JACC: HEART FAILURE VOL. 6, NO.

4, 2018

ª 2018 PUBLISHED BY ELSEVIER ON BEHALF OF THE

AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

MINI-FOCUS ISSUE: HOSPTIALIZED HEART FAILURE AND CONGESTION

STATE-OF-THE-ART REVIEW

Integrative Assessment of Congestion

in Heart Failure Throughout the
Patient Journey
Nicolas Girerd, MD, PHD,a Marie-France Seronde, MD, PHD,b Stefano Coiro, MD,c Tahar Chouihed, MD,a,d
Pascal Bilbault, MD, PHD,e François Braun, MD,f David Kenizou, MD,g Bruno Maillier, MD,h
Pierre Nazeyrollas, MD, PHD,i Gérard Roul, MD, PHD,j Ludivine Fillieux, PHARMD,k William T. Abraham, MD,l
James Januzzi, JR, MD,m Laurent Sebbag, MD, PHD,n Faiez Zannad, MD, PHD,a Alexandre Mebazaa, MD, PHD,o
Patrick Rossignol, MD, PHD,a on behalf of INI-CRCT, Great Network, and the EF-HF Group

ABSTRACT

Congestion is one of the main predictors of poor patient outcome in patients with heart failure. However, congestion
is difficult to assess, especially when symptoms are mild. Although numerous clinical scores, imaging tools, and
biological tests are available to assist physicians in ascertaining and quantifying congestion, not all are appropriate for
use in all stages of patient management. In recent years, multidisciplinary management in the community has become
increasingly important to prevent heart failure hospitalizations. Electronic alert systems and communication
platforms are emerging that could be used to facilitate patient home monitoring that identifies congestion from heart
failure decompensation at an earlier stage. This paper describes the role of congestion detection methods at key
stages of patient care: pre-admission, admission to the emergency department, in-hospital management, and lastly,
discharge and continued monitoring in the community. The multidisciplinary working group, which consisted of
cardiologists, emergency physicians, and a nephrologist with both clinical and research backgrounds, reviewed the
current literature regarding the various scores, tools, and tests to detect and quantify congestion. This paper
describes the role of each tool at key stages of patient care and discusses the advantages of telemedicine as a means
of providing true integrated patient care. (J Am Coll Cardiol HF 2018;6:273–85) © 2018 Published by Elsevier on
behalf of the American College of Cardiology Foundation.

From the aINSERM, Centre d’Investigations Cliniques 1433, Université de Lorraine, CHU de Nancy, Institut Lorrain du Coeur et des
Vaisseaux, Nancy, France, Inserm 1116 and INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN Network, Nancy, France;
b
Service de cardiologie CHU de Besançon, EA 3920, Unité INSERM 942 CHU Lariboisière, Paris, France; cDivision of Cardiology,
University of Perugia, School of Medicine, Perugia, Italy; dEmergency Department, CHU de Nancy, France; eEmergency Depart-
ment, Hôpitaux Universitaires de Strasbourg, Strasbourg, France and EA 7293 Stress vasculaire, Fédération de Médecine Trans-
lationnelle de Strasbourg, Strasbourg, France; fStructures de Médecine d’Urgence, Centre Hospitalier Régional, Hôpital de Mercy,
Metz, France; gService de cardiologie, Hôpital Emile Muller, Mulhouse, France; hService de cardiologie, Centre hospitalier de
Troyes, Anatole, France; iCentre de Recherche et d’Investigation Clinique, Service de Cardiologie, CHU de Reims, Reims, France;
j
Pôle d’activité médico-chirurgicale cardiovasculaire Nouvel Hôpital Civil, Strasbourg, France and Unité d’insuffisance cardiaque,
Centre de compétence des cardiomyopathies; kNovartis Pharma SAS, Rueil-Malmaison, France; lDavis Heart and Lung Research
m
Institute, Ohio State University, Columbus, Ohio; Division of Cardiology, Massachusetts General Hospital, Boston, Massachu-
setts; nHospices Civils de Lyon, Hôpital Louis Pradel, Pôle Médico-Chirurgical de Transplantation Cardiaque Adulte, Bron, France;
and the oDepartment of Anesthesiology, Critical Care and Burn Unit, St. Louis Hospital, University Paris, UMR-S942, INSERM and
INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN Network Nancy, GREAT Network, Paris, France. Drs. Girerd,
Seronde, Coiro, Chouihed, Bilbaut, Braun, Kenizou, Mailleri, Nazeyrollas, and Rossignol received board fees from Novartis. Drs.
Rossignol, Zannad, Mebazaa, Chouihed, and Girerd are supported by a public grant overseen by the French National Research
Agency (ANR) as part of the second “Investissements d’Avenir” programme (ANR-15-RHU-0004). Dr. Fillieux is an employee of
Novartis. Dr. Abraham is the co-principal investigator (PI) of the CHAMPION trial; a member of Steering Committees of the
REDUCEhf and COMPASS-HF trials; is a PI of HOMEOSTASIS trial; and has received consulting fees from St. Jude Medical
and Medtronic. Dr. Januzzi has received grant support from Siemens, Singulex, and Prevencio; consulting income from Roche

