Relationship of Right- to Left ... - Circ: Heart...
Transcript of Relationship of Right- to Left ... - Circ: Heart...
1
Relationship of Right- to Left-Ventricular Filling Pressures in Advanced Heart Failure:
Insights from the ESCAPE Trial
Drazner et al: Ratio of RAP to PCWP in Advanced Heart Failure
Mark H. Drazner*, MD, MSc; Mariella Velez-Martinez*, MD; Colby Ayers†, MS;
Sharon C. Reimold*, MD; Jennifer T. Thibodeau*, MD; Joseph D. Mishkin*, MD;
Pradeep P.A. Mammen*, MD; David W. Markham*, MD; Chetan B. Patel‡, MD
Division of Cardiology*, Department of Internal Medicine, and Department of Biostatistics†,
University of Texas Southwestern Medical Center, Dallas, TX
Division of Cardiology‡, Duke University Medical Center, Durham, NC
Correspondence to: Mark Drazner, MD, MSc University of Texas Southwestern Medical Center 5323 Harry Hines Blvd, Dallas, Texas, 75390-9047 E-mail: [email protected] Telephone: 214-645-7500 Fax: 214-645-7501
DOI: 10.1161/CIRCHEARTFAILURE.112.000204
Journal Subject Codes: Heart failure: [11] Other heart failure
am, NCNCNCNCNCNCNC
lvd Dallas Texas 75390 9047
: MSc SoSoSoutututhwhwhwwesesesesteteteternrnrnrn MMMededededdicicicicicalalalal CCCCenenenenteteter r r rlvlvdd DDalallalass TTexexasas 7575393900 90904747
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
2
Abstract
Background—Although right atrial pressure (RAP) and pulmonary capillary wedge pressure
(PCWP) are correlated in heart failure, in a sizeable minority of patients the RAP and PCWP are not
tightly coupled. The basis of this variability in the RAP to PCWP ratio, and whether it conveys
prognostic value, is not known.
Methods and Results—We analyzed the Evaluation Study of Congestive Heart Failure and
Pulmonary Artery Catheterization Effectiveness (ESCAPE) database. Baseline characteristics
including echocardiographic assessment of right ventricular (RV) structure and function, and
invasively measured hemodynamic parameters, were compared among tertiles of the RAP/PCWP
ratio. Multivariable Cox proportional hazard models assessed the association of RAP/PCWP ratio
with the primary ESCAPE outcome [6-month death or hospitalization (days)] adjusting for systolic
blood pressure, BUN, six minute walk distance, and PCWP. The RAP/PCWP tertiles were: 0.27-0.4
(tertile 1); 0.41-0.615 (tertile 2), and 0.62-1.21(tertile 3). Increasing RAP/PCWP was associated with
increasing median right atrial area (23, 26, 29 cm2, respectively, p<0.005), RV area in diastole (21,
27, 27 cm2, respectively, p<0.005), and pulmonary vascular resistance (2.4, 2.9, 3.6 woods units,
respectively, p=0.003), and lower RV stroke work index (8.6, 8.4, 5.5 g-m/m2 per beat, respectively,
p<0.001). RAP/PCWP ratio was associated with death or hospitalization within 6 months [HR 1.16
(1, 1.4), p<0.05].
Conclusions—Increased RAP/PCWP ratio was associated with higher pulmonary vascular
resistance, reduced RV function (manifest as a larger right atrium and ventricle and lower RV stroke
work index), and an increased risk of adverse outcomes in patients with advanced heart failure.
Key Words: hemodynamics, heart failure, right ventricle, renal function, pulmonary hypertension
ssssococccciaiaiaiaiaiaiatititititititiononononononon ooooooof ff f f f f RARARARARARARAPPPPPPP
CAPE outcome [6-month death or hospitalization (days)] adju t
N e
5 a
ght atrial area (23, 26, 29 cm , respectively, p 0.005), RV area
CAPAPAPAPAPE EEEE ouououououtctttt omomomomome [6-month death ooooor r hospitalizatioioioioion (days)] adjust
N, ssixiiii minutte e waallk ddddiiisii tanccee, andn PPPCWCWWWWP.P.P.PP TTThehee RRAPAPAPP/PPPPPCWWWWWPPP tterttile
5 (tertile 2), and 0.6.6.6.662-2-2-2-2-1.1.111 2121212121(t(tt(ttererere tileee 33333))))). IIIIIncncccrererereasasasasa inininining gg RAP/PCWP wa
ghghtt atatririalalalll aarereaa (2(2(2(2(23,33,3 22226,66,6 222229999 cmcm2222,, rerespspecectititit vevvelylylyll ,, p<<p<<<0.0.0.00 00000000005)5)5)55 ,, RVRVRVRVR aarereaa
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
3
Elevated right-ventricular and left-ventricular filling pressures contribute to many of the
symptoms of patients with advanced heart failure. In both systolic1 and diastolic2 heart failure,
right-ventricular filling pressure (i.e., right atrial pressure, RAP) is significantly correlated to
left-ventricular filling pressure (i.e., pulmonary capillary wedge pressure, PCWP). This
relationship is robust enough such that estimation of the PCWP is often based upon assessment
of the jugular venous pressure (JVP) in patients with heart failure.3 Further, the relationship of
the RAP and PCWP has been shown to be stable over a 14 year time period (1993 to 2007) in the
Cardiac Transplant Research Database (CTRD), a registry of patients with advanced heart failure
undergoing cardiac transplantation.4 However, in a sizeable minority of patients with heart
failure (25-30%), the RAP and PCWP are not tightly coupled.4, 5 The basis of the variability in
the relationship of right- to left-sided ventricular filling pressures (which can be expressed as the
ratio of the RAP to PCWP)4 is not well understood. Further, whether the ratio of the RAP to
PCWP is associated with outcome in the broader advanced heart failure population, as it is in
patients undergoing left ventricular assist device implantation6 or cardiac transplantation,4 has
not previously been assessed to our knowledge. The ESCAPE (Evaluation Study of Congestive
Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial, in which patients with
advanced heart failure underwent careful hemodynamic and echocardiographic assessment, as
well as longitudinal follow-up, afforded an excellent opportunity to further define the
physiologic basis and prognostic utility of the ratio of RAP to PCWP in this patient population.
