Him ORIGINAL CONTRIBUTION Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness The ESCAPE Trial _DVANCES IN MEDICAL THERAPY have improved outcomes for many ambulatory patients with heart failure and low jection fraction (EP). However, each year an estimated 250000 to 300.000 patients are hospital ure with low EF? and the vival rate after hospitalization may be as low as 50%, even with recom- mended medical therapies.” In nonrandomized studies, patients undergoing therapy with vasodilators and diuretics to reduce filling pres- sures to near normal levels have had acute and sustained improvements in hemodynamics, mitral regurgitation, and exercise tolerance." Without a randomized study of hemodynamic monitoring with the pulmonary ar~ tery catheter (PAC), however, it could, not be determined whether PACs im- proved outcomes in addition to other components of intensive heatt failure management There is considerable controversy for heat fal- lover tse of the PAC in critical illness. The Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) trial demon- strated higher mortality for patients thought to require PAC during hospi- talization, although without excess risk for patients with heatt failure."® Re- ports from acute myocardial infarc See also pp 1664 and 1693, (©2005 American Medical Asso Downloaded From: https: rn, All rights reserved, (Repinted) AMA, Ocber Eres ga ose ea 080 TN, pee wo Se siven pallies men Coane Boek ‘puthors are sted athe end of his article Division, Departmen of Melcine, 75 Franc Comtesponding Author Lynne Wi" Stevenson, MD, PBB? orton, MA 02715 (etevenson@parners Brigham and Women’s Hosptial, Cadovascuat 0. Mexico | Access Provided by JAMA User on 06/07/2023ESCAPE TRIAL OF PULMONARY ARTERY CATHETERIZATION EFFECTIVENESS tion populations further raised con- therapies The target patient was su ems that PACS increased mortality, ficiently ill with advanced heart fail- tnd moratorium on PAC use was pro- ure to make use of the PAC reason posed."” Recommendations from a able, butalso sulficiently stable to make Wworking group ofrepresentaives om crossover to PAG for urgent manage- the National Heart, Lung.and Blood In- ment unlikely. Severity prior toadmis- stitute (NHLBD, the Foodand Drug Ad- sion could be met by the following er- Talnisttation, and academic experts intra: (1) hosphualization for hear tahire cardiology, pulmonology, surgery, within the past year; (2) urgent visi vo nitaing, and criti eae led toa tril theemergency department or (3) teat dlesigned to test the PAC in patients ment during the preceding month with ‘with chronic heart failure. tnore than 160 mg of furasemide dally The complexity ofthis population (or equivalent), Random and the challenge of hemodynamic quired a least3 months of symptoms mmodynamic studies desirable. How- zyme (ACE) inhibitors and diuretics ever, refinement of clinical assess~_letventricular(LV) EF30% orles, sys" ment based on prior hemodynamic _tlicblood pressure 125mm Higor les investigation could diminish the im- and at last 1 sign and 1 symptom of pactof PAC information. Recognizing congestion. Exclusion criteria to mii this conflict, the decision was made mize confounding comorbidities o ur totestthe PAC with experienced heart gent crossover included creatinine evel fuilure investigators. For the Evalua- greater than 3.3 mg/dl (309.4 ymol/ tion Study of Congestive Heart Fail- 1), or prior use of dobutamine or do- ure and Pulmonary Atte Catheter- amine mote than 3 pgfkgfnin, or any ization Effectivencss (ESCAPE), the prior use of milrinone during the cur primary hypothesis was that for pa- tent hospitalization, Right heart cath- tients with severeheartniure, therapy cterization to assess pulmonary hyper- guided by PAC monitoring and clint~ tension during transplant evaluation falassessment would lead tomotedaya was permitted in patients receiving aliveand fewer days hospitalized dur therapy guided by clinical assessment ing 6 months compared with therapy alone if performed at the end of hos- aguded by clinical esseasinent alone. pltalization ee . P Aconcurrent PAC registry was ex- ‘METHODS tablished to characterize hospitalized Tial Organization patients receiving PACs considered vo ESCAPE wasan NHLBI-sponsoredran-_be required during heart failure man- domized wiel conducted at 26.experi- agement enced heart faire centersin the United Sines and Canada. The Brigham and Study Design and Analyses ‘Women's Hospital served as the clini- Patients were randomly assigned 1:1 10 caleoordinatingcenter,and Duke Clini- therapy guided by clinical assessment tal Research Institute was the data co- only (clinical asseasinent group) of ordinating center and performed all therapy guided by clinical assessment Statistical analyses. The NHLBI ap- and the PAC (PAC group). Random- pointedan independentdat and safery tation was staifid by ste using an- Tmonitoring board. Participating insti- dom block szesof2 or 4 through ce tutional review boards approved the tal telephone center. The treatment protocol, and written informed con- goal in the clinical assessment group sent was oblained from all patients, was resolution of elinical signs and . symptoms of