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This study sought to assess the prognostic value of physical examination in a modern treated heart failure
population.
Background
The physical examination is the cornerstone of the evaluation and monitoring of patients with heart failure. Yet, the
prognostic value of congestive signs (i.e., peripheral edema, jugular venous distension, a third heart sound, and
pulmonary rales) has not been assessed in the current era.
Methods
A post-hoc analysis was conducted on all 1,376 patients, 81% male, mean age 67 11 years, with symptomatic
left ventricular systolic dysfunction enrolled in the AF-CHF (Atrial Fibrillation and Congestive Heart Failure) trial. The
prognostic value of baseline physical examination ndings was assessed in univariate and multivariate Cox
regression analyses.
Results
Peripheral edema was observed in 425 (30.9%), jugular venous distension in 297 (21.6%), a third heart sound in
207 (15.0%), and pulmonary rales in 178 (12.9%) patients. Death from cardiovascular causes occurred in 357
(25.9%) patients over a mean follow-up of 37 19 months. All 4 physical examination ndings were associated
with cardiovascular mortality in univariate analyses (all p values <0.01). In multivariate analyses, taking all 4 signs
as potential covariates, only rales (hazard ratio 1.41; 95% condence interval: 1.07 to 1.86; p 0.013) and
peripheral edema (hazard ratio: 1.25; 95% condence interval: 1.00 to 1.57; p 0.048) were associated with
cardiovascular mortality, independent of other variables.
Conclusions
In the modern era, congestive signs on the physical examination (i.e., peripheral edema, jugular venous distension,
a third heart sound, and pulmonary rales) continue to provide important prognostic information in patients with
congestive heart failure. (J Am Coll Cardiol HF 2014;2:1523) 2014 by the American College of Cardiology
Foundation
16
Caldentey et al.
Physical Examination and Heart Failure
Methods
Study population. A post-hoc analysis was conducted on all
patients enrolled in the AF-CHF (Atrial Fibrillation
and Congestive Heart Failure) trial. The study protocol has
been previously described (15). Briey, the AF-CHF trial was
an international multicenter trial sponsored by the Canadian
Institutes of Health Research that enrolled 1,376 patients
between May 2001 and June 2005 with CHF and nonpermanent atrial brillation. Patients were required to have a
left ventricular ejection fraction (LVEF) 35%, and New
York Heart Association (NYHA) functional class II to IV
symptoms within 6 months of randomization, or functional
class I symptoms if the LVEF was 25% or if the patient was
hospitalized for CHF in the previous 6 months. Patients were
randomized 1:1 to rhythm- or rate-control treatment strategies for atrial brillation. No treatment differences were
observed with respect to the primary outcome (i.e., cardiovascular mortality) and main secondary outcomes (e.g., allcause mortality, heart failurerelated hospitalization, stroke,
quality of life). The study protocol was approved by each
participating centers institutional review board and all patients provided written informed consent.
Pharmacological therapy. The maximum tolerated dose of
beta-blockers (i.e., carvedilol, bisoprolol, or metoprolol) and
angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) was recommended in all
patients. In addition, spironolactone was recommended in
patients on loop diuretics with NYHA functional class III
or IV symptoms. Patients randomized to rhythm-control
received amiodarone as the initial antiarrhythmic drug.
Targeted heart rates for rate-control were <80 beats/min at
rest and <110 beats/min during 6-min walk tests. Anticoagulation was recommended in both treatment arms.
