hypertension (PAH) have been instrumental in characterizing the presentation and natural history of the disease and provide a basis for prognostication. Since the initial accumulation of data conducted in the 1980s, subsequent registry databases have yielded information about the demographic factors, treatment, and survival of patients and have permitted comparisons between populations in different eras and environments. Inclusion of patients with all subtypes of PAH has also allowed comparisons of these subpopulations. We describe herein the basic methodology by which PAH registries have been conducted, review key insights provided by registries, summarize issues related to interpretation and comparison of the results, and discuss the utility of data to predict survival outcomes. Potential sources of bias, particularly related to the inclusion of incident and/or prevalent patients and missing data, are addressed. A fundamental observation of current registries is that survival in the modern treatment era has improved compared with that observed previously and that outcomes among PAH subpopulations vary substantially. Continuing systematic clinical surveillance of PAH will be important as treatment evolves and as understanding of mechanisms advance. Considerations for future directions of registry studies include enrollment of a broader population of patients with pulmonary hypertension of all clinical types and severity and continued globalization and collaboration of registry databases. © 2013 by the American College of Cardiology Foundation. Published by Elsevier Inc. ER -