ority of patienntststststststs
Theheeeeee bbbbbbbasasasasasasa isisisisisisis ooooooof f f f f f f thththththththe
i
P f
i
ighghghghghttt- to lelelelel ftftftftft-s--- ididididdededededed vvvvenenenenentrtrtrtrtriciciciccululuulararaaa filllliinggggg ppppprererereressssssssssurururu eseseseses (whwhwhwhwhiciciccich hhhh cacacacacan n n nn bebbbb
PCCCCCWPWPWPWWP)))))44444 is ssss nonononn t tttt wwweww llllllllll uuundndndndnderererererstststststooooooooood.dddd FFFFFurururururthththththererererer, whwhwhwhwhetetetetetheheheheherrr rr thththhtheee ee rararararatitititt o oooo ofoofoo
wwwititithhh ouououtctctcomomomeee ininin ttthehehe bbbrororoadadadeeerrr adadadvavavancncncededed hhheaeaeartrtrt fffaiaiailululurerere popopop pupupulalalatititi
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
4
Methods
ESCAPE Trial
The ESCAPE trial assessed the effectiveness of right heart catheterization in hospitalized
patients with New York Heart Association (NYHA) IV symptomatic heart failure. Patients had
to have left ventricular ejection fraction 30%, 3 months of symptoms despite ACE-inhibitor
and diuretic therapy, a systolic blood pressure 125 mm Hg, and at least one sign and one
symptom of congestion. Of the 433 patients randomly assigned, 215 were assigned to the
pulmonary artery catheter arm. The trial was conducted in the United States and Canada between
2000 and 2003 at 26 sites. The primary results of the trial have been published.7 The protocols
were approved at each site and written informed consent was obtained from all patients prior to
randomization. This analysis was conducted with a public release of the ESCAPE database.
Right heart catheterization and hemodynamic classification
The sites participating in ESCAPE were selected for known expertise in invasive monitoring and
clinical management of patients with HF. Paper printouts were used for hemodynamic
measurements. Cardiac output was measured by thermodilution in triplicate. In this analysis, we
assessed both the initial hemodynamics and the final hemodynamics at right heart catheter
removal. The average length of time the right heart catheter was in place was 1.9 days. We
excluded three patients due to measurements that were extreme outliers possibly due to
erroneous data entry: two with baseline RAPs of 71 and 85 mm Hg, respectively, and one with
PCWP of 0 mm Hg. Subjects were classified into tertiles of the ratio of RAP to PCWP: 0.27 to
0.40 (tertile 1); 0.41 to 0.61 (tertile 2); and 0.62 to 1.21 (tertile 3).
een publishedddd.......
taineeeeeeed d d d d d frfrfrfrfrfrfromomomomomomom aaaaaaallllllllllllll p
E
e
anananananalysisssss wwwwwasasasasas cccccononononondudududuductctctctctededededed wwwwwitititiithhh a ppubbbbblililililic cc cc reeeeelelelelleasassasaseeeee offfff ttttthehehehehe EEEEESCSCSCSCSCAPAAAA E
erererizizizatatatioioionnn anananddd hehehemomomodydydyynananamimimiccc clclclasasassisisififificacacatititiononon
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
5
Echocardiography
Details of components of the echocardiographic examination in ESCAPE have been published.8
In brief, echocardiograms were performed within 24 hours of right heart catheterization.
Echocardiograms were analyzed at the core center at the University of Texas Southwestern
Medical Center. Measurements were performed offline by a single sonographer or physician in
accordance with the criteria of the American Society of Echocardiography, and were made in
triplicate and averaged. Measurements were obtained from the apical 4-chamber view (right
atrial area, RV area at end-diastole and end-systole, left atrial area, mitral regurgitant color jet
area, and left ventricular end-diastolic and end-systolic volumes by Simpson’s method of discs),
and subcostal view (inferior vena cava size in inspiration and expiration). Derived measures
included left ventricular ejection fraction, right ventricular fractional shortening [(RV area
diastole- RV area systole)/RV area diastole], and the ratio of the mitral regurgitant color jet area
to the left atrial area.
Variable definitions
Creatinine clearance was estimated by the Modification of Diet in Renal Disease equation.9
Transpulmonary gradient was calculated as mean pulmonary artery-PCWP. Pulmonary vascular
resistance was calculated as transpulmonary gradient/cardiac output. Right ventricular stroke
work index was calculated as (cardiac index/heart rate) x (mean pulmonary artery pressure-mean
RAP) x 13.6. Pulmonary compliance was calculated as stroke volume/(PA systolic pressure-PA
diastolic pressure).10
by Simpson s s mmmmmmm
piratatttttioioioioioioion)n)n)n)n)n)n)...... DeDeDeDeDeDeDeriririririririvevv
u
ystole)/RV area diastole], and the ratio of the mitral regurgita
uuuuu alalaaar ejecccctiiiiononononon fffffrararararactctcttctiooooon,n,n,n,n, rrrrrigigigigghthththt vvennntrricccccululuululararararar frfrfrfrfracacaca tititititionoooo alalalalal ssssshohohohohortrtrttrteneneneneninininining gggg
ysttttololololole)ee)ee)/R/R/R/RRVV VVV ararararareaeaeaeaea ddddiaaaastststststololololole], ananananandd ddd thththhhee eee rararararatititititioo ooo ofofofofof ttttthehehehehe mmmmmitittttrararararal llll rrrerr gugugugugurgrgrgggittitttaaa
..
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
6
Statistics
Data are presented as median (interquartile range) or number (percentage). To compare
characteristics across ordinal, increasing tertiles of baseline RAP/PCWP, we used the Cochran-
Armitage trend test for categorical variables and the Jonckheere-Terpstra trend test for
continuous data. The chi-squared statistic was used to assess any overall racial significance.
Spearman correlation coefficients were calculated between baseline RAP/PCWP and other
invasively measured hemodynamics. Outcome analysis was with the primary outcome of
ESCAPE, number of days alive outside the hospital at 180 days post randomization. In a
secondary analysis, we used overall morality as an outcome. Patients who underwent
LVAD/transplant were treated as dead in 1 analysis and were censored in another analysis. For
the outcomes analysis, we excluded patients who were lost to follow-up (N=5). After observing
no trends with time for the Schoenfeld residuals, Cox proportional hazards models were used to
assess hazard ratios for a 1 standard deviation increase in the RAP/PCWP ratio in both
unadjusted and adjusted analyses. For the adjusted analyses, model 1 adjusted for six minute
walk, BUN, Systolic blood pressure. Model 2 adjusted for the covariates in model 1 with the
addition of PCWP. Two-sided probability values (p-value) were used in all statistical analysis
with a p-value <0.05 considered statistically significant. All statistical analyses were performed
using SAS (v. 9.2; SAS Institute, Inc., Cary, North Carolina).