Baseline variables and physical examination. A baseline
physical examination was performed by local site
Baseline Characteristics According to the Presence or Absence of Congestive Signs on the Physical Examination
Peripheral Edema
All Patients
(N 1,376)
Present*
(n 425)
Absent
(n 949)
p Value
Present
(n 297)
Absent
(n 1,072)
Age, yrs
66.7 11.1
68.5 10.0
66.0 11.4
<0.0001
68.3 10.0
66.4 11.3
Male gender
1,118 (81.3)
322 (75.8)
800 (84.3)
0.0002
235 (79.1)
883 (82.4)
25 (1.8)
9 (2.1)
16 (1.7)
0.5800
6 (2.0)
19 (1.7)
718 (52.2)
244 (57.4)
474 (50.0)
0.0105
175 (59.0)
Diabetes mellitus
283 (20.6)
118 (27.8)
164 (17.3)
<0.0001
66 (22.2)
Hypertension
656 (47.7)
233 (54.8)
421 (44.4)
0.0003
149 (50.2)
501 (46.7)
Myocardial infarction
586 (42.6)
193 (45.4)
393 (41.4)
0.1659
141 (47.5)
443 (41.3)
TIA/stroke/bleeding
124 (9.0)
32 (7.5)
92 (9.7)
0.1955
26 (8.7)
98 (9.1)
NYHA functional
class III to IV
431 (31.3)
200 (47.1)
231 (24.3)
<0.0001
158 (53.2)
272 (25.4)
119 19
116 20
120 19
0.0016
117 21
119 19
Heart rate,
beats/min
78 19
80 19
77 19
0.0005
80 20
Left ventricular
ejection fraction, %
26.9 6.0
26.9 5.8
26.8 6.1
0.7011
QRS width, ms
113 30
116 32
113 28
Sodium, mmol/l
139 4
139 4
139 4
Creatinine, mmol/l
112 41
118 42
110 40
0.0002
Atrial brillation
at baseline
788 (57.3)
260 (61.2)
526 (55.5)
0.0488
292 (21.2)
78 (18.3)
214 (22.5)
Diuretics
1,124 (81.7)
375 (88.2)
Beta-blockers
1,085 (78.9)
330 (77.6)
ACE inhibitors
1,185 (86.1)
Aldosterone
antagonists
Absent
(n 1,166)
0.0048
68.3 10.7
66.5 11.1
0.2010
166 (80.2)
955 (81.9)
0.7778
4 (1.9)
21 (1.8)
540 (50.4)
0.0090
122 (58.9)
213 (19.9)
0.3731
37 (17.9)
0.2944
90 (43.5)
0.0579
107 (51.7)
0.8368
<0.0001
Pulmonary Rales
Present
(n 178)
Absent
(n 1,197)
p Value
0.0350
70.1 9.6
66.3 11.2
<0.0001
0.5579
137 (77.0)
986 (83.4)
0.0820
0.8964
3 (1.7)
22 (1.8)
0.8870
596 (51.1)
0.0379
107 (60.1)
611 (51.0)
0.0238
246 (21.1)
0.2907
34 (19.1)
249 (20.8)
0.6005
565 (48.5)
0.1864
99 (55.6)
556 (46.5)
0.0223
479 (41.1)
0.0045
85 (47.7)
501 (41.8)
0.1376
23 (11.1)
101 (8.7)
0.2573
19 (10.7)
105 (8.8)
0.4084
109 (52.7)
321 (27.5)
<0.0001
98 (55.1)
333 (27.8)
0.00455
114 19
120 19
<0.0001
77 19
0.0241
78 18
78 19
0.9000
26.1 6.2
27.1 5.9
0.0196
25.2 6.2
27.1 5.9
0.1182
116 30
113 30
0.2062
117 33
113 29
0.4395
140 4
139 4
0.3990
139 3
139 4
119 40
111 41
<0.0001
119 38
111 42
187 (63.0)
596 (55.6)
0.0242
122 (58.9)
0.0788
50 (16.8)
242 (22.6)
0.0326
747 (78.7)
<0.0001
262 (88.2)
856 (79.8)
753 (79.4)
0.4760
223 (75.1)
856 (79.8)
360 (84.7)
823 (86.7)
0.3179
263 (88.6)
616 (44.8)
219 (51.5)
396 (41.7)
0.0007
Digoxin
886 (64.4)
301 (70.8)
584 (61.5)
Amiodarone
559 (40.6)
166 (39.1)
393 (41.1)
97 (7.1)
20 (4.7)
77 (8.1)
p Value
p Value
Medical history
Black race
Table 1
Clinical characteristics
<0.0001
119 19
0.2532
83 22
77 19
0.0011
26.1 6.2
27.0 6.0
0.0625
0.0873
118 32
113 29
0.0600
0.6704
139 4
139 4
0.5936
0.0004
118 37
112 42
0.0087
663 (56.9)
0.5870
103 (57.9)
684 (57.2)
0.8652
51 (24.6)
241 (20.7)
0.1985
29 (16.3)
263 (22.0)
0.0839
0.0010
184 (88.9)
938 (80.5)
0.0038
158 (88.7)
965 (80.6)
0.0088
0.0752
161 (77.8)
921 (79.0)
0.6946
121 (68.0)
963 (80.5)
0.0001
917 (85.6)
0.1831
179 (86.5)
1004 (86.1)
0.8879
152 (85.4)
1,032 (86.2)
0.7673
157 (52.9)
457 (42.6)
0.0017
104 (50.2)
510 (43.7)
0.0829
89 (50.0)
526 (43.9)
0.1294
0.0009
203 (68.4)
680 (63.4)
0.1171
134 (64.7)
751 (64.4)
0.9280
129 (72.5)
757 (63.2)
0.0164
0.4118
118 (39.7)
439 (40.9)
0.7047
89 (43.0)
470 (40.3)
0.4685
78 (43.8)
481 (40.2)
0.3567
0.0226
21 (7.1)
76 (7.1)
0.9911
18 (8.7)
79 (6.8)
0.3204
9 (5.1)
88 (7.4)
0.2644
<0.0001
Treatment
ICD
Values are mean SD or n (%). *Includes mild (1) or marked (2) peripheral edema.