ISSN 2213-1779/$36.00 https://doi.org/10.1016/j.jchf.2017.09.023

274 Girerd et al. JACC: HEART FAILURE VOL. 6, NO. 4, 2018

Assessing Congestion in Patients With HF APRIL 2018:273–85

P
ACRONYMS AND atients with heart failure (HF) often The objective of this position paper is to outline the
ABBREVIATIONS develop congestion that may require 4 types of tools for evaluating and quantifying
urgent hospitalization, especially if congestion, namely: 1) clinical tools and scores; 2)
AHF = acute heart failure
pulmonary congestion (PC) is present. Devel- biological biomarkers; 3) imaging; and 4) pressure
BNP = B-type natriuretic
opment of congestion leading to HF decom- (hemodynamics) and impedance-based tools. The
peptide
pensation is a powerful predictor of poor role of each tool is described during key stages of
EF = ejection fraction
patient outcome (1–5). Therefore, it may be patient care and according to the main points of
HF = heart failure
important to better detect and monitor clinical care.
LUS = lung ultrasound
congestion before it leads to decompensa-
LV = left ventricular
tion. However, congestion can be difficult
CLINICAL TOOLS FOR
NP = natriuretic peptide to assess, especially when extrapulmonary
EVALUATING CONGESTION
NT-proBNP = N-terminal signs of congestion are mild, such as in the
fragment pro- B-type SIGNS AND SYMPTOMS OF CONGESTION. Physical
setting of acute PC due to hypertension or
natriuretic peptide
assessment can only detect a moderate to high level
in patients nearing discharge from a HF
PC = pulmonary congestion of congestion. Although many clinical signs and
hospitalization.
symptoms of congestion have been well characterized
Increased intracardiac filling pressures often
and are recognized by published guidelines (8), no
silently precede the appearance of congestive symp-
single element from clinical history or physical ex-
toms by days or weeks (1). Increasing filling pressures
amination can accurately detect the underlying he-
are often subtle and difficult to detect, and can be
modynamic changes that lead to congestion.
masked by other comorbidities (e.g., infections).
Dyspnea, orthopnea, systemic edema, jugular venous
Current European Society of Cardiology guidelines
pressure, and the third heart sound are all important
recommend treating signs and symptoms of conges-
clinical findings to identify decompensated HF. A
tion so that patients achieve near-optimal volume
review of clinical signs and symptoms is detailed in
status (6,7). Unfortunately, 50% of patients admitted
the Online Appendix. However, relying on only 1
for acute heart failure (AHF) are discharged with re-
single clinical finding to identify decompensated HF
sidual congestion (2), possibly due to an absence of a
has a low sensitivity and poor predictive value (9),
clear congestion evaluation strategy. Such residual
whereas the reproducibility of the medical interview,
congestion at discharge is associated with rehospi-
especially to assess dyspnea, is poor (10).
talization and death within 6 months after discharge,
independent of the underlying pathology (2). Impor- CLINICAL CONGESTION SCORES. Clinical scores that
tantly, although current guidelines emphasize the combine several clinical indicators have been shown to
importance of aggressively treating congestion, they assess the level of congestion more accurately than any
do not stipulate which congestion targets should be standalone indicator (9). Yet, they are more often used
aimed at discharge for AHF hospitalization or in an as prognostic rather than diagnostic tools. The Ste-
ambulatory setting. venson classification, Lucas Score, and Rhode Score
At each stage of the journey of a patient with HF, are detailed in the Online Appendix and are reported in
specific evaluation tools are used to qualify and Table 1. The EVEREST score, which was developed by
quantify congestion to support treatment decisions. Ambrosy et al. in 2013 (2) within the EVEREST (Efficacy
However, not all of these tools are appropriate for use of Vasopressin Antagonism in Heart Failure Outcome
at each point of clinical care within this journey (i.e., Study with Tolvaptan) trial (Table 1), captures changes
clinical settings where a patient may be managed). in congestion within a hospitalization time frame and

Diagnostics, Critical Diagnostics, Sphingotec, Phillips, and Novartis; and participates in clinical endpoint committees/data safety
monitoring boards for Novartis, Amgen, Janssen, and Boehringer Ingelheim. Dr. Zannad is a compensated board member for
Boston Scientific; a consultant for Boston Scientific, CVRx, LivaNova, Janssen, Bayer, Pfizer, Novartis, Resmed, Amgen,
Quantum Genomics, Takeda, General Electric, Boehringer, Relypsa, ZS Pharma, AstraZeneca, and Roche Diagnostics; and is
a compensated speaker with Pfizer and AstraZeneca. Dr. Mebaza has received speaker honoraria from The Medicines
Company, Novartis, Orion, Roche, Servier, and Vifor Pharma; and has received fees as member of advisory board and/or
steering committee from Cardiorentis, The Medicine Company, Adrenomed, MyCartis, and Critical Diagnostics. Dr. Rossi-
gnol is a consultant for Bayer, Relypsa, AstraZeneca, Stealth Peptides, Fresenius, Vifor Fresenius Medical Care Renal
Pharma, and CTMA; has received lecture fees from CVRx from Relypsa; and is the cofounder of CardioRenal Diagnostics. All
other authors have reported that they have no relationships relevant to the contents of this paper to disclose. John R.
Teerlink, MD, served as Guest Editor for this paper.

Manuscript received January 30, 2017; revised manuscript received September 15, 2017, accepted September 26, 2017.
JACC: HEART FAILURE VOL. 6, NO. 4, 2018 Girerd et al. 275
APRIL 2018:273–85 Assessing Congestion in Patients With HF

T A B L E 1 Summary of Key Scores

Key Clinical and Mixed Clinical/Biomarker Scores

Lucas Score Rohde Score EVEREST Score Gheorgiade Score

(Online Ref. 11) (Online Ref. 12) (Online Ref. 7) (4)