congestion, particularly atients jugular venous pressure elevation, Inclusion criteria were designed to se- edema, and orthopnea, Treatment goals, lect patients with severe symptomatic in the PAC group were the same, with hheart failure despite recommended the addition of pulmonary capillary 1626 JAMA coher 5, 2005 Vo jamanetvrork.com by a Mexico | Access Provided by JAMA. User on 06/07/2023 wedge pressure (PCWP) of 15 mm Hg and right atrial pressure of mm Hg. Therapy was adjusted in both groups toavoid progressive renal dysfunction ‘or symptomatic systemic hypotension. The protocol did not specify drug: lection or dosing. Investigators were en- couraged to follow national guidelines for treatment of heart failure and to pri- marily use intravenous diuretics and va- sodilators, The use of inotropic agents for routine management was consis- tently and explicitly discouraged. No specific instructions were given regard- ing nesiritide, which beeame available during the course of the trial The Pulmonary Artery Catheter Education Project, a computer-based program created by the NHLBI, the Pood and Drug Administration, and the American College of Physicians, was used at study initiation to train Investigators and coordinators (hutp: ‘ow pacep org/asahq). Catheters were selected according to individual insti- tutional practice, Inthe PAC group, he modynamics were measured twice at baseline and at least twice daily the after, with pressure measurement from paper readings, A specific case report form listed anticipated PAC comphi- Patients were seen at 7 to 14 days, and 1, 2, 3, and 6 months after discharge Data were collected on clinical status, medications, exercise, and quality ofh measurements, Race and ethnicity were assessed by the study coordinator from patients and chart information to deter- tine degree of diverse representation in the study population. The primary end point, daysalive out of the hospital dur- ing 6 months following random tion, was analyzed using the Cox pro- portional hazards model. Component fend points included time to events. End points were calculated with patients re ceiving transplant or assist devices coded asdead, then recalculated coded asalive. Becatise patients and physicians were not blinded to treatment, physiologic secondary end points, focusing on mi- tral regurgitation (the subject of pend- ing analysis), natriuretic peptides, and peak oxygen consumption, were si 94, No. 1 Reprinted) (©2005 American Medical Association. All ights reserved.ESCAPE TRIAL OF PULMONARY ARTERY CATHETERIZATION EFFECTIVENESS lected as measurable without knowl achieving asignificant dillerence inthe = —= edge of group assignment, Other func- primary end point Figure 1+ CONSORT Dis Uional end points were G-minute walle The 2 randomized groups had simi- distance," the Minnesota Living with lar baseline characteristics (Taste 1), Heart Failure questionnaire, and the with 301 (00%) taking ACE inhibitors time trde-ol tol" which quantifies or angiotensin-receptor blockers, 268 [F#aapaioncr | [Fw macin ones hhow many months of life out of 24 (62%) taking B-blockers, and31(7%) | guecmecy., | | Ascineton| months patients would ade tofeelbet- with implantable defibrillators. Dur- | ‘agnernece | | 7" Se ter through a series of binay questions ingthe same me, patients rcetving the asked by a tained coordinator, as has PAC without randomization (PAC reg- ‘been described for moderate-severe heart istry) had higher LVEF, but more com- | #P3esFemisin ] [2 wanacn Pema failure. All baseline functional mea- promise of Blood pressure, xem so- | 7aggmmmenes | | ¢4etnreaeer sures were made before mndomization. dium and creatinine levels, and |suaommmes | | suxtmnioee ‘A new end point of time trade-off inotropic therapy (35% vs 15%). pom enced meee te adjusted survival was prospectively d fined for caplosatory apaheicas hein. Treatment After Randomization [Siyamunama] [Fv pamnaawe tegiated product ofthe daysaliveandthe Intravenous diuretics were sed in all |ang*t=tnmayn | |zortten mts proportion of months preferred incur- patients, Vasodilator therapy was used [tev atam| |" tear efor tent health at each time point in80 (57%) patents in the PAC group | ———________ Theoriginal design inclided 500ran-and-42 patents (10%) inthe cliniealas- CONOR da deg ie pogeofia 3 domizedpatent based onthesssump- sessment group (ota nesiniide, 66 Enger crate easement inal tion that the control group would have [15%]; nitroprusside, 50 [12%] nitro- 34 hepinary end pint. Sevekeen pats an ap expected 40 das dead or howpalpyetin, 16/46) Inaeoplethersy Senn ei Sane sn ized withan SD of30. The treated group was used in 9+ (4496) patients im the 10g imitations of placement and subsequent smsatsumed ohaveanexpectedum PAC groupand ee pate OO) inthe emer rns woman ote gaa erofdayvot52(08%40), Thisenlted clinical assessment group. Discharge patton bla doe in an estimated power of 84%, assum- prescriptions included ACE inhibitors’ #S*! ovonginal intention totret ing normaly of days hospitalized (as snglotensin-receptor blockers for 196 summinga2-sdedtestatana levelof-05). (01%) patients inthe PAC group andthe hospital (Fioune 2). The overall Interim