Results
The distribution of the ratio of the RAP/PCWP is shown (Figure 1). The median (interquartile
range) was 0.50 (0.37, 0.68). The RAP was significantly correlated with the PCWP (r=0.59,
p<0.001). The ratio RAP/PCWP measured on the initial hemodynamics was significantly
ents who undderererereree w
nsorrededededededed iiiiiiin n n n n n anananananananototototototothhhhheheh
s A
f e
siiis,s,s,s,s, we exxxxclclclclludududududededededed pppppatatatatatieieieieientntntntntsssss whwhwhwhho o wewwereeee lllllososososost t tototototo fffolololololloll w-w-w-w-w-upupupupup (N=N=N=N=N=5)5)5)5)5). A
for rrrr thththththe eee ScScScSS hohohohohoenenennnfefefeffelddddd rrrresesesssididiidi uauauauaualslslslsls, CoCoCooCoxx xxx prprprprpropopopopopororororortititititionononononalalalalal hhhhhazazazazazararararardssdsss mmmmmododododode
fffororor aaa 111 ssstatatandndndarararddd dededeviviviatatatiiiononon iiincncncrerereasasaseee ininin ttthehehe RRRAPAPAP/P/P/PCWCWCWPPP rararatititiooo iii
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
7
correlated to that measured on the hemodynamics measured at the time of right heart catheter
removal (r=0.49, p<0.001). Of subjects with baseline RAP/PCWP tertile 1, 12% had shifted to
RAP/PCWP tertile 3 when hemodynamics were reassessed prior to right heart catheterization
removal. Similarly, 11% of subjects with baseline RAP/PCWP tertile 3 shifted to final
RAP/PCWP tertile 1 (Table 1).
Relationship of baseline characteristics and renal function to RAP/PCWP ratio
Baseline characteristics are shown by tertile of RAP/PCWP (Table 2). Increasing RAP/PCWP
was associated with impaired renal function as evidenced by a higher baseline creatinine and
BUN and a lower creatinine clearance. Increasing RAP/PCWP was also associated with the
maximum in-hospital BUN (28, 33, 40 mg/dl), discharge BUN (25, 34, 35 mg/dl), and discharge
creatinine (1.2, 1.5, 1.6 mg/dl), respectively (p 0.005 for all). Increasing RAP/PCWP was also
associated with signs of right sided heart failure including elevated jugular venous pressure,
ascites and peripheral edema. In contrast, there was no association of elevated RAP/PCWP with
orthopnea and other clinical predictors associated with worse outcomes such as NYHA class and
systolic blood pressure.
Relationship of invasively-measured hemodynamics to RAP/PCWP ratio
Invasively measured hemodynamics (Table 3) are shown by tertile RAP/PCWP. Increasing
RAP/PCWP was associated with a higher right atrial pressure but was not associated with
pulmonary capillary wedge pressure. Subjects with a higher RAP/PCWP also had a higher mean
PA pressure, transpulmonary gradient, and pulmonary vascular resistance than those with a
lower RAP/PCWP. Cardiac index and RV stroke work index were lower in those with higher
gher baseline e ccrccccc
was aaaaaaalslslslslslsooooooo asasasasasasassososososososociciciciciciciatat
a l
P
u
allll l BBBUBB N (2(2(2((28,8,8,88 333333,3,3,3,3, 444440000 mgmgmgmgmg/d/d/d/ddl)lll , dididid sccchhargrgrgrgrgeeeee BUBUBUBUBUNNN N (2(2(2(2(25, 333334,4,4,4,4, 333355555 mgmgmgmgmg/d//// l
1.66666 mgmgmmgmg/d/d/d/d/dl)))l)l), rererererespspspspspecee tititititiveveeveelyllll (((((ppppp 00.000 0000000005 5555 fofofofofor rrrr alalalalall))))). IIIIncncncncncrerereeasasasasasinininining RARARARRAP/P/P/P/P/PPP
sss ofofof rrrigigighththt sssidididededed hhheaeaeartrtrt fffaaailililururureee inininclclcludududinining g g gg elelelevevevatatatededed jujujugugugugg lalalarrr vevevenononouuu
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
8
RAP/PCWP. In correlation analysis, RAP/PCWP ratio correlated significantly with RAP
(r=0.78, p<0.001), transpulmonary gradient (r=0.24, p=0.001), pulmonary vascular resistance
(r=0.23, p=0.002), cardiac index (r=-0.15, p<0.05), and RV stroke work index (r=-0.43,
p<0.001), but not PCWP (r=0.01, p=0.9). In a subgroup analysis restricted to subjects with a
PCWP 22 mm Hg, similar associations of RAP/PCWP ratio with invasively measured
hemodynamics were found including increasing PVR among those with increasing RAP/PCWP:
2.4 (tertile 1); 3 (tertile 2); 4.3 Wood units (tertile 3), P<0.001 (other data not shown). There was
no difference in administration of milrinone (p=0.75), nitroprusside (p=0.15) or dobutamine
(p=0.6) among tertiles RAP/PCWP.
Relationship of echocardiographic parameters to RAP/PCWP ratio
Echocardiographic parameters are shown among tertile RAP/PCWP at baseline (Figure 2).
Subjects with a higher RAP/PCWP ratio had echocardiographic markers of right ventricular
dysfunction including a larger right atrial area, right ventricular area in both systole and diastole,
and a larger inferior vena cava both in inspiration and expiration. There was no significant
association of RAP/PCWP ratio with right ventricular fractional shortening (0.25 [0.2, 0.3] tertile
1; 0.2 [0.13, 0.29] tertile 2; 0.21 [0.15, 0.28] tertile 3, p=0.2). There was also no significant
association of the RAP/PCWP ratio with left atrial area, tricuspid regurgitation velocity, LV end-
diastolic or end-systolic volume, LV ejection fraction, or ratio of mitral regurgitation to left atrial
area (p 0.2 for all; data not shown).