Dyspnea 0 ¼ None
1 ¼ Seldom
2 ¼ Frequent
3 ¼ Continuous
Orthopnea 1 ¼ Any respiratory distress Evaluated during the 0 ¼ None 0 ¼ None
associated with lying last week 1 ¼ Seldom 1 ¼ Mild (1 pillow)
down or perceived need to Graded from 0 to 4 2 ¼ Frequent 2 ¼ Moderate (>1 pillow)
use >1 pillow to avoid 0 ¼ Need no more than 3 ¼ Continuous 3 ¼ Severe (sleeps sitting)
respiratory distress 1 pillow
4 ¼ At least 1 night spent
sleeping in a sitting
position
JVD* 1 ¼ $10 cm H2O Graded from 0 to 4 0 ¼ #6 1 ¼ <8 and no hepatojugular reflux
0 ¼ Jugulars not visible 1 ¼ 6–9 1 ¼ 8–10 or hepatojugular reflux
4 ¼ Crests visible at the 2 ¼ 10–15 2 ¼ 11–15
earlobe with the 3 ¼ $15 3 ¼ >16
patient at 30 to 45
Rales 0 ¼ None 0 ¼ None
1 ¼ <25% 1 ¼ Bases
2 ¼ 25%50% 2 ¼ Up to <50%
3 ¼ >50% 3 ¼ >50%
4 ¼ Entire lung
Edema 1 ¼ Yes 0 ¼ None 0 ¼ Absent/trace 0 ¼ None
1–4 ¼ According to the 1 ¼ Slight 1 ¼ 1þ
indentation at the 2 ¼ Moderate 2 ¼ 2þ
ankle 3 ¼ Marked 3 ¼ 3þ/4þ
Other bedside 1 ¼ Increase diuretics during 1 ¼ Third heart sound Fatigue: Hepatomegaly:
parameters the past week 0 ¼ None 1 ¼ Absent in the setting of normal JVP
1 ¼ $2 lbs increase since the 1 ¼ Seldom 0 ¼ Absent
previous clinic visit 2 ¼ Frequent 1 ¼ Liver edge
3 ¼ Continuous 2 ¼ Moderate pulsatile enlargement
3 ¼ Massive tender enlargement
extending to midline
Dynamic Orthostatic testing:
parameters 1 ¼ Significant SBP decrease
or HR increase
0 ¼ No change in SBP or
HR and no difficulty
1 ¼ Mild difficulty/2 ¼ Moderate
3 ¼ Severe/worst
6-min walk test:
1 ¼ >400 m/0 ¼ 300–400 m
1 ¼ 200–300 m/2 ¼ 100–200 m
3 ¼ <100 m
Valsalva maneuver:
1 ¼ Normal response
1 ¼ Absent overshoot pattern
2 ¼ Square wave pattern
Nonclinical BNP (pg/ml):
parameters 0 ¼ <100/1 ¼ 100–299
2 ¼ 300–500/3 ¼ >500
NT-proBNP (pg/ml):
0 ¼ <400/1 ¼ 400–1,500
2 ¼ 1,500–3,000/3 ¼ >3,000
Setting 4–6 weeks after discharge HF outpatient clinic Discharge from HF hospitalization
from HF hospitalization
Interpretation 0 ¼ no congestion $5 ¼ Increased right and A score from 0–18 can be No cutoffs are specified.
1–2 ¼ mild congestion left atrial pressure obtained. This score emerged from an expert
3–5 ¼ major congestion compared with Having a discharge score $1 consensus. It was not constructed
The score predicts 2-yr patients with no HF is associated with a 10% from a clinical cohort.
survival: signs (score ¼ 0) absolute increase in the
0 ¼ 13% mortality $3 ¼ Increased the probability of
1–2 ¼ 33% mortality absolute 6-month hospitalization at 6 months.
3–5 ¼ 59% mortality mortality risk by 25%. Having a discharge score $3 is
associated with a 10%
absolute increase in the
probability of all-cause death
at 6 months.

*Jugular vein distention (JVD) is measured in seated patients.

BNP ¼ B-type natriuretic peptide; HF ¼ heart failure; HR ¼ heart rate; JVP ¼ jugular vein pressure; NT-proBNP ¼ N-terminal factor pro-B-type natriuretic peptide; SBP ¼ systolic blood pressure.
276 Girerd et al. JACC: HEART FAILURE VOL. 6, NO. 4, 2018