unblinded analyses fr eificacy 195 patients (89%) in the clinical as- neutrality of the intervention was oceurredatter 19%, 40%, 59%, and67% sessment group, and blockers for 140. consistent across demographic sub- of the patients had been enrolled. (65%) patients in the PAC group and groups (Frcune 3). There were no “Approximate OBrien-Fleming bound 128 patients (59%) in the clinical as- significant differences in time to ates were used based on the group-sesstnent group. death or hospitalization, deaths, or SequentislmethodsofLanetal*Nopro- PACS were placed foradjusiment of days hospitalized (Taste 4). Both vision was made for stopping early for therapy in 198 (92%) patients in the groups had a median of 2.0 hospital- fuiliy. None ofthe tests were close PAC groupand 21 patients (10%) inthe zations per patient. Coding the 36 the stopping boundaries clinical assessment group during hos- patients who underwent cardiac The secondary end points, inclad- pitalization, PACs in patients in the transplantation or LV assist device ing exercise, natriuretic peptides, and treatment group werein pliceforame- placement as ether dead or alive did «quality of life, were analyzed with the dian of 1.9 days, during which all he not change the results test usingSAS version 82 (SAS Inst- modynamic parameters improved There were no clinical subgroups in tute Ine, Cary, NC) with ana level of (Taste 2)-Substanalimpactoftherapy which benefit or harm was shown, (05. All analyses were based on inten- on clinical goals by the time of disy There was a trend for beter PAC out- tion to treat charge was similar in both groups comes inthe centers with higher vol- tate 3). although average weight ume enrollment. There was no evi- RESULTS . loss was 3.2 kg for patients in the clini- dence of benefit or harm from the PAC Baseline Characteristics cal assessment group vs 40 kg for par in relation to intravenous vasoactive From January 18, 2000, to November tients inthe PAC group, serum creat therapy (TABLE 3) 17, 2003, 435 patients were enrolled nine level worsened less often in the (Froune 1). The data and safety moni- PAC group. Safety of the PAC toring board recommended that the ‘Adverse events specially tributed to NHLBI stop the tal before enrolling Primary End Point PACzoccurred ip9 patcnts inthe PAC 500 patients due to concems of early Use of the PAC did not affect the pri- group and 1 patient in the clinical as- adverse eventsand the unlikelihood of mary end point of days alive out of sessment group later receiving a PAC (©2005 American Medical Assoc 1, All rights reserved. (Reprinted) JAMA, Oct 5, 2005 Nol 294, No 13-1637 jamanetvrork.com by a Mexico | Access Provided by JAMA. User on 06/07/2023ESCAPE TRIAL OF PULMONARY ARTERY CATHETERIZATION EFFECTIVENESS ‘Table 1, Bassine Characienrocr of Randomned Patents and Patents Recenang Pumonary Artery catheterzation AC) Without ‘Randomizaton in ESCAPE Trial ‘inal P vas, ‘Assessment Group Randomizad Characteristic nazi) vs Rogistyt Keemaan Shy SET Dar ie. TE ro Face, Nos inte 42 0 inorty Ehotgy, No Teche oo 6 eoncharn Faeroe, neon SO) basta a ection Faston, mean SO), ca ‘yale blood pressure, mean SOL mn FG oe Secham, mean SD, meaL oor Teanga ren SOL a = oy ‘reainine, mean 80), maya 7505) BD oar w2i9 ‘azaina BNP. mean SOT pared Tore (409 % 1 wh Peak vo, mean SD) TOZ Ea) aazo na Ni nse) Sanwa mean SOT 0 oo) 1 wm asaina MLA soar aan SO TET ca 1 cof Hospitalization” odynaric Measurement Fig ail presse, mig ‘Systemic vascular resslance ches x seoTa Impact of Therapy Guided by Pulmonary Artery Catheterization During the Course Daa Fal TOU) ia] (Taste 6). These specific events were PAC-related infection (+ patients), bleeding (2 patients), catheter knot- ting (2 patients), pulmonary infarction’ hhemorthage (2 patients), and ventricu- lar tachycardia (1 patient). There wer no hospital deaths attributed to the PAC. Adverse events, most commonly infection, occurred in-hospital almost twice as often in the PAC patients, but ‘occurred in 143 patients in each group lover 6 months, Other cardiac proce- 1628 JAMA Ocober 5, 94, No. 1 Reprinted) dures occurred in 81 (38%) patients in the PAC group and 89 (4 clinical assessment group during hos- pitalization, fm the Secondary End Points Natriuretic peptides decreased stmi- larly in both groups. Punctional end points improved significantly during hospitalization in both groups, with 3 wend for more improvement in the PAC group (Ficune 4). The Minnesota Liv- ing with Heart Failure questionnaire improved in both groups by 1 mont ‘with greater improvement in the PAC ‘group. By © months, scores in the elini- cal assessment group had improved to match the PAC group. The time trade-off showed greater improvement for the PAC group com- pared with the clinical assessment ‘group at all time points (1, 2, 3, and 6 months; P=.001--02). By the end of the study, the average improvement (de- crease in survival months to be traded forbetier health) was 6.2 months in the PAC group compared with 0.9 months in the clinical assessment group. Ber clitremained if LV assist device oF trins- plant patients were given the worst score (P=.03-.05). When the missing data were