h
p (
h t
hoooooccaccc rdioooogrgrgrgrgrapapapapaphihihihihic c c cc papapapaparararararamemememm teeeeersrsrrr too RARARARARAP/P/P/P/P/PCPCPCPCPCWPWPWPWPWP rrratatatatatioioioioio
parararararamememmemetetetetetersssrsrs aaaaarerereee ssssshohohohownwnwnwnwn amomomomomongngngngng teteteeertrtrtrttilililleee ee RARARARARAP/P/P/PP PCPCPCPCPCWPWPWPWPWP aaaaat tttt bababbb seseseseselililinenenenene (
hhhererer RRRAPAPAP/P/P/PCWCWCWPPP rararatititiooo hahahaddd ececechohohocacacardrdrdioioiogrgrgrgg apapappphihihiccc mamamarkrkrkererersss ofofof rrrigigighththt
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
9
Relationship of RAP/PCWP ratio and outcome
The association of the baseline and final RAP/PCWP with six-month outcome (Table 4) is
shown. In the whole cohort, increasing baseline RAP/PCWP was associated with death or
hospitalization (days) in a model adjusted for six minute walk, systolic blood pressure, BUN, and
pulmonary capillary wedge pressure. The correlation between RAP/PCWP and PCWP was
statistically insignificant, and thus multicollinearity was not an issue. In the subgroup of subjects
who had elevated PCWP ( 22 mm Hg), increasing baseline RAP/PCWP was associated with
death or hospitalization (days) both in univariate and multivariable analysis. In analyses in which
the final RAP/PCWP ratio was substituted for the baseline RAP/PCWP, qualitatively similar
associations with outcome were noted. In our secondary analysis using six-month mortality as
the outcome, the event rate in increasing baseline RAP/PCWP was 16% (tertile 1), 21% (tertile
2), 29% (tertile 3), p=0.09.
Discussion
Although right-ventricular and left-ventricular filling pressures are significantly correlated in
patients with advanced heart failure, there is a large distribution of the RAP/PCWP ratio. The
basis for the variability of this trait (RAP/PCWP ratio) is not well understood, nor is its
prognostic utility. In the ESCAPE trial which enrolled patients with advanced heart failure
selected for signs and symptoms of congestion, most of whom had elevated PCWPs, increasing
RAP/PCWP ratio resulted from increasing RAP. Subjects with a low RAP/PCWP ratio had
better right ventricular function as assessed by several echocardiographic measures (including
smaller right atrial and right ventricular area) and by the right ventricular stroke work index,
while those with a higher RAP/PCWP ratio had a higher pulmonary vascular resistance.
PCWP, qualitatataataaatti
usininnnnnng g g g g g g sisisisisisis x-x-x-x-xxx momomomomomomonnnntntnn h
v
p
venenenenenttt tt rate iiiin n n nn inininii crcrcrcrcreaeaeaeaeasisisisisingngngngng bbbbbasaasaa eelilililiinen RRRAPAPPPP/P/P/P/P/PCWCWCWCWCWP PP wawwww s 1616161616% %%%% (t(t(t(t(tererererertititititilellll
p=0=0=000.0.0.00.09.9.9.
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
10
Additionally, an elevated RAP/PCWP ratio was associated with a lower cardiac index and
impaired renal function at baseline and with a worse outcome at 6 months.
Whether the RAP/PCWP ratio is a stable and reproducible parameter in patients with
heart failure is not well known. In the CTRD, there was a significant correlation (r=0.33) of the
RAP/PCWP ratio when measured at least 1 day apart (median time 188 days).4 In the present
study, we confirmed this finding in patients with decompensated, advanced heart failure. In the
ESCAPE trial, the correlation between ratios of RAP/PCWP measured ~1.9 days apart was 0.49
(p<0.001). Additionally, there was relatively little shifting (11-12% of subjects) between tertiles
1 and 3 from baseline to final hemodynamic assessment. Together, these data suggest that the
RAP/PCWP ratio does, in part, reflect an underlying intrinsic trait in patients with advanced
heart failure.
The ratio RAP/PCWP can be influenced by changes in either the RAP or the PCWP. In
the ESCAPE trial, a high RAP/PCWP occurred on the basis of an elevated RAP rather than a
reduced PCWP (Table 3). In addition to a higher measured RAP, subjects in the highest tertile of
RAP/PCWP ratio also had clinical findings that provided confirmation of an elevated RAP
including more severe peripheral edema and ascites, and an elevated jugular venous pressure. In
contrast, in the CTRD, subjects in the highest quartile of RAP/PCWP ratio not only had the
highest RAP but they also had the lowest PCWP.4 This difference is likely due to the selection of
patients for the ESCAPE trial on the basis of signs and symptoms of congestion.
To our knowledge, only two prior studies have attempted to determine characteristics
associated with the relationship of the RAP to PCWP in patients with heart failure.4, 5 In a cohort
of patients with advanced heart failure undergoing cardiac transplant evaluation, female gender
was the only characteristic found to be associated with the RAP to PCWP relationship as
er, these data sususususususug
it inn pppppppatatatatatatatieieieieieeentntntntntntnts s s s s s s wiwiwwwww t
A rAPPPPP/P/P/P/P/PCWCWCWCWCWPP PPP cacacacacan nnnn bebebebbe iinfnfnfnfnflulululuuennnnncececececed dddd bybybybyby ccccchhhhananananangegegegegesssss ininininin eeeitititiitheheheheher rrrr thththththe eeee RARARARARAPPPPP ororooro
hihihighghgh RRRAPAPAP/P/P/PCWCWCWPPP ocococcucucurrrrrrededed ooonnn thththeee bababasisisisss ofofof aaannn elelelevevevatatatededed RRRAPAPAP
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
11
assessed by 4 categories based on whether the RAP was 10 mm Hg and PCWP 22 mm Hg.5
In the present study, female gender was not associated with RAP/PCWP ratio. Also in contrast to
the present study, renal dysfunction, PVR, cardiac index, and echocardiographic assessment of
RV dysfunction were not significantly different among the four hemodynamic profiles in the
prior study.5 We postulate that this difference is in part based on the analytic approach used; i.e.,
a hemodynamic classification based on dichotomous values of RAP and PCWP or via the
RAP/PCWP ratio. Nevertheless, both studies demonstrated significant variability in the
relationship of right and left ventricular filling pressures in patients with advanced heart failure.
In the CTRD, increasing quartile of RAP/PCWP was associated with younger age,
female gender, etiology of cardiomyopathy other than idiopathic or ischemic, increased number
of prior sternotomies, higher PVR, lower CI, and lower creatinine clearance.4 In the present
study, age was not associated with the RAP/PCWP ratio. This difference may be due to inclusion
of a broader range of patients in the CTRD (e.g., complex congenital heart disease) than in the
ESCAPE trial. In the ESCAPE database, the number of prior sternotomies was not captured. The
present study confirmed the association of increasing RAP/PCWP with declining renal function,
reduced cardiac index, and higher PVR first reported in the CTRD,4 indicating that these
associations warrant further discussion.