ACE angiotensin-converting enzyme; AF atrial brillation; ICD implantable cardioverter-debrillator; NYHA New York Heart Association; TIA transient ischemic attack.
Caldentey et al.
Physical Examination and Heart Failure
117 20
17
Caldentey et al.
Physical Examination and Heart Failure
0.0761
<0.0001
<0.0001
0.0004
290 (24.2)
134 (11.2)
94 (7.8)
362 (30.2)
p Valuey
Pulmonary Rales
287 (24.0)
0.1, a user-contributed implementation of sequential generalized regression techniques in SAS (SAS Institute, Cary,
North Carolina).
Two-tailed p values <0.05 were considered statistically
signicant. Statistical testing was performed using SAS
software Version 9.2 (SAS Institute).
<0.0001
Absent
(n 1,197)
18
57 (32.0)
0.0155
Values are n (%). Raw proportions are presented. *Includes mild (1) or marked (2) peripheral edema. yBased on log-rank tests comparing event-free survival.
282 (24.2)
64 (30.9)
0.0008
254 (23.7)
89 (30.0)
0.1442
237 (25.0)
109 (25.6)
Heart failurerelated hospitalization
25 (14.0)
0.1557
130 (11.1)
29 (14.0)
0.1571
119 (11.1)
38 (12.8)
0.0160
58 (13.6)
Sudden cardiac death
101 (10.6)
83 (46.6)
36 (20.2)
0.0149
0.0020
359 (30.8)
102 (8.7)
28 (13.5)
86 (41.5)
<0.0001
<0.0001
43 (14.5)
86 (8.0)
119 (40.1)
<0.0001
67 (7.1)
62 (14.6)
174 (40.9)
All-cause mortality
270 (28.4)
<0.0001
323 (30.1)
70 (39.3)
0.0035
287 (24.6)
70 (33.8)
0.0004
96 (32.3)
139 (32.7)
Cardiovascular mortality
217 (22.9)
<0.0001
258 (24.1)
p Valuey
Absent
(n 1,166)
Present
(n 297)
Present*
(n 425)
Absent
(n 949)
p Valuey
Absent
(n 1,072)
p Valuey
Present
(n 207)
Mortality and Hospitalization Outcomes According to the Presence or Absence of Congestive Signs on the Physical Examination
Table 2
Present
(n 178)
Results
Figure 1
Caldentey et al.
Physical Examination and Heart Failure
19
Kaplan-Meier analysis of event-free survival for the primary endpoint (cardiovascular mortality) according to the presence (red) or absence (blue) of elevated jugular venous
pressure (A), peripheral edema (B), rales (C), and third heart sound (D). Comparisons were performed by log-rank tests.
20
Figure 2
Caldentey et al.
Physical Examination and Heart Failure
Kaplan-Meier Estimates of Secondary Outcomes, in Patients With at Least 1 Positive Congestive Sign on
Physical Examination Versus None
Freedom from cardiovascular mortality (A), all-cause mortality (B), heart failurerelated death (C), and heart failurerelated hospitalization (D) are plotted in patients with at
least 1 positive congestive sign on the physical examination (red) versus none (blue). Comparisons were performed by log-rank tests.
examination continue to provide relevant prognostic information. Peripheral edema, jugular venous distension, a third
heart sound, and pulmonary edema were each associated
with increased cardiovascular mortality, all-cause mortality,
and heart failurerelated death. In addition, peripheral
edema was signicantly associated with sudden cardiac
death, and jugular venous distension, a third heart sound,
and pulmonary edema with heart failurerelated hospitalizations. In multivariate analyses that included standard
clinical, electrocardiographic, and echocardiographic parameters: 1) peripheral edema and pulmonary rales remained
independent predictors of all-cause and cardiovascular
mortality, associated with a 2-fold increased risk of heart
failurerelated death; 2) pulmonary rales independently
predicted hospitalizations for heart failure; and 3) jugular
venous distension was associated with a 48% increased risk
of heart failurerelated death.
The few studies that addressed the prognostic value of
congestive signs in the setting of acute heart failure have
yielded consistent results (16,17). The presence of an S3
has been associated with mortality in patients listed for
0.721.16
0.91
The primary analysis was adjusted for the following baseline variables: age, sex, left ventricular ejection fraction, New York Heart Association functional class, the presence or absence of diabetes or hypertension, the use or nonuse of an internal debrillator, the time since the
diagnosis of atrial brillation, the creatinine level, and the use or nonuse of a beta-blocker, angiotensin-converting enzyme inhibitor, or oral anticoagulant. Signicant p values are in bold.
CI condence interval.