modeled using the newly d seribed method of Davidian etal" the results were no longer significant, but the effects rended in the same direc- lion. The exploratory secondary end point of direct ime trade-off-adjusted. (©2005 American Medical Association, All rights reserved.ESCAPE TRIAL OF PULMONARY ARTERY CATHETERIZATION EFFECTIVENESS Bassline Discharge __Change __—_—Basoling Discharge __Change aa eSTeIa 808 BOs) wees wae ey ‘Syalole Bocd REIS AMT TOS TORT, TORTS TORT, TATE tated gulr venous pressure Amn TF iA et 125 Tae aaa Eerag Tae 77 Tipe ao Ta Zeya eat Greatnina naa 75 08) 750500 a) 7509 Or oat Teantegen me 3a 37 2a 302 zeit Seciun, mEgL TESS Ty TSO area eae TAT Symptom score aba Te 320) It “aT 35 20) 2 at ‘rthoprea scab) aan Tay —ta(iar Saat survival was dominated by survival and was neutral ‘COMMENT The ESCAPE trial selected « popula- lion more severely compromised than any other NHLBI-sponsored trial of medical therapy in patients with heart failure. The addition of PAC monitor- ing to clinical assessment had no over all effect on the primary end point, Although there were more adverse events in-hospital associated with the PAC, there was no excess early mor- tality. There was a consistent trend for greater functional improvement alter therapy guided by the PAC. Neutral Impact of PAC on Primary End Point The absence of benefit for the PAC on the primary end point could have re- sulted from multiple factors listed b low, as anticipated in the original de- sign.” Safety Previous retrospective studies raised the possibility that the catheter itself was associated with sufficient adverse events to influence major outcomes." The PAC, as used by the investigating sites, in ESCAPE, appeared overall tobe sale. The results suggest that retrospective reports of excess mortality with PACs (©2005 American Medical Assoc ton, Al rights reserved. were confounded by the severity of clinical status leading to the decision to use PACS, This is supported by the more severe clinical compromise in PAC registry patients in this study (Table 1). In ESCAPE there were only © (4.2%) direet procedural complica- jons, which may reflect both exper enced sites and specific edueation prior Impact of Therapy ‘to Reduce Fil In the PAC group, therapy tailored 10 approach a PCWP of 15 mm Hg and a right atrial pressure of 8 mm Hg re- duced these pressures effectively Marked clinical resolution of the signs and symptoms of congestion occurred in both groups (Table 3), providing a benchmark for the effectiveness of therapy during hospital failure. The accuracy of skilled inves- igators in clinical assessment of fill- ing pressures may have been adequate to identify and monitor the clinical in- terventions required without precise he- modynamic confirmation, The prognostic importance of achie ing low PCWP at discharge has been previously described."*** The relation between filling pressures and mortal- lty likely reflects multiple interactions with disease progression.” As in prior fs not possible to deter- ion for heart experiences, jamanetvrork.com by a Mexico | Access Provided by JAMA. User on 06/07/2023 (Repited) IMA, Ocober 5, Figure 2. Comustve Prmary Ena Port (Daye Alive and Out of Hospital) e 2 5 3 ‘Cimutave proporn of pate cntibuing each porsle nomen cutzoms rhe numberof dsp {er dead noc ospalaed dng the 20 pessbedays ffolow-up Patents thea et sé of ecu represen en eats, hiethasecourledas 18D dys ‘Shuved for month without enospaszsbon. The {ares frthe eater ouns puna ate ath ter PAC) pus neal sessment and cases. ‘ment onl are superposed mine whether achievement of lower fill. ing pressutes actually caused better out- ‘comes or merely identified patients with more favorable outcomes regardless of therapy Choice of Therapi Benefit derived from the PAC might have been offset if knowing hemod namic information triggered excess use ‘of medications with deleterious conse- quences. Such dilferences appeared toESCAPE TRIAL OF PULMONARY ARTERY CATHETERIZATION EFFECTIVENESS result from PAC use following sur Figure 3; impactor intervention on Pamary Ena Powt Acton: Demographic Suberoure s i rape SU EFOUP gery. Differences in use of intrave- Ton | Fo nous vasoactive agents did occur inthe eet | saw ESCAPE study and may have allected ovat = mortality.» but there was no benefit of wey oo PAC use om the primary end point, even Ss a for patients who received neither in- ae won a lravenots inotrople nor vasodilator roe vo — therapy (Table 5). The possibilty "he os mains that potential benefit of hemo- dynamic information was obscured by tae ex Lm variability in how therapies were ad- a ‘a — justed in response. to io 2 ‘Comparison With Previous Results oF Zo in Advanced Heart Failure cas to There have been no previous random- ed trials of therapy tailored during ‘retard alo ore pan ee pont ol dye he dad vo Faglaied rowed orabgiage continuous hemodynamic monitor- Ried on prranomasion cucansce Acinalesnaiec nce te catacnecasaboeorSe- ing in heat failure, Use of an indwel iow’ wa part ote tration equred tom he ergs prio adoration Tec {Sinere ddd athe nando ences asad on te sunte patent anonaedConpice img PAC to adjust therapy in advanced enon