Increasingly, it is recognized that systemic venous congestion is an important contributor
to the cardiorenal syndrome.11, 12 In the ESCAPE trial, an elevated RAP previously was shown to
be weakly correlated with baseline renal function13 consistent with the findings of the present
study. Here we show that impaired renal function was prominent when right- and left-sided
ventricular filling pressures began to approximate one another. In such subjects, pericardial
constraint may lead to exaggerated diastolic ventricular interaction.14, 15 This pathophysiology
ssociated withhhh yyyyyyyo
or isisssssschchchchchchchememememememmicicicicicicic,,,,,,, inininininininc
s
a e
s,s,s, hhhhhigher rrr PVPVPVPVPVR,R,R,R,R llllloooowewewewewer r rrr CICICICICI, annnnnd dd loooweweeer r rr r crcrcrcrcreaeaeaeaeatititittinininiiinenenenene clelelelelearararararananananancecececece....4 IIIIIn
assococococociaiaiaiai tetetetetedd ddd wiwiwiwiwithththhh ttttthehehehe RRRRRAPAPAPAPAP/P/P/P/P/PCWCWCWCWCWPPPPP rarararratitititit oo.ooo TTTTThihihihihiss sss dididididiffffffffffeerererererencncncncnceeee mamamamamay yyyy bebbebb
fff papapatititienenentststs ininin ttthehehe CCCTRTRTRDDD (e(e(e( .g.g.gg.,, cccomomomplplplexexex cccononongegegeg nininitatatalll hehehearararttt dididiseseseaaa
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
12
may mediate the reduction in cardiac index associated with increasing RAP/PCWP ratio. A
disproportionately elevated RAP in relationship to the PCWP may therefore represent one
“hemodynamic signature” of patients with advanced systolic heart failure and cardiorenal
syndrome, and suggests that consideration of the right-left relationship may be important when
considering therapeutic strategies for treating congestion in heart.
The RAP/PCWP ratio also appears to have important relationships to the pulmonary
vasculature and the performance of the right ventricle. Increasing RAP/PCWP ratio was found to
be a marker for RV failure manifested by an enlarged right atrial area, enlarged right ventricular
area (both in systole and diastole) and a lower RV stroke work index. The RAP/PCWP ratio was
not associated with left ventricular volumes, ejection fraction, or severity of mitral regurgitation,
further emphasizing that this ratio reflected right ventricular performance. The hemodynamic
data also suggest that the RAP/PCWP ratio was related to changes in the pulmonary vasculature
because increasing RAP/PCWP ratio was associated with a higher PVR despite a similar PCWP
in each tertile. It is well known that there is variability in the increase of the pulmonary artery
pressure and PVR in response to an elevated PCWP in patients with heart failure. The basis of
this variability is not yet well understood16 but pulmonary hypertension is now being tested as a
therapeutic target in patients with heart failure.17 We hypothesize that an exaggerated response in
the pulmonary vasculature in response to an elevated PCWP (i.e., an increased PVR) is a
proximal pathophysiological event, leading to RV dysfunction and subsequently an increased
RAP/PCWP ratio. Studies with serial imaging and hemodynamic assessments are needed to test
this hypothesis.
Whether the ratio of RAP/PCWP is associated with outcome in patients with heart failure
has not previously been investigated to our knowledge. A high RAP/PCWP ratio was associated
ndex. The RAP/P/P/PP/PP P
seveveeeeeeririririririritytytytytytyty ofofofofofofof mmmmmmmiiiiititi r
a n
R a
thththththaaata this sss rararararatittt o o o oo rerererereflfflff ecececececteteteteted d d d d ririririr ghghghhht t veeenntririririricucucucuculallll r rrrr pepepep rfrfrfrfrforoooo mamamamamancncncncnce..e.e.e TTTTThehehehehe h
at ttttthehehehehe RRRRRAPAPAPAPAP/P/P/PPPCWCWCWCWCWP rarararr tititititio wawawawawasssss rerererer lalalallatetetetet ddd dd tototototo ccccchahahahahangngngngngesessss iiiiinnnnn thththththeee ee pupupupupulmlmlmmmononooo
RRRAPAPAP/P/P/PCWCWCWPPP rararatititiooo wawawasss asasassososociciciatatatededed wwwititithhh aaa hihihighghghgg ererer PPPVRVRVR dddesesespipipitetete aaa
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
13
with worse outcomes in patients with advanced heart failure who undergo LVAD implantation6
or transplantation.4 An elevated jugular venous pressure, consistent with a high RAP, has been
shown to be an independent risk factor for outcome in patients with NYHA class II-III heart
failure.18 In the ESCAPE trial (Table 4), a high baseline RAP to PCWP ratio was associated
with adverse events at 6 months as assessed by the primary outcome of the ESCAPE trial
(number of days alive outside the hospital) but not with crude mortality. A lack of association
with mortality may represent limited power given that a higher RAP/PCWP ratio was associated
with markers of RV dysfunction and with impaired renal function, both well known risk factors
for adverse outcomes in heart failure.19-22 The final RAP/PCWP was similarly associated with
the primary ESCAPE outcome. The association of increasing RAP/PCWP ratio with outcome
was more consistent in those with a PCWP 22 mm Hg, highlighting the importance of assessing
this ratio in patients whom have elevated left-sided ventricular filling pressures. Overall, these
findings reinforce the importance of RV function in patients with advanced heart failure.
Limitations
This was a retrospective analysis. The associations of RAP/PCWP with death and hospitalization
did not reach conventional levels of statistical significance in all models, perhaps because the
overall size of the cohort in ESCAPE who underwent right heart catheterization was relatively
small. As such, the prognostic utility of the RAP/PCWP ratio needs to be validated in other,
larger datasets.
was similarly y yyy asaaaaaa
AP/PCPCPCPCCCCWPWPWPWPWPWPWP rrrrrrratatatatatatatioioioioioioio w
t a
h t
t ininininin thoseeee wwwwwitiii h hh hh a a aaa PCPCPCPCPCWPWPWPWPWP 22222 2222 mmmmm HHg,g,g,g,g, hhhhhigigiggighlhlhlhh igigiggghththhh innnng g g g g thththththe eeee imimimimimpopopopoportrr a
whohohohohom mmmm hahahahhaveveveveve eleleleleleveveveevatttttededededed lllllefefefefeft-t-t-t-t-sisisisisidededededed dddd vevevevv ntntntntntririririricucucucuculalalalalar rrrr fffffilillilillil ngngngngg ppppprerrrr ssssssss urururuu eseseseses. ffffffff
hehehe iiimpmpmpororortatatancncnceee ofofof RRRVVV fufufuncncnctititiononon iiinnn papapap tititienenentststs wwwititithhhfff aaadvdvdvananancececeddd hehehearararttt
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
14
Conclusions
In patients with advanced heart failure selected for signs and symptoms of congestion, there was
a wide distribution in the ratio of RAP to PCWP. A high RAP/PCWP ratio was associated with a
high RAP, underlying RV dysfunction in the setting of an elevated pulmonary vascular
resistance, and was an adverse prognostic finding associated with impaired renal function and a
worse 6-month outcome.
