Download Pulmonary Hypertension, Right Ventricular Function, and Clinical

Journal of Cardiac Failure Vol. 19 No. 10 2013
Clinical Investigations
Pulmonary Hypertension, Right Ventricular Function,
and Clinical Outcome in Acute Decompensated Heart Failure
DORON ARONSON, MD,1 WISAM DARAWSHA, MD,1 AULA ATAMNA,1 MARIELLE KAPLAN, PhD,2
BADIRA F. MAKHOUL, MD,3 DIAB MUTLAK, MD,1 JONATHAN LESSICK, MD,1 SHEMY CARASSO, MD,1
SHIMON REISNER, MD,1 YORAM AGMON, MD,1 ROBERT DRAGU, MD,1 AND ZAHER S. AZZAM, MD3
Haifa, Israel
ABSTRACT
Background: Pulmonary hypertension (PH) and right ventricular (RV) dysfunction have been associated
with adverse outcome in patients with chronic heart failure. However, data are lacking in the setting of
acute decompensated heart failure (ADHF). We sought to determine prognostic significance of PH in patients with ADHF and its interaction with RV function.
Methods: We studied 326 patients with ADHF. Pulmonary artery systolic pressure (PASP) and RV function were determined with the use of Doppler echocardiography, with PH defined as PASP O50 mm Hg.
The primary end point was all-cause mortality during 1-year follow-up.
Results: PH was present in 139 patients (42.6%) and RV dysfunction in 83 (25.5%). The majority of
patients (70%) with RV dysfunction had PH. Compared with patients with normal RV function and without PH, the adjusted hazard ratio (HR) for mortality was 2.41 (95% confidence interval [CI] 1.44e4.03;
P 5 .001) in patients with both RV dysfunction and PH. Patients with normal RV function and PH had an
intermediate risk (adjusted HR 1.78, 95% CI 1.11e2.86; P 5 .016). Notably, patients with RV dysfunction
without PH were not at increased risk for 1-year mortality (HR 1.04, 95% CI 0.43e2.41; P 5 .94). PH
and RV function data resulted in a net reclassification improvement of 22.25% (95% CI 7.2%e37.8%;
P 5 .004).
Conclusions: PH and RV function provide incremental prognostic information in ADHF. The combination of PH and RV dysfunction is particularly ominous. Thus, the estimation of PASP may be warranted in
the standard assessment of ADHF. (J Cardiac Fail 2013;19:665e671)
Key Words: Acute heart failure, prognosis, pulmonary hypertension, right ventricle.
Pulmonary hypertension (PH) is a common complication
of chronic heart failure (HF).1 In patients with left ventricular
systolic dysfunction, elevated pulmonary artery pressure predicts higher risk for morbidity and mortality.2 Furthermore,
increased pulmonary pressures are associated with reduced
exercise capacity3 and contribute to dyspnea on exertion.
In acute decompensated heart failure (ADHF), increased pulmonary arterial pressure correlates with dyspnea at rest.4
Echocardiographic estimation of pulmonary artery systolic pressure (PASP) can be used as a surrogate to diagnose
the presence and severity of PH. Following the results of
the ESCAPE (Evaluation Study of Congestive Heart Failure
and Pulmonary Artery Catheterization Effectiveness) trial,5
Doppler echocardiography is used with increasing frequency to diagnose PH in patients with HF. However, the
reliability of Doppler echocardiography to accurately
From the 1Department of Cardiology, Rambam Medical Center; and the
Ruth and Bruce Rappaport Faculty of Medicine, TechnioneIsrael Institute
of Technology, Haifa, Israel; 2Laboratory of Clinical Biochemistry, Rambam Medical Center; and the Ruth and Bruce Rappaport Faculty of Medicine, TechnioneIsrael Institute of Technology, Haifa, Israel and
3
Department of Internal Medicine B, Rambam Medical Center; and the
Ruth and Bruce Rappaport Faculty of Medicine, TechnioneIsrael Institute
of Technology, Haifa, Israel.
Manuscript received July 11, 2013; revised manuscript received August
17, 2013; revised manuscript accepted August 22, 2013.