ntayaniebsstazaicn were vaube fr patenewnwereuiaaranayasclep heart failure was first described by trae pont : ” “Three patients did not have a cinical estimate of cardiac index recorded at the time of randomization. Kovick et al” and subsequently by Pier- pont for vasodilator therapy tn de- | opened heart failure with high Primary Outcomes: Mortality and Hosptalzations systemic vascular resistance. It be- TT Giricat cae common to assess reversibility of PAG Assessment End Point Estimate A Vie secondary pulmonary hypertension Measure Grou “Group cr et during transplant evaluation, for which {Wabetrereroniseoded 12 195 Head ati, 0.00 99 reduction of LY filing pressures is eru- ‘ead 00 (821.2) cial. The approach of tailoring therapy TiADetrarepianis coded a3 Fina to. TBD Fo reduce liling pressures was then ex- al 0.0 082-4.21) i ioraityaeadat 8G, No. 4335 Oise, 05 a5 ‘ended toimprove clinical status for pa- 126 072-203 Lents awaiting oF ineligible for tans- Tail daye Wal hoaptazalon, 87 83 Tsai, TIE BT plantation. Thisapproach, combined mean oe 861.27 With intensive outpatient heat failure Rete cet No o o NE TA NRT management, was associated with r ay cate hoop 77 Ti Oar, Dot — 97 . yas a Fe 309 duced hospitalizations, decreased clinic “ecnatare Gl eonhaence an CVAG I VEGUa AEE DANES NA, PeLOPRICSSET PAG paRcananen Cal congestion, and improved exercise et ‘capacity. ">" Similar experiences el: where demonstrated recognition of clinically unappreciated volume ove Ss rma End Fort Rens by notopeand Vasoulntr Ure Aer load and improved exercise expaciy Randomization when therapy was adjusted using PAC ee information” Primar e ed heart failure popula- coma pt The advanced heart flure popu Aacatitint —Mesid Sto pon and therapies have evolved since Grp Group Group OBC” Value hese experiences. Decompensation was Retepe t= Teg 730697 previously accompanied by severe var Nerobops ns 25F_— 80079 Soconstrction, such that aggressive vac Yesodator tied ncrops = 75_— 6670990805188 9E sedation in addition wo diuresis was @ am @ aquired to reduce filling pressures." “herring compares ates PAC qu anncalartcenert gp ere crugtestret gripe bent Patients now have longer duration of ‘Selerie'oumety sw tanertaercanpuc wtwrenoeauasauertempesnansase heart lure and ACE inhibitor use prior toadvanced symptoms, and many have $630 JAMA Cusoer 5,200 94, No. 1 Reprinted) (©2005 American Medical Association. All ights reserved. jamanetvrork.com by a Mexico | Access Provided by JAMA. User on 06/07/2023received Brblockers. The average sys- temic vascular resistance at baseline in ESCAPE was only 1500 dynes em’, compared with over 1800 dynes X sem: in several previous experiences.” However, progression of renal dys- function and diuretic resistance more commonly limits therapy that previ- couly.!" The average discharge furo- scmide equivalent was 180 mg, com- pared with less than 100 mg in earlier experiences." Current therapy during Ihospitalization fr heart faire now may focus lesson high illing pressures with ‘vasoconstriction and more on high ill. ing pressures with renal dysfunction. There have been 11 previous ran- domized trials of PACs in critical ill ness, in which the goals of therapy di- vverged from those described here for Iheart failure. 8 meta-analysis of these tral, including ESCAPE, showed athazard ratio of 1.00 for mortality and hospitalization.” The recently pub- lished PAC-Man trial of 1014 patients from varied practice settings in the United Kingdom also demonstrated no clfect on major end points in the ove all population or in the 11% of pa- tients with heat failure." These trials supportihe safety of PACS and the over~ llpeutral effect, while highlighting the challenge of assessing adiagnostic tool without a consistent strategy of re- sponse with effective therapies Secondary Functional End P« Punction and quality of life are eructal to patients with heart failure, a chronic debilitating disease. ESCAPE ts distinet from other trials of PAC, which have in- cluded patients during acute events with anticipated complete recovery. As re- vealed in our patients preferences, sur- vival is not the only, and for some not the most important, metric of benefit, While improvement in clinical status in both groups was substantial and sus- tained, a consistent trend suggested greater improvement in patients in ‘whom therapy had been adjusted using PACS. This could reflect the close rela- tion between filling pressures and syimp- toms of congestion. Exercise capacity has been shown to improve with reduction (©2005 American Medical Assoc ton, Al rights reserved. ESCAPE TRIAL OF PULMONARY ARTERY CATHETERIZATION EFFECTIVENESS ‘Table 6: Rovers Events n-hospreal ‘Adverse Event Tpisiatiecardovorer cerbrer Wing ‘Carcogerc ok iichemalargra Pic nfecion ypc niarcton Seeker ranent echarie aS Tardac arast Frecton Patents wih atleast Tacherse oo of filling pressures beyond that needed totreat edema.”