Assessing Congestion in Patients With HF APRIL 2018:273–85

is associated with a markedly increased risk of HF can alternately be a marker of congestion or it may
mortality in the 15% of patients with overt clinical imply adequate decongestion; increased venous
congestion (2). The Gheorghiade score (4) has been congestion has been elegantly shown to be the
promoted as an integrative congestion score, inte- most important hemodynamic factor driving wors-
grating bedside clinical parameters, dynamic parame- ening renal function in decompensated patients (5).
ters, and natriuretic peptides (NPs) (Table 1). However, other causes of renal dysfunction (dehy-
The respective role of these congestion scores in dration following an intensive decongestion, neph-
routine clinical practice still remains to be determined. roangiosclerosis, and drug adverse effects) are
However, the EVEREST score is the most evidence- frequently observed in patients with HF. The blood
based in the current era of AHF management, and it urea nitrogen to creatinine ratio is a useful variable to
appears to be the best candidate for routine use. better identify patients with renal dysfunction due to
congestion (15).
CIRCULATING BIOMARKERS FOR
LIVER FUNCTION MARKERS. Cholestatic liver injury
EVALUATING CONGESTION
due to congestion is primarily observed when central
venous pressure is particularly high. The resulting
NPs, such as B-type natriuretic peptide (BNP),
right atrial pressure transmitted directly to the he-
N-terminal fragment pro-B-type natriuretic peptide
patic veins impairs hepatocyte function (16). There-
(NT-proBNP), and atrial NP, are the most studied
fore, bilirubin and gamma-glutamyl transpeptidase
circulating biomarkers in HF. The characteristics of
have been suggested as possible biomarkers for
NPs are listed in Online Table 1.
congestion in the appropriate clinical setting.
Current clinical practice guidelines recommend BNP
or NT-proBNP for assisting with the diagnosis of AHF IMAGING TOOLS FOR
(7,11). Biomarkers are also useful for determining EVALUATING CONGESTION
prognosis after hospitalization, as well as in the chronic
phase of HF. NT-proBNP is likely to become the stan- Radiological findings reflect the anatomical and
dard because of its better risk-stratifying properties in pathological alterations induced by PC. Traditionally,
the setting of AHF (12) and its straightforward inter- a chest x-ray is the first-line procedure. X-ray signs
pretation in patients treated with sacubitril/valsartan. (including peri-bronchial cuffing, cardiomegaly, pul-
PLASMA VOLUME, HEMOCONCENTRATION. Several monary venous congestion, or pleural effusion) are
routinely assessed biological parameters, such as reasonably specific but poorly sensitive; negative
serum protein, albumin, hemoglobin, and hematocrit chest x-ray findings have been reported in a sub-
have been proposed as surrogate markers of (de) stantial percentage of patients with AHF (17).
congestion and have been found to be associated with Echocardiography is currently the gold standard
cardiovascular endpoints (13). non invasive tool for detecting and monitoring HF. It
Several formulas have also been developed to is most useful in the assessment of HF etiology and in
indirectly estimate plasma volume, using hemoglobin classifying HF according to the left ventricular (LV)
and/or hematocrit, which may therefore be valuable ejection fraction (EF).
for monitoring both acute and chronic (de)congestion Comprehensive echocardiography may serve as a
(14). One simple formula to assess estimated plasma baseline for serial evaluations in patients whose
volume variations is the Strauss formula: clinical status may change over time as disease pro-
gresses or it may be used to follow therapeutic in-
% change in plasma volume ¼ 100 terventions (18). However, it involves a lengthy
hemoglobinðbeforeÞ 1  hematocritðafterÞ procedure that is typically not performed at bedside
   100
hemoglobinðafterÞ 1  hematocritðbeforeÞ
other than in intensive care units. Logistically, it is
impractical to repeatedly perform these examina-
An instantaneous version of this formula (Duarte’s
tions; thus, comprehensive echocardiography is not
formula [14]) enables calculating plasma volume
usually performed at discharge if already performed
without previous hemoglobin and hematocrit data:
during hospitalization. Furthermore, the algorithm
1  hematocrit used to determine elevated filling pressures can only
ePVS ¼  100
hemoglobinðg=dlÞ be performed by an experienced cardiologist skilled
in echocardiography. Despite these drawbacks,
RENAL MARKERS. Evaluating renal function is part echocardiography remains the gold standard for
of routine care in AHF and has links with evaluating evaluating blood volume and LV filling pressures
and managing congestion. Worsening renal function before discharge (18). It is superior to clinical scores
JACC: HEART FAILURE VOL. 6, NO. 4, 2018 Girerd et al. 277
APRIL 2018:273–85 Assessing Congestion in Patients With HF

F I G U R E 1 Quantification of Pulmonary Congestion and Systemic Congestion Using Echocardiography

Lung ultrasound and quantification of inferior vena cava (IVC) diameters through respiratory cycles. (A and B) Two techniques for quantifying pulmonary congestion
using lung ultrasound (LUS). With the 28 scanning-site LUS technique, a precise quantification of extravascular lung water can be achieved; 16 to 30 comets
(also called B-lines) detected in the entire lung are evocative of moderate pulmonary congestion and >30 comets are evocative of severe pulmonary congestion.
The 8-region LUS technique is a semiquantitative technique. A positive region is defined by the presence of $3 B-lines in a longitudinal plane between 2 ribs and $2
positive regions on each lung, which suggest significant pulmonary congestion. LUS lasts <5 min using both techniques. (C) Upper images: Normally aerated lung and
regular interstitium, the only image that can be visualized below the pleural line is the reflection of the chest wall from the probe to the parietal pleura (A lines), or a
few vertical artifacts can be detected (images with 1 and 2 lung comets). (C) Bottom images: Progressive extravascular lung water accumulation as shown by the
increasing number of lung comets. Lung comets are a simple echographic sign, originating from water thickened interlobular septa. Frequently, images evaluation is
much less reproducible and reliable than video loops, which are important to determine the number of lung comets when they are numerous. Evaluating still images
may be complicated by variations in comet position and strength, as well as a variety of image artifacts that typically occur with lung imaging. These mostly stem from
secondary reflections from the lung surface, and are not comets, resulting in a widely varying comet count. In addition, when comet tail artifacts are confluent, only
real-time loops permit an efficient counting. Even if real-time analysis is more difficult for inexperienced practitioners, we strongly advise using loops to quantify lung
comet count, especially in patients with a moderate to high degree of pulmonary congestion. (Right panels) Right atrial pressures can be assessed with IVC diameters
as shown in the upper and lower right panels.

alone for predicting readmission over short- to cava diameter, ejection fraction, and the right atrial
medium-term follow-up (19). volume index.
In the emergency department or during clinical Lung ultrasound (LUS) is highly useful in
points of care, simple echocardiography may be per- comprehensive congestion evaluation at the bedside.
formed relatively easily with portable, pocket-sized LUS produces comet-like images, and the number of
ultrasound devices. These devices are capable of “comets” viewed is proportional to the severity of
measuring important variables such as inferior vena congestion (Figure 1). LUS effectively measures the
278 Girerd et al. JACC: HEART FAILURE VOL. 6, NO. 4, 2018