Sources of Funding
Dr. Drazner is supported by the James M. Wooten Chair in Cardiology at UT Southwestern
Medical Center.
Disclosures
None.
References
1. Drazner MH, Hamilton MA, Fonarow G, Creaser J, Flavell C, Stevenson LW. Relationship between right and left-sided filling pressures in 1000 patients with advanced heart failure. J Heart Lung Transplant. 1999;18:1126-32. 2. Drazner MH, Prasad A, Ayers C, Markham DW, Hastings J, Bhella PS, Shibata S, Levine BD. The relationship of right- and left-sided filling pressures in patients with heart failure and a preserved ejection fraction. Circulation: Heart Fail. 2010;3:202-6. 3. Drazner MH, Hellkamp AS, Leier CV, Shah MR, Miller LW, Russell SD, Young JB, Califf RM, Nohria A. Value of clinician assessment of hemodynamics in advanced heart failure: the ESCAPE trial. Circulation: Heart Fail. 2008;1:170-7. 4. Drazner MH, Brown RN, Kaiser PA, Cabuay B, Lewis NP, Semigran MJ, Torre-Amione G, Naftel DC, Kirklin JK. Relationship of right- and left-sided filling pressures in patients with advanced heart failure: a 14-year multi-institutional analysis. The J Heart Lung Transplant. 2012;31:67-72. 5. Campbell P, Drazner MH, Kato M, Lakdawala N, Palardy M, Nohria A, Stevenson LW. Mismatch of right- and left-sided filling pressures in chronic heart failure. J Card Fail. 2011;17:561-8.
iology at UT SSSSSSSooooo
DiDiDiDiDiscscscscsclololololosusususuurerererr sssss
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
15
6. Kormos RL, Teuteberg JJ, Pagani FD, Russell SD, John R, Miller LW, Massey T, Milano CA, Moazami N, Sundareswaran KS, Farrar DJ. Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: incidence, risk factors, and effect on outcomes. J Thor Cardiovasc Surg. 2010;139:1316-24. 7. Binanay C, Califf RM, Hasselblad V, O'Connor CM, Shah MR, Sopko G, Stevenson LW, Francis GS, Leier CV, Miller LW. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA. 2005;294:1625-33. 8. Palardy M, Stevenson LW, Tasissa G, Hamilton MA, Bourge RC, Disalvo TG, Elkayam U, Hill JA, Reimold SC. Reduction in mitral regurgitation during therapy guided by measured filling pressures in the ESCAPE trial. Circulation: Heart Fail. 2009;2:181-8. 9. O'Meara E, Chong KS, Gardner RS, Jardine AG, Neilly JB, McDonagh TA. The Modification of Diet in Renal Disease (MDRD) equations provide valid estimations of glomerular filtration rates in patients with advanced heart failure. Eur J Heart Fail. 2006;8:63-7. 10. Tedford RJ, Hassoun PM, Mathai SC, Girgis RE, Russell SD, Thiemann DR, Cingolani OH, Mudd JO, Borlaug BA, Redfield MM, Lederer DJ, Kass DA. Pulmonary capillary wedge pressure augments right ventricular pulsatile loading. Circulation. 2012;125:289-97. 11. Tedford RJ, Hassoun PM, Mathai SC, Girgis RE, Russell SD, Thiemann DR, Cingolani OH, Mudd JO, Borlaug BA, Redfield MM, Lederer DJ, Kass DA. Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol. 2009;53:589-96. 12. Damman K, van Deursen VM, Navis G, Voors AA, van Veldhuisen DJ, Hillege HL. Increased central venous pressure is associated with impaired renal function and mortality in a broad spectrum of patients with cardiovascular disease. J Am Coll Cardiol. 2009;53:582-8. 13. Nohria A, Hasselblad V, Stebbins A, Pauly DF, Fonarow GC, Shah M, Yancy CW, Califf RM, Stevenson LW, Hill JA. Cardiorenal interactions: insights from the ESCAPE trial. J Am Coll Cardiol. 2008;51:1268-74. 14. Applegate RJ, Johnston WE, Vinten-Johansen J, Klopfenstein HS, Little WC. Restraining effect of intact pericardium during acute volume loading. Am J Physiol. 1992;262:H1725-33. 15. Atherton JJ, Moore TD, Lele SS, Thomson HL, Galbraith AJ, Belenkie I, Tyberg JV, Frenneaux MP. Diastolic ventricular interaction in chronic heart failure. Lancet. 1997;349:1720-4. 16. Guazzi M, Arena R. Pulmonary hypertension with left-sided heart disease. Nature Rev Cardiol. 2010;7:648-59. 17. Guazzi M, Vicenzi M, Arena R, Guazzi MD. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation. 2011;124:164-74. 18. Drazner MH, Rame JE, Stevenson LW, Dries DL. Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure. N Engl J Med. 2001;345:574-81. 19. Fonarow GC, Adams KF, Jr., Abraham WT, Yancy CW, Boscardin WJ. Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis. JAMA. 2005;293:572-80. 20. Di Salvo TG, Mathier M, Semigran MJ, Dec GW. Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol. 1995;25:1143-53.