*” The heart failure ques- Ldonnaire improvernent was greater by 5 points at 1 month in the PAC group, level that has been established as clini- cally meaningful to patients." The time trade-olf tool has only re- cenily been used to assess patients with heart failure" Primarily used in se- vere illnesses such as eancer, it corre lates with functional assessments and symptom scales, but with marked in- dividual variation. Some patients want survival at any cost, while others fo- ceus more on improving daily life than prolonging it! The improvement in the PAC group was more than twice as great atevery Lime point, suggesting that the patients awarded more value to their lives after therapy adjusted to lower fill- ing pressures. The time trade-off in- strument has shown a strong relation between elevated jugular venous pres- sure and willingness to trade time for beter health quality.” In ESCAPE, the average time to be traded out of 24 ‘months was9 months atthe time of ran- domization, confirming that patients with this severity of illness place high value on improving their quality of lie Applicability of ESCAPE Results There were no subgroups identified in which the impact of PAC use was si nificantly different from the overall tial The representation of 175 (40%) mi- nority subjects and 112 (26%) women suggests that similar considerations jamanetvrork.com by a Mexico | Access Provided by JAMA. User on 06/07/2023 Reprod) JAMA. Cxober 5 009) 53 28z ZB ‘Grange in secondary end pass presnted as an ‘ic eo th changes inthe 2 eaten grou. [ANP adiatestalnatrureic peptide: NP, anne ‘Ture peptide, VO, peak oxygen consumption MLA Mest Lig ith Heat are question: rae ana TT, time ade sore apply to PAC use in these groups. The population was defined specifically to exclude patients in whom PAC insertion seemed likely for urgent management ESCAPE centers were specifically se lected for experience with clinical and hemodynamic assessment during therapy for advanced heart failure. The ESCAPE benchmark for clinical im- provement during hospitalization for heart failure derives from experienced clinicians, recognized to be more ac- ccurate with both physical assessment and interpretation of hemodynamicESCAPE TRIAL OF PULMONARY ARTERY CATHETERIZATION EFFECTIVENESS measurements.” The safety of the PAC procedure also applies only to experi- fenced centers, with a trend for better ‘outcomes in those with the highest en- rollment. With the absence of benefit for the primary end point, there is no rationale at this time to inerease the number of centers using the PAC for the management of heat failure Limitations Interpretation of the ESCAPE results is limited by the lack of definition of pre- cise strategy in response to the hemo- dynamic information obtained. There ‘was considerable variation between sites in use of medications. Exercise tests, quality of life questionnaires, and the lime trade-off uuility assessments were secondary end points, with missing data that could not be assumed to oceur ran domly. Challenge arises in interpret- ing positive findings among an array of secondary end points dominated by a neutral primary end point. Implications for PAC Use in Advanced Heart Failure Based on ESCAPE, there is no indica- lion for routine use of PACS to adjust therapy during hospitalization for de- compensation of chronic heart fail- ure, It seems probable that there are some patients and some therapies that yield improved outcome with PAC monitoring and others with counter balancing deleterious effects. The ESCAPE trial does not provide infor- mation on using PACS in cardiogenic shock or in triage for LV assist devices and cardise transplantation, For patients in whom signs and symptoms of congestion do not re- solve with initial therapy, consider- ation of PAC monitoring at expe tenced sites appears reasonable if the information may guide further choices of therapy. In ight of accumulating in- formation regarding the deleterious effect of intravenous inotropic therapy, the PAC might be used to guide thera pies for patients in whom inotropic therapy Would otherwise be used. The ESCAPE trial defined the most compromised patient population to be 4622 JAMA cXioher 5, 2005 Vol 204, No. 13 Reprinted) studied in an NHLBI heart failure trial with medical therapy, with 10% (83 pa- tients) mortality at 6 months. No di- agnostic test by itself wll improve out- comes. New strategies should be developed to test both the interven- tions and the targets to which they should be tailored. Although most trials in a high-event population have fo- cused on reducing mortality, patients with advanced heart failure express will- ingness to trade survival time for bet- ter health during the time remaining. How patients value their daily lives should help guide both the design and evaluation of new therapies. ‘Authors: Crying authors are members ofthe ete and Pubictbons const of the ESCAPE tna Autors/membes ofthe Execute and Pubes tons commits, study ivestgats, and coordina tor ae sted belo ‘Autor Contos: Or Stevenson had ful aces toallofthedatain te stuy and lakes esponszty fect integty ofthe data athe accuracy of the (ta ana ‘Stuy concept and desig: Stevenson, ©'Corner Clit, Sept, shah, Lee ‘Aeguiston of dat: Stevenson, O'Comner, Cat, file Sha, Hssebbad Frans Leer Branay. ‘Anaiysis an interpretation of dat: Stevenson, Gromer, Catt Sopk, Shah, Hasead, Francs Drafting ofthe manusenpt Stevenson, O'Connok