Assessing Congestion in Patients With HF APRIL 2018:273–85

amount of intrapulmonary fluid, indicating PC, appropriate discharge (Central Illustration, Online
which is associated with the level of pulmonary Table 2).
arterial pressure (20). LUS provides useful informa- PRE-HOSPITAL AND EMERGENCY DEPARTMENT.
tion for the prognostic stratification of patients Before hospital arrival, the objective is to accurately
admitted to the emergency department with dyspnea identify AHF and direct the patient to the appropriate
and/or chest pain syndrome (21). In patients hospi- service. The tools are mainly related to clinical
talized for AHF, residual PC as assessed by LUS is a assessment (including patient history, clinical evalu-
strong predictor of post-discharge outcome (3). ation of breathlessness, and physical examination to
Minimum training is required; reproducible results assess signs of HF) and may include LUS, BNP, or NT-
have been obtained after 30 min to 1 h of training proBNP measurement. Preliminary data regarding the
(22). This technique can rapidly detect changes in use of pre-hospital LUS are promising (26). In the
congestion over a few hours using freely emergency department, most validated tools for
available and easy to use hand-held ultrasound assessing congestion are routinely available. In
devices (23). particular, our group recommends that LUS should be
PRESSURE AND IMPEDANCE-BASED TOOLS systematically performed, because it is easy to use,
and results are rapid. We also recommend confirming
In some difficult clinical settings, right heart cathe- the diagnosis with either BNP or NT-proBNP dosing as
terization (details described in the Online Appendix) recommended by the current clinical guidelines,
remains the gold standard assessment to evaluate although the results can take several hours to pro-
both right ventricular and LV filling pressures and duce. Because patients with AHF benefit from early
hemodynamic congestion. initiation of therapeutic interventions (27), conges-
Importantly, and in contrast to the ESCAPE (Eval- tion should be treated as early as possible based on
uation study of congestive heart failure and pulmo- the LUS results. Therapy can be adjusted later
nary artery catheterization effectiveness) results, the according to the BNP or NT-proBNP results. A chest
CHAMPION (CardioMEMS Heart Sensor Allows Moni- x-ray should also be systematically performed in the
toring of Pressure to Improve Outcomes in NYHA emergency department.
Class III Heart Failure Patients) trial demonstrated
HOSPITALIZATION COURSE THROUGH DISCHARGE. The
that tailoring HF management to achieve protocol-
objective of care in the hospitalized setting is to
defined pulmonary artery pressures according to a
monitor changes in congestion level and overall
long-term implanted wireless pulmonary artery he-
condition following treatment in patients admitted
modynamic monitoring system was associated with
for congestive symptoms. Because of the risk of
fewer HF hospitalizations in patients with chronic HF
rehospitalization observed in these patients, which is
(1). In CHAMPION, a significant reduction in HF hos-
attributable to residual congestion at discharge, we
pitalizations was observed in patients with HF
recommend using a repeated multiparameter testing
reduced EF and patients with HF preserved EF,
strategy to achieve the best possible decongestion.
making pressure-guided HF therapy an option for HF
This would involve clinical examinations (EVEREST
patients, regardless of LVEF (24). The use of these
score), quantitative dyspnea evaluation (Likert,
wireless devices may change the management of AHF
visual analogic score), biological biomarkers (BNP/
and chronic HF, especially the management of
NT-proBNP concentrations, plasma volume estima-
congestion in the near future.
tion based on hematologic data, and liver and kidney
Bioimpedance vector analysis is a promising
biomarkers in appropriate patients), and ultrasounds
noninvasive technique (Online Appendix). Of note,
(both echocardiography and LUS).
the IMPEDANCE-HF (Outpatient Lung Impedance-
Although clinical evaluation is typically per-
Guided Preventive Therapy in Patients With Chronic
formed repeatedly within routine care, only refined
Heart Failure) trial recently demonstrated that lung
clinical scoring such as the EVEREST score can
bioimpedance-guided management could reduce
identify rapid congestion changes, except in patients
hospitalization rates (25).
in whom the baseline congestion level is mild.
APPLYING THE RIGHT TOOL FOR EACH However, this clinical score is time-consuming and
STAGE OF PATIENT MANAGEMENT requires clinical expertise; it is rarely performed
with routine care.
Based on the preceding literature review, the authors NPs could be used to guide decongestion therapy.
recommend the following parameters for evaluating However, the half-life of NT-proBNP renders it un-
congestion at each step of patient management until suitable to assess rapid congestion changes, and the
JACC: HEART FAILURE VOL. 6, NO. 4, 2018 Girerd et al. 279
APRIL 2018:273–85 Assessing Congestion in Patients With HF

C ENTR AL I LL U STRA T I O N Congestion Assessment in HF Patient Journey

Girerd, N. et al. J Am Coll Cardiol HF. 2018;6(4):273–85.

BNP ¼ B-type natriuretic peptide; HF ¼ heart failure; IVC ¼ inferior vena cava; NP ¼ natriuretic peptide.
280 Girerd et al. JACC: HEART FAILURE VOL. 6, NO. 4, 2018

Assessing Congestion in Patients With HF APRIL 2018:273–85

T A B L E 2 Selected Set of Decongestion Targets at Discharge From Hospitalization for Worsening Heart Failure

Congestion Parameter Target at Discharge Reference

Clinical tools
EVEREST score #2 Ambrosy et al. (2).
NYHA functional class #2 Salah et al. The ELAN-HF study. Heart 2014;100:115–25
Biomarkers
NT-proBNP >30% drop during hospitalization McQuade et al. (28).
Discharge value <1,500 pg/ml Salah et al. The ELAN-HF study. Heart 2014;100:115–25
and Kociol et al. The DOSE-AHF trial. Circ Heart Fail 2013;6:240–5
BNP Discharge value <250 pg/ml McQuade et al. (28)
Hemoglobin >10 g/l increase during hospitalization Van der Meer et al. The PROTECT trial. J Am Coll Cardiol 2013;61:1973–81
Imaging tools
IVC imaging Maximum diameter <2.1 cm Goonewardena et al. J Am Coll Cardiol Img 2008;1:595–601
IVC collapsibility index >50%
Lung ultrasound <30 us-B lines Coiro et al. (3) and Gargani. Cardiovasc Ultrasound 2015;13:40

IVC ¼ inferior vena cava; NYHA ¼ New York Heart Association; us ¼ ultrasound.