SD, Thiemannnnnnnnn nnnnnA.AAAAAA IIIIIIImpmpmpmpmpmpmpororororororortatatatatatatancncncncncncncee ofofofofofofofensatattttttededededededd hhhhhheaeaeaeaeaeaeartrtrtrtrtrtrt fffffffaaiaia l
89-96. H
na 9asselblad V, Stebbins A, Paul DF, Fonarow GC, Shah M, Y, P51:1268-74
89-99-9-996.66.6.6 vavavavavan Deururururrseseesesen VMVMVMVMVM, NaNaNaNaNaviviviviv sssss G,G,G,G, VooVooorss AAAAAAAAAA, vavavavvan n n n VeVVVV lddldldldhuhuhuhuhuisiiii enenenenen DDDDDJ,JJJJ Hnononononousuuuu pressuruu e is aaasssociateteed wwithhh immmmmpapapapapairrreddd rennnalallll fffffunctctctctctiooonn annnd atitititiienenenenentstststs wwwwwititittth hh cacacaaardrdrdrrdioooovavavavv scscscss ulululullararararar dddddisisisii eaeaeaeaeaseseseee. J JJJJ AmAmAmAmAm CCCCColololoolll lll CaCaCaCaCardrdrdrdrdioioiii l.llll 22220000000000999asselblad V, Stebbbbbibibibibinsnsnsnsns AAAAA,, PaPaPaPaP uluu yy DFDFDFDFDF,,, FoFooonananan rororororow wwww GC, Shah M, Y,, HiHiHillllll JJJAAA. CCCararardididiorororenenenalalal iiintntnterereraaactctctioioionsnsns::: inininsisisighghghgg tststs fffrororommm thththeee ESESESCACACAPPP515151:1:1:12626268-8-8-88 7474747474
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
16
21. Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R, Arbustini E, Recusani F, Tavazzi L. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol. 2001;37:183-8. 22. O'Connor CM, Hasselblad V, Mehta RH, Tasissa G, Califf RM, Fiuzat M, Rogers JG, Leier CV, Stevenson LW. Triage after hospitalization with advanced heart failure: the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) risk model and discharge score. J Am Coll Cardiol. 2010;55:872-8.
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
17
Table 1. Relationship of the baseline to final RAP/PCWP tertile
Final RAP/PCWP tertile
T1 T2 T3
Baseline
RAP/PCWP
tertile
T1 27 (54%) 17 (34%) 6 (12%)
T2 16 (34%) 15 (32%) 16 (34%)
T3 5 (11%) 16 (35%) 25 (54%)
Data are presented as number (% of subjects within baseline RAP/PCWP tertile who were within
denoted final RAP/PCWP tertile).
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
18
Table 2. Baseline characteristics by baseline ratio of RAP to PCWP
Tertile RAP/PCWP P
1 2 3
N=63 N=62 N=63
Age, y 57 [47, 63] 58 [50, 66] 59 [48, 70] 0.14
Ethnicity: White 35 (56%) 39 (63%) 36 (57%) 0.7
Male 42 (67%) 48 (77%) 49 (78%) 0.16
Ischemic etiology 35 (56%) 31 (50%) 33 (52%) 0.7
Idiopathic etiology 21 (33%) 22 (36%) 23 (37%) 0.7
Hypertension 32 (51%) 28 (45%) 32 (51%) 1.000
Diabetes 14 (24%) 25 (40%) 22 (36%) 0.2
NYHA class IV 60 (95%) 54 (87%) 55 (87%) 0.1
JVP 8 cm 47 (77%) 59 (98%) 59 (97%) 0.0002
Ascites moderate 1 (2%) 11 (18%) 16 (25%) 0.0002
Peripheral edema 2+ 9 (14%) 28 (45%) 39 (62%) <.0001
Orthopnea 2 pillows 54 (86%) 50 (81%) 51 (82%) 0.6
Systolic blood pressure, mm Hg 111 [97, 120] 108 [98, 116] 109 [98, 120] 0.7
Heart rate, bpm 81 [71, 91] 79 [67, 91] 81 [69, 91] 0.8
Body mass index, kg/m2 25 [22, 30] 27 [24, 32] 29 [24, 35] 0.03
Creatinine, mg/dL 1.3 [0.9, 1.6] 1.5 [1.1, 1.8] 1.5 [1.2, 2] 0.004
CrCl, ml/min 62 [41, 91] 52 [44, 67] 52 [37, 68] 0.010
BUN, mg/dL 26 [16, 33] 33 [22, 51] 30 [22, 49] 0.003
2323 (3(3((((( 7%7%7%7%7%7%7%)))))))
32323232323232 (((((((51515151515151%)%%%%%%
)
)
47 (77%) 59 (98%) 59 (97 )
1414141414 (((2424242424%)%%%% 255555 (4(4(4(4(40%0%0%0%0%))) 2222222222 (((((3636363636%)%%%%
6060606060 (((995999 %)%)%)%)%) 55544444 (8(8(8(8(87%7%7%7%7%)))) 555 ((8787%%)
4747474747 (((((777777777 %)%)%)%)%) 55555999 (9(9(9(9(98%8%8%8%8%))))) 5959595959 (97%)
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
19
Table 3. Association of baseline RAP to PCWP ratio with invasively measured hemodynamics
Tertile RAP/PCWP P
1 2 3
Right atrial pressure, mm Hg 6 [4, 8] 13.5 [11, 17] 20 [13, 23] <.0001
Pulmonary capillary wedge pressure, mm Hg 23 [18, 30] 25 [22, 32] 24 [19, 30] 0.7
Pulmonary artery systolic, mm Hg 50 [40, 60] 58 [50, 70] 52 [42, 67] 0.08
Pulmonary artery diastolic, mm Hg 24 [18, 29] 29 [25, 36] 25 [20, 35] 0.02
Mean pulmonary artery pressure, mm Hg 42 [33, 49] 49 [42, 56] 45 [35, 57] 0.049
Transpulmonary gradient, mm Hg 9 [7, 12] 12 [8, 15] 13 [9, 17] 0.001
Pulmonary vascular resistance, WU 2.4 [1.8, 3.4] 2.9 [2, 4.1] 3.6 [2, 4.7] 0.003
Cardiac output, liters/min 3.9 [3, 4.5] 3.9 [3.2, 4.6] 3.3 [2.8, 4.9] 0.2
Cardiac index, liters/min/m2 2.1 [1.7, 2.3] 1.9 [1.7, 2.3] 1.8 [1.5, 2.2] 0.049
Mixed venous saturation, % 60 [44, 67] 54 [41, 62] 55 [44, 68] 0.45
Stroke volume, ml 47 [39, 56] 51 [41, 63] 44 [33, 60] 0.6
22222225555555 [2[2[2[2[2[2[22,2,2,2,2,2,2,
,
,
42 [33 49] 49 [42
5050505050 [[[[404044 , 6060000]]]]] 5858585858 [[[[[5050505050,
2424242424 [[[[[181111 ,, 2929292929]]]]] 29 [25,
444222 [3[3[3333 4449]9]9] 444999 [4[4[4222
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
20
Systemic vascular resistance, dyne-sec-cm-5 1387 [1042, 1664] 1310 [1089, 1596.5] 1322 [848, 1987] 0.9