Reprint requests: Doron Aronson, MD, Department of Cardiology, Rambam Medical Center, Bat Galim, POB 9602, Haifa 31096, Israel. Tel: 97248-542790; Fax: 972-48-542176. E-mail: [email protected]
See page 670 for disclosure information.
1071-9164/$ - see front matter
Ó 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.cardfail.2013.08.007
665
666 Journal of Cardiac Failure Vol. 19 No. 10 October 2013
estimate pulmonary pressures has been recently questioned
in various patient populations.6,7
Previous studies have shown that echocardiographic diagnosis of elevated PASP in stable outpatient HF patients
is associated with increased risk,8,9 whereas studies in the
setting of ADHF have used invasive hemodynamic measurements.10 Furthermore, it is not known whether PASP
remains an independent predictor of mortality when newer
risk variables, such as elevated brain natriuretic peptide
(BNP),11 elevated cardiac troponin levels,12 or red cell distribution width,13 are considered.
The right ventricle (RV) can accommodate large changes
in volume loading but has a limited contractile reserve to
match increased afterload.14 A progressive increase in
afterload is a major cause of RV adaptation and, ultimately,
failure. The ability of the RV to adapt to an increase in pulmonary pressures may therefore be an important determinate of clinical outcome as recently demonstrated in
stable heart failure.15
Despite the importance of PH in ADHF, and the inextricable relationship of RV function with the pulmonary circulation, earlier studies in ADHF have only analyzed the
impact of PH in isolation. Therefore, we sought to study
the prognostic implications of PH in combination with
RV function in patients admitted for ADHF.
estimated PASP, RV function, and left ventricular function was
carried out by one of 5 experienced noninvasive cardiologists
(Y.A., D.M., J.L., D.A., and S.R.) without knowledge of the patient
outcome.
Echocardiograms were performed in multiple views to obtain
the optimal appearing tricuspid regurgitation jet. The estimated
PASP was calculated as the sum of the peak systolic pressure gradient across the tricuspid valve (approximated by the modified
Bernoulli equation) and the right atrial pressure.18 Right atrial
pressure was estimated according to the size and respiratory variation of the inferior vena cava diameter in the subcostal view with
the use of established criteria.18 In keeping with current guidelines, PH was defined using the cutoff of PASP O50 mm Hg.19,20
Right ventricular (RV) systolic function and RV size were qualitatively estimated by visual assessment as previously described.21
In addition, we calculated the RV fractional area change
(RVFAC), as the difference in RV diastolic and systolic areas, divided by the diastolic area, in the apical 4-chamber view, with
RVFAC !35% defined as abnormal.18 RV dysfunction was considered to be present if at least mild systolic dysfunction was observed. Each echocardiogram was reviewed independently by 2
physicians for RV function. In case of disagreement, a 3rd physician reviewed the study and the majority rule was applied. The
agreement in the assessment or RV function between echocardiogram readers was high (Cohen kappa 0.82, 95% confidence interval [CI] 0.67e0.97).
Methods
The primary end point of the study was all-cause mortality after
hospital discharge. After hospital discharge, clinical end point information was acquired by reviewing the national death registry
and by reviewing the hospital records for major clinical events
if the patient had been rehospitalized.
From January 2008 to April 2011, all patients admitted to the
Rambam Medical Center, Haifa, Israel, with the primary diagnosis
of ADHF entered a prospective registry. Eligible patients were
those hospitalized with new-onset or worsening of preexisting heart
failure as the primary cause of admission, or those with significant
heart failure symptoms that developed during the hospitalization
where heart failure was the primary discharge diagnosis.16
ADHF was diagnosed according to the European Society of Cardiology criteria, including a B-type natriuretic peptide (BNP) level
O400 pg/mL.17 BNP levels were measured with the Axsym
BNP microparticle enzyme immunoassay (Abbott Laboratories,
Abbott Park, Illinois). The study was conducted in accordance
with the principles of the Declaration of Helsinki and approved
by the Institutional Review Committee on Human Research.