cost of both BNP and NT-proBNP measurements Typically, multimodal congestion assessment
makes daily quantification uneconomical and not could be most useful upon admission, during decon-
recommended. However, a lack of reduction of at gestion therapy, and upon discharge. Ideally, optimal
least 30% in the pre-discharge value for either pep- decongestion should be achieved before patients are
tide or a discharge BNP <250 pg/ml reveals the lack of discharged, especially in wet and warm patients with
significant decongestion and of a high risk for repeat overt signs of clinical congestion at admission, and in
hospitalization and/or death (28). The Strauss for- whom congestion is the key driver of hospitalization.
mula, based on hemoglobin and hematocrit levels, is A selected set of decongestion targets to achieve
a useful, inexpensive, and simple method to assess before discharge are proposed in Table 2.
daily hemoconcentrations. Nonetheless, it is scarcely POST-DISCHARGE AND LONG-TERM MANAGEMENT.
used despite these practical advantages (29). Patients with AHF remain at high risk of death and
Echocardiography can be repeatedly performed rehospitalization in the months after discharge; as
during a hospitalization for AHF. However, additional many as 35% of patients are readmitted for AHF
echographic examinations would be impractical to within a month after the index AHF hospitalization
perform. In contrast, LUS and inferior vena cava echo discharge (31). With each rehospitalization, the risk of
can be performed at the bedside with a hand-held mortality rises. Accordingly, once discharged, a
device in several minutes. This simple heart and multidisciplinary disease management team focused
lung ultrasound captures rapid changes in congestion on HF, which includes a cardiologist, a general
and provides valuable information to guide choices practitioner, and a HF nurse, should follow the pa-
for decongestion therapy (23,30), and may represent tient to reduce the risk of rehospitalization (7).
the extension of clinical examination in patients with Because of the frequency of early rehospitalizations,
AHF. the first post-discharge visit with general practi-
Other multimodal evaluations could be envisioned, tioners is advisable within 7 days after the initial
including clinical evaluations, with special focus on discharge and with the hospital cardiology team
the determination of dry weight and BNP and/or within 2 weeks (7). During this phase, simplified
NT-proBNP quantification at discharge. Measuring clinical, biological and imaging resources should be
in-hospital changes in estimated plasma volume and used. Patient-reported clinical status and BNP and/or
comprehensive but simple cardiac and lung echo- NT-proBNP or plasma volume, because of their scal-
graphic data could become the tools of choice during able nature, would be particularly useful in this
hospitalization and could be included in this multi- setting (Central Illustration, Online Table 2). In
modal evaluation at discharge. LUS- and simplified agreement with others (32), we also strongly recom-
echocardiographybased in-hospital management of mend going beyond the clinical evaluation because
AHF patients has been recently shown to decrease the subclinical congestion is frequent. Using biological
risk of death or rehospitalization in a proof-of- biomarkers, implantable hemodynamic monitoring,
concept study (30). However, this strategy, as and/or lung bioimpedance monitoring in selected
acknowledged previously by our group, has yet to be patients could easily identify patients with subclinical
validated in a randomized clinical trial. residual congestion who might benefit greatly from
JACC: HEART FAILURE VOL. 6, NO. 4, 2018 Girerd et al. 281
APRIL 2018:273–85 Assessing Congestion in Patients With HF

intensive treatment optimization. Importantly, Clinical signs and symptoms that can be easily
identifying congestion could trigger an increase in monitored in the community setting include heart
dosages of life-saving therapy (angiotensin-converting rate, blood pressure, weight, dyspnea, and edema.
enzyme inhibitors, beta-blockers, mineralocorticoid Biomarkers such as BNP and/or NT-proBNP and plasma
receptor antagonists), diuretics, and/or nitrates. volume status could also be obtained. Once collected,
Higher diuretic doses needed to alleviate congestion these data could then be incorporated into either
might activate the renin-angiotensin-aldosterone sys- existing or new electronic disease management plat-
tem, which could contribute to the progression of HF. forms. The value of home-based fingerstick testing for
However, analyses adjusted for congestion variables BNP and/or NT-proBNP has been suggested, although
usually result in a neutral association between diuretic more prospective studies are needed.
dose and outcome (33), which suggests that a higher Telemedicine is likely to be the most useful and
degree of congestion, rather than the diuretic dose it- scalable solution to implement network manage-
self, is harmful to HF patients. ment. However, several randomized trials have re-
The GUIDE-IT (Guiding Evidence Based Therapy ported neutral association of remote monitoring with
Using Biomarker Intensified Treatment) trial, which outcome, including the BEAT-HF (Better Effective-
also prioritized an increase of titration of neurohor- ness After Transition-Heart Failure) trial (36).
monal antagonists over diuretics (i.e., it was not Importantly, a Cochrane meta-analysis recently pro-
primarily focused on congestion relief) in patients vided a comprehensive overview of the current
with high levels of NPs, provided neutral results (34). literature and reported that “telehealth leads to
The results of GUIDE-IT did not end the discussion similar health outcomes as face-to-face or telephone
regarding NT-proBNP-guided care, because the trial delivery of care” (37). Nonetheless, randomized evi-
demonstrated no significant difference in HF thera- dence is still insufficient to formally recommend the
pies in the NT-proBNP-guided arm, whereas those in systematic use of telemedicine in this setting.
the usual care arm were seen far more frequently Telemedicine may be a solution to reduce the gap
than usual (10 visits in 15 months). In total, both between the increase of the older adult population
study arms had comparable reductions in NT-proBNP living with complex, multimorbid conditions and the
during follow-up, which explained the lack of decreasing amount of available health services. Thus,
differences in outcome. Future studies that focus on in the future, patient-centered telemedicine could
stricter adherence to NT-proBNP–mandated drug probably play a key role in HF patient care, particu-
therapy adjustment, together with a more rational larly by avoiding (re)hospitalizations. Biomarkers
usual care approach are needed. Importantly, in the (and possibly volume biomarkers) could be of great
successful CHAMPION trial, hemodynamic conges- interest in this field, especially if point-of-care ser-
tion in the intervention group was treated with vices are developed and used at home by the patients
diuretics and/or nitrates (i.e., primarily focused on themselves (38). Likewise, pulmonary pressure data
congestion relief), which eventually alleviated derived from wireless devices could be incorporated
congestion and was translated into a lower risk of into these telemedicine modalities. A computer-
readmission, whereas diuretics and nitrates treat- based algorithm that incorporates the patient-
ment were less frequently changed in the control reported signs and symptoms and point-of-care
group. In addition, treatment changes were unrelated biomarker evaluation could greatly improve patient
to pulmonary pressure in the control group, which care through a telemedicine loop, which would
elicited a poor discrimination of clinical examination trigger alarms and lead to optimization of treatment.
alone (32,35). This could be managed by trained nurses and physi-
cians possibly via a call platform that is manned for
INTEGRATING THESE TOOLS INTO 24 h/7 days by emergency callout services.
HEART FAILURE NETWORKS: The economical viability of this approach remains
THE ROLE OF TELEMEDICINE to be evaluated. Focusing on high-risk populations
would be key to achieve the highest possible treat-
Although the validated clinical, radiological, and ment effect from this strategy. However, most of
biological tools discussed in the first section of the cost of HF care is currently focused of the cost of
this review might improve patient care both during hospitalizations; hence, a dedicated strategy to
pre-hospital admission and in the hospital setting, avoid HF hospitalization could consequently be
implementing these tools into community-based highly cost-effective. Our group recently quantified
disease management programs could also provide the cost-effectiveness of a classical HF management
tremendous improvement in patient outcome. program in a real-world, population-based setting
282 Girerd et al. JACC: HEART FAILURE VOL. 6, NO. 4, 2018