Nile, Shan, Hessead Cita! even of te manus fr important in fect cntant Steveran © Connor, ai Spi, Shah Hass, Fares, Lele, Bnanay. Satis analysis Haseba, Obtained nding Stevenson, © Conner, Cat Shh, Cer ‘Aainistative, tecnica or material suppot- Cast, Septe, shan, Le, Snanay. ‘Stuy superson: Stevenson, Sopko, Shah Financial Diclosutes: None reported ‘Authors /ESCAPE Executive Comite: Cynthia FEnaay, A, BSN, Poet Leaersip, Duke incl esearch tute Dhar, NC: Rober M. Cl MD, Divison of Cadelogy, Duke Unveraty Msc Cen terang Duke Cineal Research Inst, Dura, NC ‘Vic rssllad, Pao, slosttsties and Biontormates, Due Cina eseeen Center, Duar, NC, Cin tepheM© Connor 1D, Dison of arog, Duke Uhiversty Meatel Center and Duke Clea! Re ‘euch neue, Duttam, NG Manca Shah MD, fas of Cardology Columba Un ‘es Medical Center New Yor NY. George Sop, Mp, MPH Dison of Heart and Vascular Dieses, NatonalHeart Lng ard od Ista, Nabonaln ‘tutes Meh, Senet Na LymeW. Severson, Mb, Cacsovascl Dison, Brigham ara Womens Hosptial Boson, Mass ‘Authors/ESCAPE Publications Commitee: Gay Francs, MD, Corry nesve Care Un. The Cleve len liseFounan, Cevaard, On Cul V-Leer, Mb, Dion of Cardovascuar Medene, Ths Oks StateUnversty, Cotumous LesieW Miler, MD, Dr ‘sion of Cadlogy, Unversity of Minnesota, reaools ESCAPE ste Investigators, tus Coordinators: Un ‘ery of Fang: mer i ID /Dsne Pay, Mb, Debra Olsh: Date University Medel Cen far Sua Russel, MDVChesopher MO Connor, MD, ‘Downloaded From: hitps:/ljamanetwork.com/ by a Mexico | Access Provided by JAMA. User on 06/07/2023. Beth Paterson: LAC-USC: Us Ekayam, MO, Saknan Kan; Brigham and Women’s Hrpta Lynne W. Stevenson, MD, Kimber Brooks; Unies of Ci ‘nat Lyne Wagoner MD, Ginger Cony Un ety of Mga To Kong Mi, Cara Van uy Senden Hops Jshus Hare MD, Eayne Beton The Unversity of Nar Carling Kio FA {ine MD, ans te UCLA Greg Foaro, AD Male Harton, MO, be Srg UT Seutrwest: Mark ramet, M®, Shannon Hetiman: Univesity of Minesota Leste W Mile, MD uth A. Crazano, Mar len Seman: Mayo Cini Robert Fant, MO, en Hata The Oe Slat Urry Ca Leer MO /Wita Abra MO, Laur amok Mase Genera: Thomas G. Dale, MD, nce Camo Nvthwest: Mina Gheorghiade, MD, Karen Fa Chet sh Peston: ln Here, MD, So Kir University of Clg Waype Warne MD, Jane Geant: Unversity of Ketucy Mian Haan, MO, Uy da With he Cleland Cine Foundation: ames Young MO, ature Gus Vanderbilt Unversty Javed ute MD, Laue Hains: Unversity of Alabama Bary Rayburn MD esis Reisen: Unvarty Hs abot Cevelan leanaPAa MO, Lr Shey Wash ington Univesity: lose Rogers. MD, Hei Cad dace Arabi Heat Mein Tonk, MD, Shane er UcS Teresa DeMarco, MD, Bebre Lu; Un sty of Wisconsin: Mary oesor, MD, Cssngta Vander Ak ations Team: Wanda Tate, A, Mae! ison, Neva ayes Gusye Tass PHD Var ir row, MD, andy ana. RN BSN, Duke Cn (2 seach Inst Durham, NC Finding Supper: Tis research was supparey con {oct NOCH E77 frome Nationa Hea Lng, 2d Seed nate o Duke Unversity Medes Cente Role ofthe Sponsor: The Natonal Hear, Lang, and ood nse oversaw the formulation and st {itso hecataandsatty mostorng board DrSopko Cenknoutedt the al design and oxecton and pa. {tpate nthe anayss of the data and preparaton of he manasa EARNS 4. Cot IN, lhnsonG,Zesche 5, ea A compa Sén of enlaprih hyilazne: soso aifate'n ‘hetresment of con congestve er are. NE ied 1991395 903210, 2. The SOLD investigators ect of nla on a ‘alm patents with reduced let verte ecton actions and congesve heat alte. Wag! Med, 1351 325283-303 3: Pat, Zannad Remme Wh tat Randomied A Glictone Evaluation Stuy lnvesigatos. Te eect of Spraladone on morally ana mortality In paberts severe ea fale Ng Med. 999° 703. ww. 4. Packer Coats Al Foner Ma, ta Caneel Pro ‘Seve Randomaed Cumustv Suro Sty Grup, Effect of caved on sunoaln severe cei heat {alu Neng) Med 2001 34416511688" 5. Fonz OC, Adis, Asana WT, Yancy CW, Boscardin Wl, ADHERE Scenic Advisory Comet {ee Study Group, an lvesigates sk stallcaton {erinnospal meray acl decompensated heat {ale seston and regresion tie aay JAMA 2005,293572-580. & Lee DS. Austin PC Rouleau LLP, Numark, Tu Precting macalty amen pais host inedorhet ale devaton snd vaiston en. ‘elmodel Atta 2003.90 2581-2587 7. Rose A, Clips AC Mestowtz le Random ‘ed ralstn of Mechanel Asan forthe Te rent of Congestive Hea fale (REMATCE) Sy ‘Group. Long tem mechanical left ventrear asi {ane fore stage eat false ng J Med 200 eaten, (©2005 American Medical Association, All rights reserved.8 Stevenson LW, Tisch Maintenance of adc ‘put wih norma ling pesuesin pent at leg ner faze Craven 986419031308 5: Severson LV, Brunken RC, Belt Aeond ‘eduction wth vada and uses decease {ralregupaion dng up execs in avanced hea fale. Am» Co Caso. $990;95:174 18D 4, Stevenson LW, ieeemaK Talat Het xe secapacy fr sir ocardactranslraion oF Sustained medal teray for sable heat flue. teultion 195,878 {HU Stmle AE Stevenson LW, Chlimsty-Falik C, tal Sustained nemodyrami efacy of therapy {auoed to reuce ling ese In suvors with SGvanced hea flute Craton 99796 965" i172 ‘2, Hamiton MA, Stevenson LW, Chi, Marg hiJD, Walden, Woo M.Sustaned reduc inv ‘alr egutaton and ati volumes witalred ‘alate m sovanced congestive het are Secondary to diated (ischemic or iigpathe) adomyepaty. Am] Cardo 12915725263, $3: Rowan Ly teveson UW, Solomon SD Lee RT Reimod SC. The mechan of dace n ynaric ral regugiaton aang heart are eaten Pofaneeofreaucton i the regurgtant oc ize. Foi Col Cao. 19832-1819-624 1 Fonron Gc, everson LW, WalenJA etl cof acomprenae ea ate mar ‘amon hosplaleadmtson and uncial turf Pate ih advanced Pet lem Col Cardo fss730725.732 45, Fenrow CC, Celis alle, Stevenson LW, tat efecto ret asodsion with hyrasane ver $s angotersh-convetng enzyme non thcap {opal on moray advanced heart fale the 9). {nal Am Col Cad 1959:19842-850 46, Connors AP Ie Sper, Danson NV a SUP PORT nvesgatars The ceiver of rhea ca ‘eration bce fers pte JAMA fwse276 385-097. 