0.3307
0.0211
1.051.90
1.42
0.0003
0.991.90
1.37
0.4557
1.22
0.951.58
0.1208
1.11
0.841.48
0.4735
0.801.92
1.24
0.6871
0.721.64
1.09
0.3517
0.831.71
1.19
0.0286
1.402.85
1.99
0.0584
1.423.17
2.12
0.9902
0.641.54
1.00
0.0458
1.012.17
1.48
0.0097
0.0001
1.031.69
1.091.88
1.43
1.32
0.4695
0.4489
0.851.46
0.861.39
1.09
1.11
0.1406
0.1387
0.951.47
0.941.54
1.20
1.18
0.0055
1.091.61
1.32
All-cause mortality
0.0130
1.061.65
1.32
Cardiovascular mortality
0.941.48
1.18
Multivariate analyses
0.0773
0.0004
1.252.21
1.67
0.0160
1.061.84
1.40
1.181.93
<0.0001
1.082.05
1.49
0.1432
1.51
0.0010
0.962.25
1.47
0.1580
0.892.00
1.34
0.1415
0.911.89
1.31
<0.0001
0.0165
2.054.43
3.02
0.0165
1.102.54
1.67
0.0002
2.03
1.683.35
2.37
<0.0001
1.412.92
1.432.31
1.482.50
1.92
1.82
0.0023
0.0040
1.131.91
1.141.83
1.44
1.47
1.51
1.372.01
1.66
1.52
1.332.03
1.64
All-cause mortality
<0.0001
Caldentey et al.
Physical Examination and Heart Failure
Cardiovascular mortality
<0.0001
1.211.93
0.0004
p Value
95% CI
Hazard ratio
p Value
95% CI
Hazard ratio
Univariate analyses
0.0001
p Value
95% CI
Hazard ratio
Univariate and Multivariate Hazard Ratios for the Congestive Signs on Physical Examination
Table 3
1.221.86
95% CI
Hazard ratio
Pulmonary Rales
p Value
<0.0001
21
over 25 years ago in whom less than 10% received betablockers, ACE inhibitors were randomly allocated, and 9%
were treated with potassium sparing diuretics. In contrast, a
substudy from the Digitalis Investigator Group created a
global congestion score that combined the 4 physical examination signs assessed in our study along with symptoms
and radiological ndings (23). This score independently
predicted mortality at 36 months in patients with systolic
dysfunction on ACE inhibitors. Because the individual
contribution of physical signs was not independently
analyzed, the prognostic value of each cannot be surmised.
Moreover, concomitant use of beta-blockers and aldosterone
antagonists was not reported.
A community-based study reported that a combination
of right- and left-sided congestive signs predicted cardiovascular mortality in patients with CHF and preserved or
depressed left ventricular function (24). Analyses were
not specically conducted in the subgroup of patients
(45%) with left ventricular systolic dysfunction. Compared
to our study population, patients had less advanced heart
failure, as reected by a higher LVEF (34 6%) and
lower prevalence of congestive signs (e.g., rales 4%). Only
38% received an ACE inhibitor or ARB and 45% a betablocker. More recently, a retrospective analysis of 2,647
patients with NYHA functional class III to IV symptoms
enrolled in the CIBIS-II (Cardiac Insufciency Bisoprolol
Study-II) trial found that jugular venous distension
and ascites were independently associated with renal
dysfunction and all-cause mortality (25). Peripheral edema
and jugular venous distension were also associated with
heart failure deaths and cardiovascular hospitalizations.
Importantly, the prognostic value of pulmonary rales was
not assessed. As in other studies, beta-blockers and aldosterone antagonists were underprescribed according to
current standards (50% and 10% of the population, respectively) (25).
In our more contemporary patient population, 86%
received ACE inhibitors, 79% beta-blockers, and 45%
aldosterone antagonists. All 4 congestive signs (i.e., peripheral edema, jugular venous distension, the presence of a
third heart sound, and pulmonary rales) were associated with
increased cardiovascular mortality. Interestingly, physical
examination ndings associated with edema (i.e., peripheral
edema and pulmonary rales) remained more powerful independent predictors of cardiovascular outcomes than jugular
venous distension and a third heart sound. Increased
hydrostatic pressure in right heart cavities is transmitted to
systemic veins and capillaries, leading to venous congestion
(including jugular distension), peripheral edema, and/or
ascites. While increased central venous pressures by catheterization have been associated with worsening renal function and prognosis in patients with CHF (2628), jugular
venous distension on physical examination frequently underestimates right atrial pressures (29). In contrast, peripheral edema may be considered a more advanced marker of
heart failure in that it represents the inability of the
22
Caldentey et al.
Physical Examination and Heart Failure
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Caldentey et al.
Physical Examination and Heart Failure
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23
heart failure
outcomes
physical