Assessing Congestion in Patients With HF APRIL 2018:273–85

and accordingly found that such a program could proBNP–guided HF care (which in large part is
decrease health costs through a greater decrease in dependent on treatment and prevention of conges-
HF hospitalization despite the extra cost related to tion) seems to be appear promising (40). However,
the program itself (39). The expected cost-efficiency the GUIDE-IT trial, which was expected to provide
of a telemedicine loop, which decreases human definitive evidence of the impact of NP-guided ther-
costs, is likely to be similar. apy on clinical outcome in high-risk patients with HF,
was terminated for futility and retrieved neutral
GAPS IN EVIDENCE AND UNMET NEEDS results for all considered outcomes (34). Importantly,
titration of neurohormonal antagonists over diuretics
Congestion is strongly associated with HF prognosis, was prioritized in GUIDE-IT; thus, this study did not
especially during and following AHF hospitalization. primarily target decongestion in patients with high
Detection, dynamic monitoring, and management of NP levels. In addition, although there were more
congestion could help improve HF management at all adjustments to therapy in the biomarker-guided
stages of the journey of the patient. group, neither doses of HF therapy nor the achieved
Congestion quantification using a standardized NT-proBNP concentrations were significantly
quantitative approach (e.g., the EVEREST clinical different between the treatment groups. Although
score and B-lines count) could represent a valuable this would likely decrease our confidence on the
management tool upon admission and during an AHF efficiency of management mainly or solely based on
hospitalization. In our view, LUS is a strong candidate repeated NP measurements, it did not, however,
to test these congestion-guided treatments because solve the question regarding the use of NP
of its strong association with outcome (3,23,30). One measurements within a multimodality strategy or
major aspect that will undoubtedly promote LUS the impact of a strategy based primarily on decon-
expansion is the need for early treatment (as early as gestion (as in the CHAMPION trial) guided with
1 h) after admission to the emergency department as NT-proBNP.
emphasized in the current European Society of Car- There is strong evidence to support the risk-
diology guidelines for the management of AHF (6,27). stratifying properties of residual congestion at
The strong association of early treatment using discharge for AHF hospitalizations. However,
intravenous loop diuretics with lower in-hospital congestion assessed at the beginning (21) or during
mortality supports this recommendation (27). LUS (19) hospitalization for AHF is also strongly associated
could represent the key practice-changing tool that with outcome. To strengthen the case of congestion
would enable physicians to provide the right treat- as a therapeutic target, it would be useful to assess
ment (i.e., vasodilators and/or diuretics) to the right whether residual congestion is more, less, or equally
patients (i.e., patients with AHF) as quickly as prognostic than initial congestion. Such an analysis
possible. In addition, the swift AHF diagnosis that can would support that residual congestion is not simply
be achieved by LUS could allow patients to be triaged a marker for the severity of illness.
to the most appropriate facilities (cardiology ward or
intensive care unit with cardiovascular focus) almost A ROADMAP FOR THE CLINICAL
immediately after the first medical contact. During VALIDATION OF CONGESTION VARIABLES
the hospital stay, daily LUS could also guide diuretic AS ACTIONABLE BIOMARKERS
and/or vasodilator therapy and optimize the timing of FOR HF MANAGEMENT
discharge (30). The impact of LUS-guided AHF man-
agement at every step of the AHF hospitalization will As already emphasized, established tools such as
ultimately need to be tested in specific randomized biomarker measurement and echocardiography,
clinical trials. which are currently used to guide treatment de-
At post-discharge and in ambulatory HF patients, cisions, did not require evidence of improvement in
aside from the randomized evidence from the outcomes for their use to be approved (41). Concur-
CHAMPION trial (1), there is little evidence that HF rently, none of the congestion variables were suffi-
management guided by standardized congestion ciently validated to be considered as a Class I, Level of
assessment strategies is associated with better prog- Evidence: A, actionable biomarker to guide conges-
nosis. Thus, pulmonary artery pressure–guided HF tion treatment. However, NPs do have a class I
management should be considered in selected pa- recommendation for HF identification, mostly for
tients, similar to those studied in the CHAMPION their ability to detect left-sided congestion. Although
trial. NPs provide information relative to HF severity NPs provide the strongest evidence of congestion
as well as congestion, and BNP- and/or NT- variables, there is uncertainty regarding the best
JACC: HEART FAILURE VOL. 6, NO. 4, 2018 Girerd et al. 283
APRIL 2018:273–85 Assessing Congestion in Patients With HF