The degree of congestion at admission was evaluated based on
a combination of several signs and symptoms. A 10-point scale
ranging from 0 to 9 was constructed as follows: orthopnea
(1 point), raised JVP (n 5 1), hepatomegaly (n 5 1), chest radiograph showing pulmonary venous congestion, interstitial edema,
or alveolar edema (n 5 1), chest radiograph showing pleural effusion (n 5 1), presence of peripheral edema (absent/trace, 0 points;
slight, 1 point; moderate, 2 points; marked, 3 points; and anasarca,
4 points). A composite congestion score was calculated by summing the individual scores. The latter was divided into 0e1,
2e3, 4e5, or $6 signs of congestion.
For the present analysis we excluded patients in which tricuspid
regurgitation jets were not analyzable.
Echocardiographic Evaluation
All echocardiographic studies were performed during hospital
stay by an experienced certified sonographer. Analysis of
Study End Point
Statistical Analysis
Continuous variables are presented as mean (SD) or median (interquartile range) and categoric variables as n (%). The baseline
characteristics of the groups were compared with the use of analysis of variance for continuous variables and c2 statistic for categoric variables.
The distribution of BNP was skewed. Therefore, logarithmically transformed values of BNP (ln BNP) were used. The association between BNP and clinical characteristics, biochemical
variables, and echocardiographic data (including PASP and RV
function) was assessed by univariable linear regression of ln
BNP on each variable separately followed by multiple linear regression with backward selection. In addition to age and sex
(which were forced into the model) baseline variables considered
for inclusion in the multivariable model included: body mass index (BMI), history of hypertension, history of diabetes, atrial fibrillation, estimated glomerular filtration rate (eGFR), blood
urea nitrogen (BUN), serum sodium, baseline hemoglobin, red
cell distribution width (RDW), left ventricular ejection fraction
(LVEF), RV function, and PASP.
Survival curves were constructed for the PH/RV function categories with the use of the Kaplan-Meier method and were
compared with the use of the log-rank test. Stepwise Cox proportional hazards models with backward selection were used to
calculate hazard ratios (HRs) and 95% CIs for the PH/RV function
categories. The Cox models were adjusted for age, sex, BMI, history of diabetes, hypertension, eGFR, blood urea nitrogen (BUN),
Pulmonary Hypertension and RV Function in ADHF
hemoglobin, serum sodium, atrial fibrillation, elevated cardiac troponin I, BNP levels, LVEF, and medical therapies (beta-blockers,
angiotensin-converting enzyme inhibitors, loop diuretics, spironolactone, and digoxin).
The reclassification of 1-year mortality risk was evaluated by
comparing predicted risk estimates based on multivariable models
with and without the PH/RV function data.22 The net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) were calculated by summing the reclassification
improvements for those who died during follow-up and for those
who survived. For the later analysis, the predicted 1-year mortality
probabilities were determined with a logistic regression and
ranked into quartiles, thus creating 4 risk categories (!20%,
20%e30%, 30%e48% and O48%).
Differences were considered to be statistically significant at the
2-sided P ! .05 level. Statistical analyses were performed with
the use of Stata version 12.0 (College Station, Texas).
Results
During the study period, 395 patients who met the inclusion criteria were recruited. Of these, PASP could be
estimated in 326 patients (83%). Compared with patients
with available PASP data, patients with missing PASP
data (n 5 69) were younger (71 6 11 vs 75 6 11 years;
P 5 .004) and had higher eGFR (56 6 23 vs 50 6 23
mL min 1 1.73 m 2, P 5 .04). They were similar regarding sex, sodium levels, RDW, BNP levels, prevalence of
hypertension, diabetes, atrial fibrillation, LVEF, and RV
function. Mortality after hospital discharge was similar
among patients with and without missing PASP (logrank: P 5 .95).
In the 326 patients with estimatable PASP, PH was present in 139 patients (42.6%) and RV dysfunction in 83 patients (25.5%). The majority of patients with RV
dysfunction had PH (n 5 59; 70.1%). Demographic and
clinical characteristics of the patients according to PASP/
RV classification are presented in Table 1. Patients with
RV dysfunction were younger and presented with higher
RDW. Among the liver function tests, g-glutamyl transferase was significantly higher in patients with both PH and
RV dysfunction. They were more likely to have reduced
left ventricular systolic function, higher BNP levels, and
to be treated with beta-blockers and spironolactone.