Right ventricular stroke work index, g-m/m2 per beat 8.6 [6.9, 12] 8.4 [6.1, 11] 5.5 [4, 7.6] <.0001
Pulmonary arterial compliance, ml/mm Hg 1.83 [1.33, 2.58] 1.61 [1.3, 2.47] 1.65 [1.14, 2.27] 0.25
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
21
Table 4. Association of the RAP to PCWP ratio with death or hospitalization (days) at 6 months
Whole cohort* Subgroup PCWP 22 mm Hg*
Transplant/LVAD
count as dead
Transplant/LVAD
count as alive
Transplant/LVAD
count as dead
Transplant/LVAD
count as alive
HR (95% CI) P Value HR (95% CI) P value HR (95% CI) P Value HR (95% CI) P value
Baseline RAP/PCWP
Unadjusted 1.1 (0.97, 1.3) 0.14 1.12 (0.97, 1.3) 0.14 1.18 (1, 1.4) <0.05 1.2 (1.01, 1.4) 0.04
Adjusted
Model 1
1.13 (0.97, 1.3) 0.12 1.14 (0.99, 1.3) 0.08 1.18 (0.98, 1.4) 0.08 1.2 (1, 1.5) <0.05
Adjusted
Model 2
1.16 (1, 1.4) <0.05 1.19 (1.02, 1.4) 0.03 1.2 (1.02, 1.5) 0.03 1.3 (1.04, 1.5) 0.02
Final RAP/PCWP
Unadjusted 1.2 (1.1, 1.5) 0.001 1.3 (1.1, 1.5) 0.009 1.8 (1.2, 2.8) 0.009 1.8 (1.1, 2.7) 0.01
Adjusted 1.17 (0.99, 1.3) 0.07 1.17 (0.99, 1.4) 0.07 1.8 (1.1, 3.1) 0.03 1.8 (1.05, 3.1) 0.03
PP
2
4 1.12 0.97, 1. 0.14 1.18 1, 1.
2
4 1.111 1212121212 (((((0.0.0.0.0.9797979797, 1.1.1.1.1.3)3)33 00000.1.11114 4444 1.1.1.1.1.1818181818 (((((1,1,1,1,1, 11111.
1.14 (0.9999999 ,,,,, 1.1.1.1.1.3)3)3)3)3) 00000.0.0.0.08888 1.18 (0.98,
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
22
Model 1
Adjusted
Model 2
1.19 (.99, 1.4) 0.06 1.19 (0.99, 1.4) 0.06 1.7 (1.01, 3) 0.04 1.7 (0.99, 3) 0.05
*Whole cohort: N=183 for baseline RAP/PCWP; N=137 for final RAP/PCWP; Subgroup PCWP 22 mm Hg: N=137 for baseline
RAP/PCWP; N=35 for final RAP/PCWP.
Model 1 adjusted for six minute walk, BUN, Systolic blood pressure.
Model 2 adjusted for six minute walk, BUN, systolic blood pressure, PCWP.
Hazard ratios in whole cohort shown are for unit ratio change (1 standard deviation) baseline RAP/PCWP=0.235; for final
RAP/PCWP=0.306. Hazard ratios for subgroup PCWP 22 mm Hg are for unit ratio change (1 standard deviation) baseline
RAP/PCWP 0.235; for final RAP/PCWP 0.20.
u e
u
0
unununnunitiiii r ttatttioioioioo cccchahahahahangngngngngeeeee (1(1(1(1(1 statatatt ndddardrdrdrdrd dddddeveveveveviaiaiaaatitititit onnnnn) )))) bababababaseseseseselililililinennnn
up PPPPPCWCWCWCC P 222222 mmmm HgHgHgHgHg aaarererere fffffororororo uniiiinit ratio hchhange
000
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
23
Figure Legends
Figure 1. The distribution of the RAP/PCWP ratio in the study cohort. RAP = right atrial
pressure; PCWP = pulmonary capillary wedge pressure
Figure 2. Association of echocardiographic measures of right ventricular dysfunction with
RAP/PCWP ratio (tertiles).
A. Right atrial area
B. Right ventricular area (diastole)
C. Right ventricular area (systole)
D. Inferior vena cava size (expiration)
E. Inferior vena cava size (inspiration).
Data are presented as box-and-whisker plots.
RAP/PCWP ratios were Tertile 1 (T1): 0.27-0.4; Tertile 2 (T2): 0.41-0.61; Tertile 3 (T3): 0.62 –
1.21.
*P<0.005 † P<0.01
area (systole)
a
as box and whisker plots
arererererea a aaa (s(s(s(ssysysysysy tooooolellll )
aaa aa ssisss ze (expippirratttioon)))))
a size (inspiration)n)n)n).
aass bobobox-x-anand-d-d-dd whwhwhhhisisisii kekekek rr plplplottottss
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from
Joseph D. Mishkin, Pradeep P.A. Mammen, David W. Markham and Chetan B. PatelMark H. Drazner, Mariella Velez-Martinez, Colby Ayers, Sharon C. Reimold, Jennifer T. Thibodeau,
from the ESCAPE TrialRelationship of Right- to Left-Ventricular Filling Pressures in Advanced Heart Failure: Insights
Print ISSN: 1941-3289. Online ISSN: 1941-3297 Copyright © 2013 American Heart Association, Inc. All rights reserved.
is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation: Heart Failure published online February 7, 2013;Circ Heart Fail.
http://circheartfailure.ahajournals.org/content/early/2013/02/07/CIRCHEARTFAILURE.112.000204World Wide Web at:
The online version of this article, along with updated information and services, is located on the
http://circheartfailure.ahajournals.org//subscriptions/
is online at: Circulation: Heart Failure Information about subscribing to Subscriptions:
http://www.lww.com/reprints Information about reprints can be found online at: Reprints:
document. Permissions and Rights Question and Answer process is available in the
click Request Permissions in the middle column of the Web page under Services. Further information about thisEditorial Office. Once the online version of the published article for which permission is being requested is located,
can be obtained via RightsLink, a service of the Copyright Clearance Center, not theCirculation: Heart Failure Requests for permissions to reproduce figures, tables, or portions of articles originally published inPermissions:
by guest on July 15, 2018http://circheartfailure.ahajournals.org/
Dow
nloaded from