F I G U R E 2 Current and Future Framework for Congestion Detection

BP ¼ blood pressure; HF ¼ heart failure.

strategy to use in NP-guided therapy in clinical lasted for 48 h, and treatment was not tailored to the
practice. Overall, much of the literature on conges- congestion phenotype (including hemodynamic
tion consists of observational data. congestion) of patients admitted with AHF. In addi-
One limitation of some of the congestion trials was tion, the CHAMPION trial, which monitored and
the absence of a strictly defined therapeutic strategy subsequently acted on congestion during a longer
that was applied according to biomarker results. In period of time, was successful. From our point of
contrast with most trials in this field, the CHAMPION view, it is likely that future successful AHF trials
trial used a strict therapeutic algorithmic strategy would not use decongestion therapies equally,
according to congestion assessments (1), which might regardless of the congestion profile, but would
be one of the factors that led to the success of this instead constitute genuine congestion-guided treat-
trial. Interinvestigator management practice vari- ment trials that use specifically defined individual-
ability could be a major source of “noise” within trials ized therapeutic algorithms triggered by
that could be reduced by implementing protocol- individualized biomarker or clinical assessment tar-
specified management strategies for treating gets according to the clinical context. This hypothesis
congestion. is appealing, although extensive work is needed to fill
Importantly, 2 recently published trials that in the gaps in evidence with regard to optimal
investigated the effect of vasodilator treatment, the decongestion therapy, especially in the aftermath of
TRUE-AHF (Efficacy and Safety of Ularitide for the the results of TRUE-AHF and RELAX-AHF2. From our
Treatment of Acute Decompensated Heart Failure) standpoint, there is a need for a trial that tests a
(42) and RELAX-AHF 2 (Efficacy, Safety and Tolera- personalized algorithm, in contrast to the strategy
bility of Serelaxin When Added to Standard Therapy used in TRUE-AHF and RELAX-AHF 2, which were
in AHF) (43) trials, provided neutral results. These based on LUS and echographic biomarkers of
results greatly hampered the concept of reaching congestion during the hospital stay in patients with
better mid-term outcome by a better and/or smarter AHF. In these trials, as in the CHAMPION trial, a
treatment of congestion during the early hospitali- management algorithm personalized to the clinical
zation period. Notwithstanding the latter, it should setting would guide investigator intervention,
be acknowledged that in both trials, interventions thus decreasing interinvestigator variability, and
284 Girerd et al. JACC: HEART FAILURE VOL. 6, NO. 4, 2018

Assessing Congestion in Patients With HF APRIL 2018:273–85

ultimately ensuring that the information leads to results, and may be a practice-changing tool in the
appropriate interventions. These individualized pre- and in-hospital management of patients with
novel strategies have the potential to answer many AHF.
lingering questions related to congestion-based Telemedicine, although currently underdeveloped,
treatment of acute and post-acute worsening HF. could represent the cornerstone for out-of-hospital
From our standpoint, a need for a trial at the initial monitoring of patients with HF by mostly using a
stage of AHF management still remains, when diag- combination of self-reported clinical congestion var-
nostic uncertainty is often still present. The use of iables and point-of-care biological data.
LUS has been successfully explored for triage in pre- The CHAMPION trial convincingly showed that
hospital pilot studies (44), but its use within the treating hemodynamic congestion, mostly by opti-
first minutes of acute dyspnea management is not yet mizing diuretics and nitrates, results in better patient
commonplace, at least in Europe. We advocate for a outcomes (1,35). In patients who do not have wireless
randomized trial to investigate the impact of early pulmonary artery hemodynamic monitoring (as used
LUS on clinical outcome in patients with acute dys- in the CHAMPION trial), it appears suboptimal to
pnea. Improving the certainty in early diagnosis of guide treatment based only on clinical consider-
congestion due to AHF would enable rapid imple- ations. These patients could benefit from a multipa-
mentation of treatments for AHF worldwide, and rameter approach to detect signs of congestion,
potentially translate into improved outcomes that are including clinical evaluation, biological biomarkers,
direly needed in this group of patients. and ultrasound, to improve outcome and reduce re-
hospitalizations. The framework in which these
CONCLUSIONS tools could operate in detecting congestion is shown
in Figure 2.
Evaluating congestion in HF is as complex as it is
ACKNOWLEDGMENTS Medical writing support was
crucial, and its timely and effective treatment can
provided by Amy Whereat for Matrix Consultants and
improve outcome (35). Because of the importance of
funded by an unrestricted grant from Novartis Phar-
congestion in HF, we and others (32), recommend
maceuticals (Bâle, Switzerland). The authors also
that assessments extend beyond basic clinical evalu-
thank Wendy Gattis Stough and Erwan Bozec for the
ations. The currently available various tools need to
editing of the paper.
be applied in a coherent and effective manner within
each stage of the patient management cycle.
We recommend the use of the EVEREST clinical ADDRESS FOR CORRESPONDENCE: Prof. Patrick
score in most nonemergency situations. NPs (already Rossignol, Centre d’Investigations Cliniques-
widely used), together with estimated plasma volume INSERM CHU de Nancy, Institut lorrain du Cœur
variables (almost never used), can be useful to et des Vaisseaux Louis Mathieu, 4 rue du
repeatedly assess congestion throughout the patient Morvan, 54500 Vandoeuvre Lès Nancy, France.
management cycle. LUS is easy to use, provides rapid E-mail: [email protected].

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