Table 2 depicts clinical and laboratory parameters that
were independently associated with BNP levels. When considered as a continuous variable, PASP was a significant
predictor of BNP levels, after adjustments for LVEF and
other factors known to be associated with BNP. When considered as a categoric variable, RV dysfunction also was independently associated with higher BNP levels.
One or more signs of congestion were present in 281
patients (16%). Figure 1 shows the relationship between
RV function/PH categories and the number of signs of congestion. Signs and symptoms of congestion were more frequently present in patients with RV dysfunction,
particularly when PH was also present.
Aronson et al
667
Effects of PASP and RV Function on Mortality
During the 1-year follow-up period, 112 patients (34.4%)
died. The Kaplan-Meier survival curves of the 4 study subgroups are shown in Figure 2. Patients with normal RV
function and without PH had the lowest 1-year mortality.
There was a marked increase in the risk of mortality in patients with both RV dysfunction and PH, and patients with
normal RV function and PH had an intermediate risk. Notably, patients with RV dysfunction but without PH were
not at increased risk for 1-year mortality. Other univariable
predictors of 1-year mortality included age, female sex,
baseline hemoglobin, BUN, elevated troponin, RDW,
BNP, and the congestion score.
Similar results were obtained after adjustments for other
risk variables in a multivariable Cox regression model
(Table 3), again indicating that RV dysfunction was associated with increased mortality risk only in the presence of
concomitant PH. Using PASP as a continuous variable in
the same Cox model, the adjusted HR for a 10 mm Hg increase in PASP was 1.20 (95% CI 1.08e1.34; P 5 .001).
Other independent predictors of mortality included age,
female sex, BUN, elevated troponin, RDW, and the congestion score, whereas baseline hemoglobin and ln BNP did
not remain independently associated with mortality.
Figure 3 demonstrates that estimated PASP offered an improvement in reclassification of 1-year mortality risk. The
net reclassification improvement, which indicates the overall reclassification in the desirable direction, was 22.5%
(95% CI 7.2%e37.8%; P 5 .004). Reclassification occurred predominately in the intermediate-risk groups. The
IDI gain was of 2.9% (95% CI 0.9e5.9%; P 5 .004).
Discussion
This study shows that PH as assessed by Doppler echocardiography is present in O40% of patients with ADHF.
PH was a powerful predictor of 1-year mortality independently from several novel risk factors, such as RDW,
BNP, and troponin levels, in patients with both normal
RV function and RV dysfunction. PH was strongly associated with RV dysfunction and was a major determinant of
mortality in this subgroup.
Furthermore, the relationship between PH and RV function and mortality was not attenuated by adjustments for
other variables. When mortality risk reclassification was
evaluated, the differences in NRI offered by the combined
assessment of PH and RV function were clinically meaningful, indicating that these variables provide fundamental
hemodynamic information representing disease severity
rather than reflecting other comorbidities.
Despite the presence of several other factors that affect
BNP levels, both increased PASP and RV dysfunction
were independently associated with higher BNP levels.