47. Dalen, Bore RC; eit ine to pul the pumo- ay ater caver? JAMA, T956.76916-518, {shah RO Coner CN, SpkoG, Has, Ctirti Stevnsan LW. Evasion Study of Con” geste Heart Flue and Purmonary Arey Cab [Etontfetieness ESCAPE cesgnandraonak. An Har | 2001141528535, 4 tier V, Wemner DH, Yusu ,e a SOLVD UhvesgtasPredcton cfm andor wth ‘emiute wal este patents with et vente (pstuncn JANA 1998-270: 1702-1707. 20. Rector, Tschumperin LK, Kubo SH, eta Use of ne Lng in Hea Faure questonase fo a eran patents pespecveson improvement aa lyfe versus sof rugndued deh. J Card al. 1395 1201-06 21 Ley EF lobnzon PA, ohneon W, Cots CG fin, Stevenson LW. Peterence for guy of fe of ‘Sv expres by pers wih at alle Heart lrg Tarp 2001-20 1016-1028 22: Lank, Cordon, Deets DL Decree sequential boundaries 1983 10659 63 (©2005 American Medical Association, All rights reserved. ESCAPE TRIAL OF PULMONARY ARTERY CATHETERIZATION EFFECTIVENESS 23. Davidian M, Tabs Leon. Sem-paametc es ‘Gratin ofteatnenteffectin apres potest std ‘wah mang data St Sa 200520261301 24. ore Gober Rl. Spock Apert 5, Den 5 Acommaniy-ie assent of the seo ul monary ater catheters mpaberts with acute myo (hea Warton. Chest. 198792724727 235. Don Mi Ban). Roenman Oye ak SPRINT Sty Crap, Uso pumonayatey catheters pa ‘ent with acute myecrda ncn: anal fe Pelener nS pans ntheSPRINT Regs, Chest ‘Sooseraa1-1s35 26. Stverson LN, fh JH, Hamiton Mt. In poitance of emedynamic sponse to therapy preclng sual wth eect facta es than 0” ‘ua to 20% secondary to Scenic or nonheme lated cardiomyopathy. Am 1 Cardo 199066 Saae3s 27. Campana C, Cava A, Bez, ea Pei {ers of poanoss in pabantsawating heat tans lstaton Heat Lung Transplant 1993:12756 fa 28. Aaronson KD, Schwa IS, Chen TM, Wong KL, Gein Marci OM. Devoprent and prospective ‘aidan fa cca ndoe to predel sual nam latory patient referred fr eardiae waneplant srauson, Craton 199798: 2660 266. 29. Kaje GM Lambert QM, Leto Mare fangs, Ber MD. Neurochem enence of aac Spoatete action and ceased cet ners Stem reepnepsnetumover in severe cngesve feat alure on Cal Cadel 199833 570578, 3. Kero, Keto, Kis, tal Maha sd ing simulates cel rypervophy and soectic gene ex Peston cutured a cwdac myocytes pose le ‘fpr nae Cactvatin Bol Chem 1291-256 ‘es 2c 31 Let A Cla P. LO, et a. Stetch- mediate eles of ingots induces myo spoposs by {ctvating p53 that enhances the lea rain Angolendh stem and dere te Bl? too pro {nraomthecel Jl ives. 19581011926 502 32. Sanda Hul RD, tat ta Canaan Cr ‘alcare lal Tas Coup A andonzed controled {a of use of pulonany-ater cates nh Fk surge pens Mg)! ed. 2005 3485-14 5. Sehneedertein dD Kowa M Fox, Ato {nk Shorter kot death ater tesrent thine Sie fr cecompersated ea tala pooled aay Set randonaed convoles als JAMA. 2005295: 500-1908, 4H. Kove RE, Tisch Berens SC, Bamowit AD, Shine Vasoaltor therapy forever lta, Celaton, 197493:322-308, 35. Pepont CL. Medal management of terminal ‘aréomjopahy./ Hen Transplant 98321827 56. Steverson LW, Dracup KA Tisch IH cay of imei therapy tard for severe congestive hast {lure in patents transfered for urgent eadiae Uarspnlaben. Am Carol. 198,63:861-464, 37. LuasClohrson W Hamiton MA, ea Fre Gomironcongesionpredcsgeodsuvaldespie re ‘ous das V Symptoms of heat fare. Am Hea doonowe Ber ‘Downloaded From: hitps:/ljamanetwork.com/ by a Mexico | Access Provided by JAMA. User on 06/07/2023. 38, Stevenson LW tin AE Foraow Ga. proverentn xersecaacty of eanddates awaits Feat tansplantation. Am Cll Cardia. 1995, 1e-170. 38. Chars DB, Lang CC, Rayos, Wison Treat ‘ent subene ul etenton peers th symp ‘Sma heat fue effect on ence performance. ‘Heat Lung Tanai 19571846053, fan. raze MH, Harton MA, Foraon C, Ceaser [Fava Stevenson LW Relaborsh between it nd sed ling presses 1000 pati wi a ‘anced eat le Hea Lung Tapa 19:18 raes32, 41. Wahid MS, Cetow GM, Stevenson LW. Ag {avatedrealdytunciondcngintnse therapy tt {rancedcronc hen fate, A Hen). 1980138 pe5-090 {titer Forman DE Abraham WT etal Relation Ship between heat flare Ueatment ard develop rent of woseing eal uncion aang hosptalzed Duets Am Heart J 2008147331338 {3 Bener Sth ees MA ones CE Routine pa ‘ana artery catheteteation doesnot educe mo Baty and mavalty of elective vasclr surgery re Sasol pospecive randomized tal An Sut 197 bae09 236 1 defauF,Abrame IH, Gimou Ul, O'Connor SR Kighton DR. Cera. Preoperative option of (arsovasalar hemodynamics proves cucomel pe "eta sedge a pospectne, anomie lal A Su 1951314 289-297 1S. 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