These results indicate that in ADHF, the release of BNP is
also triggered by the increased pressure and volume stress
on the RV. The hemodynamic consequences of the
668 Journal of Cardiac Failure Vol. 19 No. 10 October 2013
Table 1. Baseline Clinical Characteristics According to PH-RV Function Category
Characteristic
Age (y)
Female gender
Hypertension
BMI
Diabetes mellitus
Chronic lung disease
Coronary artery disease
Creatinine (mg/dL)
eGFR (mL min 1 1.73 m 2)
BUN (mg/dL)
Serum sodium (mmole/L)
Aspartate transaminase (IU/L)
Alanine transaminase (IU/L)
g-Glutamyl transferase (IU/L)
Alkaline phosphatase (IU/L)
Hemoglobin (g/dL)
Hematocrit (%)
Red cell distribution width (%)
BNP (ng/mL)
Troponin elevation (%)
Atrial fibrillation
Chronic lung disease
LVEF !45%
PASP (mm Hg)
Estimated right atrial pressure
(mm Hg)
Medications
Beta-blockers
ACE inhibitors/ARBs
Spironolactone
Digoxin
Loop diuretics
Normal PASP/RV
Function (n 5 163)
Elevated PASP/Normal
RV (n 5 80)
Normal PASP/RV
Dysfunction (n 5 24)
Elevated PASP/RV
Dysfunction (n 5 59)
P Value
77 6 11
98 (60)
132 (81)
28.0 6 4.7
67 (41)
25 (15)
90 (55)
1.5 6 0.8
52 6 24
30 6 19
137 6 6
24 [19e37]
34 [27e47]
50 [32e98]
94 [73e126]
11.7 6 2.0
35 6 6
15.3 6 1.9
956 [668e1606]
17 (10)
71 (44)
25 (15)
67 (41)
40 6 8
7.0 6 3.7
78 6 9
47 (59)
70 (88)
29.8 6 6.8
39 (49)
15 (19%)
43 (54)
1.7 6 0.9
46 6 21
32 6 17
136 6 4
23 [18e31]
30 [23e38]
42 [28e103]
91 [70e119]
11.2 6 1.9
34 6 5
15.9 6 1.7
1113 [646e1649]
13 (16)
35 (44)
15 (19)
39 (49)
64 6 10
10.9 6 5.1
71 6 15
11 (46)
16 (675)
27.9 6 7.2
13 (54)
2 (8%)
16 (67)
1.4 6 0.4
57 6 19
30 6 14
137 6 3
32 [20e57]
39 [29e72]
48 [32e153]
85 [70e108]
12.1 6 2.1
37 6 6
15.2 6 1.5
1728 [641e3235]
4 (17)
6 (25)
2 (8)
18 (75)
42 6 7
11.9 6 4.3
70 6 14
26 (44)
45 (76)
30.7 6 12.3
30 (51)
13 (22)
35 (59)
1.7 6 0.8
47 6 21
36 6 23
137 6 4
23 [19e33]
29 [19e50]
101 [50e186]
103 [78e135]
11.8 6 1.8
36 6 6
16.2 6 1.4
1551 [787e2717]
7 (12)
24 (41)
13 (22)
34 (57)
66 6 14
15.0 6 6.0
!.0001
.12
.10
.32
.39
.42
.67
.13
.15
.25
.54
.10
.005
!.0001
.25
.12
.10
.001
.002
.56
.37
.42
.006
.001
!.0001
104
101
21
11
137
(64)
(62)
(13)
(7)
(84)
57
50
12
5
68
(71)
(63)
(15)
(6)
(85)
17
18
7
5
68
(71)
(75)
(29)
(21)
(85)
48
41
22
8
57
(81)
(70)
(37)
(14)
(97)
.09
.50
!.0001
.06
.08
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BNP, B-type natriuretic peptide; LVEF, left ventricular ejection fraction; PASP,
pulmonary arterial systolic pressure.
Values are presented as n (%) of patients, mean 6 SD, or median [interquartile range].
combination of RV dysfunction and PH were also evident by
the more severe profile of signs and symptoms of
congestion.
PH as diagnosed by Doppler-derived estimated PASP is
highly prevalent among patients with chronic HF8,23 and
following acute myocardial infarction.24 Hemodynamic
worsening that includes increasing pulmonary arterial pressure is characteristic of ADHF.25 However, few data are
available in the setting of ADHF,10 and RV function was
not taken into consideration.
Mean pulmonary artery pressure mirrors left-sided filling
pressure owing to backward pressure transmission.
Therefore, increased estimated PASP integrates the combined severity of the adverse hemodynamic alterations,
such as systolic and diastolic dysfunction or mitral valve regurgitation.9,24,26 When the pulmonary circulation is subject to persistent and excessive elevation in venous
pressures, several maladaptive process may ensue, resulting
in vasoconstriction and pulmonary arterial remodeling, and
eventually leading to a superimposed precapillary component of PH.1,10
Left ventricular systolic impairment is thought to be the
most common cause of RV dysfunction. The failing left
ventricle may promote RV dysfunction through several
Table 2. Multivariable Linear Regression Analysis With ln BNP as the Dependent Variable
Unadjusted
Independent Variable
BMI (per 1 kg/m2 increase)
LVEF (per 10% decrease)
eGFR (per 10 mL/min decrease)
RV dysfunction
ln PASP
Hemoglobin (per 1 g/dL increase)
Regression Coefficient (SE)
0.02
0.19
0.07
0.35
0.11
0.03
(0.01)
(0.03)
(0.02)
(0.08)
(0.04)
(0.02)
Adjusted
P Value
.001
!.0001
!.0001
!.0001
.001
.08
Regression Coefficient (SE)
0.03
0.17
0.06
0.18
0.08
0.04
(0.01)
(0.03)
(0.02)
(0.09)
(0.04)
(0.02)
BMI, body mass index; eGFR, estimated glomerular filtration rate; RV, right ventricular; other abbreviations as in Table 1.
The model was also adjusted for age and sex.
P Value
.0004
!.0001
.0002
.038
.02
.037
Pulmonary Hypertension and RV Function in ADHF
Aronson et al
669
Fig. 2. Kaplan-Meier survival plot of mortality in subgroups defined by pulmonary hypertension and right ventricular function.
Abbreviations as in Figure 1.
Fig. 1. Relationship between right ventricular (RV) function/pulmonary hypertension (PH) categories and number of signs and
symptoms of congestion.
mechanisms. These include ventricular interdependence associated with septal dysfunction and limited pericardial
flexibility in the presence of left ventricular dilation, neurohormonal activation due to concomitant left ventricular
dysfunction, shared cardiomyopathic process, and ischemic
RV injury.14,27
The RV can accommodate large changes in volume loading, but has a limited contractile reserve to match increased
impedance to ejection. Therefore, compared with the left
ventricle, the RV demonstrates a heightened sensitivity to
afterload change.14 Thus, regardless of the initial mechanism for RV dysfunction, an increase in RV afterload
through the development of pulmonary arterial
hypertension secondary to increased left-sided filling pressures promotes RV remodeling and failure.14
In the present study, the profound effect of PH on the RV
translated into major differences in mortality. Although PH
was associated with increased mortality in patients with
normal RV function, there was a striking increase in mortality in patients with both PH and RV dysfunction. In contrast, RV dysfunction without PH did not incur increased
mortality risk. This finding is consistent with studies in stable heart failure,15 and suggests that the dysfunctional RV
can compensate in the absence of pressure overload.
Study Limitations
The present study has some limitations that merit emphasis. No data were available on the severity of chronic obstructive pulmonary disease. However, the frequency of
chronic lung disease was not associated with PASP in this
study, as in previous studies of patients with HF.9,23 In addition, data are lacking regarding specific conditions that
Table 3. Unadjusted and Adjusted Cox Proportional Hazards Model for All-Cause Mortality
Unadjusted
Characteristic
PH/RV function category
Normal RV/No PH
Normal RV/PH
RVD/No PH
RVD/PH
Age (per 10 y)
Female sex
Hemoglobin (per 1 gr/dL decrease)
BUN (per 10 mg/dL increase)
Elevated troponin
RDW (per 1% increase)
ln BNP*
Congestion score (per 1 sign)
HR (95% CI)
1.0
1.80
0.97
2.49
1.16
0.56
1.13
1.19
2.56
1.17
1.37
1.13
(reference)
(1.14e2.82)
(0.41e2.27)
(1.56e3.98)
(0.98e1.38)
(0.39e0.82)
(1.02e1.24)
(1.09e1.29)
(1.64e3.99)
(1.06e1.29)
(1.14e1.64)
(1.03e1.23)
Adjusted
P Value
d
.01
.97
.0001
.09
.003
.02
!.0001
!.0001
.002
.008
.007
HR (95% CI)
1.0
1.78
1.04
2.41
1.29
0.64
1.13
2.92
1.13
1.12
(reference)
(1.11e2.86)
(0.43e2.47)
(1.44e4.03)
(1.07e1.56)
(0.43e0.95)
d
(1.02e1.24)
(1.80e4.75)
(1.01e1.25)
d
(1.02e1.24)
BUN, blood urea nitrogen; CI, confidence interval; HR, hazard ratio; RDW, red cell distribution width; RVD, right ventricular dysfunction.
*HR for BNP is for 1-SD increase.
P Value
d
.016
.94
.001
.009
.028
d
.015
!.0001
.029
d
.02
670 Journal of Cardiac Failure Vol. 19 No. 10 October 2013
A
echocardiographic assessment of RV function remains inherently problematic.18
Conclusion
PH, as assessed by echocardiography, is a common finding in ADHF and is frequently associated with RV dysfunction. PH and RV function provide incremental prognostic
information independently from other established predictors of outcome. The combination of PH and RV dysfunction is particularly ominous. Therefore, the estimation of
PASP may be warranted in the standard assessment of
ADHF patients and is especially important in the presence
of RV dysfunction.
Disclosures
B
None.
References
Fig. 3. Net reclassification improvement based on addition of PH
and RV dysfunction (RVD) to standard risk factors for mortality in
patients (A) with and (B) without events. Individuals in the central
diagonal boxes (blue shading) did not change classification with
the addition of estimated PASP. Green shading (upper right boxes)
indicates the individuals who were reclassified in a desirable direction when estimated PH and RV function were added to the
baseline model; red shading (lower right boxes) indicates individuals who were reclassified in an undesirable direction. Abbreviations as in Figure 1.
might have contributed to the development of reactive PH,
such as pulmonary embolism and sleep disordered breathing. Notwithstanding, the clinical profile of our study population is characteristic of patients with PH secondary to
elevated left-sided filling pressures rather than patients
with pulmonary arterial hypertension.28 The absence of
signs of congestion in a small proportion of patients
may limit the extrapolation of the study results to other
HF populations. Finally, analysis of RV function is
complicated by the complex asymmetric geometry and
insufficient endocardial border delineation. Therefore,
1. Georgiopoulou VV, Kalogeropoulos AP, Borlaug BA, Gheorghiade M,
Butler J. Left ventricular dysfunction with pulmonary hypertension:
part 1: epidemiology, pathophysiology, and definitions. Circ Heart
Fail 2013;6:344e54.
2. Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R,
et al. 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;37:183e8.
3. Butler J, Chomsky DB, Wilson JR. Pulmonary hypertension and exercise intolerance in patients with heart failure. J Am Coll Cardiol 1999;
34:1802e6.
4. Solomonica A, Burger AJ, Aronson D. Hemodynamic determinants of
dyspnea improvement in acute decompensated heart failure. Circ
Heart Fail 2013;6:53e60.
5. Binanay C, Califf RM, Hasselblad V, O’Connor CM, Shah MR,
Sopko G, et al. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial.
JAMA 2005;294:1625e33.
6. Fisher MR, Forfia PR, Chamera E, Housten-Harris T, Champion HC,
Girgis RE, et al. Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension. Am J Respir Crit
Care Med 2009;179:615e21.
7. Rich JD, Shah SJ, Swamy RS, Kamp A, Rich S. Inaccuracy of Doppler echocardiographic estimates of pulmonary artery pressures in patients with pulmonary hypertension: implications for clinical
practice. Chest 2011;139:988e93.
8. Lam CS, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT,
Redfield MM. Pulmonary hypertension in heart failure with preserved
ejection fraction: a community-based study. J Am Coll Cardiol 2009;
53:1119e26.
9. Damy T, Goode KM, Kallvikbacka-Bennett A, Lewinter C, Hobkirk J,
Nikitin NP, et al. Determinants and prognostic value of pulmonary arterial pressure in patients with chronic heart failure. Eur Heart J 2010;
31:2280e90.
10. Aronson D, Eitan A, Dragu R, Burger AJ. Relationship between reactive pulmonary hypertension and mortality in patients with acute decompensated heart failure. Circ Heart Fail 2011;4:644e50.
11. Fonarow GC, Peacock WF, Phillips CO, Givertz MM, Lopatin M. Admission B-type natriuretic peptide levels and in-hospital mortality in
acute decompensated heart failure. J Am Coll Cardiol 2007;49:
1943e50.
Pulmonary Hypertension and RV Function in ADHF
12. Peacock WFT, de Marco T, Fonarow GC, Diercks D, Wynne J,
Apple FS, Wu AH, Adhere Investigators. Cardiac troponin and
outcome in acute heart failure. N Engl J Med 2008;358:2117e26.
13. Makhoul BF, Khourieh A, Kaplan M, Bahouth F, Aronson D, Azzam ZS.
Relation between changes in red cell distribution width and clinical outcomes in acute decompensated heart failure. Int J Cardiol 2013;167:
1412e6.
14. Haddad F, Doyle R, Murphy DJ, Hunt SA. Right ventricular function in
cardiovascular disease, part II: pathophysiology, clinical importance,
and management of right ventricular failure. Circulation 2008;117:
1717e31.
15. Ghio S, Temporelli PL, Klersy C, Simioniuc A, Girardi B, Scelsi L,
et al. Prognostic relevance of a noninvasive evaluation of right ventricular function and pulmonary artery pressure in patients with chronic
heart failure. Eur J Heart Fail 2013;15:408e14.
16. Fonarow GC, Stough WG, Abraham WT, Albert NM, Gheorghiade M,
Greenberg BH, et al. Characteristics, treatments, and outcomes of patients
with preserved systolic function hospitalized for heart failure: a report
from the OPTIMIZE-HF registry. J Am Coll Cardiol 2007;50:768e77.
17. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ,
Ponikowski P, Poole-Wilson PA, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task
Force for the diagnosis and treatment of acute and chronic heart failure
2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine
(ESICM). Eur J Heart Fail 2008;10:933e89.
18. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD,
Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of
Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology,
and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010;23:685e713.
19. American College of Cardiology/American Heart Association Task
Force on Practice Guidelines, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Thoracic SurgeonsBonow RO, Carabello BA, Kanu C, de
Leon AC Jr, Faxon DP, Freed MD, et al. ACC/AHA 2006 guidelines
for the management of patients with valvular heart disease: a report of
20.
21.
22.
23.
24.
25.
26.
27.
28.
Aronson et al
671
the American College of Cardiology/American Heart Association
Task Force on Practice Guidelines (writing committee to revise the
1998 Guidelines for the Management of Patients With Valvular Heart
Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.
Circulation 2006;114:e84e231.
Galie N, Palazzini M, Manes A. Pulmonary hypertension and pulmonary arterial hypertension: a clarification is needed. Eur Respir J 2010;
36:986e90.
Mutlak D, Aronson D, Lessick J, Reisner SA, Dabbah S, Agmon Y.
Functional tricuspid regurgitation in patients with pulmonary hypertension: is pulmonary artery pressure the only determinant of regurgitation severity? Chest 2009;135:115e21.
Mullens W, Borowski AG, Curtin R, Grimm RA, Thomas JD,
Tang WH. Mechanical dyssynchrony in advanced decompensated
heart failure: relation to hemodynamic responses to intensive medical
therapy. Heart Rhythm 2008;5:1105e10.
Bursi F, McNallan SM, Redfield MM, Nkomo VT, Lam CS,
Weston SA, et al. Pulmonary pressures and death in heart failure:
a community study. J Am Coll Cardiol 2012;59:222e31.
Mutlak D, Lessick J, Carasso S, Kapeliovich M, Dragu R,
Hammerman H, et al. Utility of pulmonary hypertension for the prediction of heart failure following acute myocardial infarction. Am J
Cardiol 2012;109:1254e9.
Stevenson LW, Zile M, Bennett TD, Kueffer FJ, Jessup ML,
Adamson P, et al. Chronic ambulatory intracardiac pressures and future heart failure events. Circ Heart Fail 2010;3:580e7.
Enriquez-Sarano M, Rossi A, Seward JB, Bailey KR, Tajik AJ. Determinants of pulmonary hypertension in left ventricular dysfunction.
J Am Coll Cardiol 1997;29:153e9.
Voelkel NF, Quaife RA, Leinwand LA, Barst RJ, McGoon MD,
Meldrum DR, et al. Right ventricular function and failure: report of
a National Heart, Lung, and Blood Institute working group on cellular
and molecular mechanisms of right heart failure. Circulation 2006;
114:1883e91.
Thenappan T, Shah SJ, Gomberg-Maitland M, Collander B,
Vallakati A, Shroff P, Rich S. Clinical characteristics of pulmonary hypertension in patients with heart failure and preserved ejection fraction. Circulation. Heart failure 2011;4:257e65.