Transthoracic Impedance Accurately Estimates Pulmonary Wedge Pressure in Patients With Decompensated Chronic Heart Failure


Gabriella Malfatto, MD, PhD, Divisione di Cardiologia, Istituto Scientifico Ospedale San Luca, Piazzale Brescia, 20-20149 Milan, Italy


Routine cardiac catheterization to assess pulmonary capillary wedge pressure (PCWP) is not recommended in heart failure (HF), and various noninvasive tools have been proposed. The authors evaluated the reliability of echocardiography, brain natriuretic peptide (BNP), and thoracic electrical bioimpedance (TEB) in predicting PCWP in 29 patients (72±4 years, New York Heart Association class 3.5±0.9, ejection fraction 28%±6%) who underwent hemodynamic evaluation for worsening HF. Echocardiography was performed immediately before the hemodynamic study. During clinical stability, PCWP, plasma BNP, and TEB were simultaneously assessed. Among TEB variables, thoracic conductance (thoracic fluid content [TFC]=1/kΩ) was used. PCWP was related with E/E′ obtained with mitral Doppler and mitral annulus tissue Doppler imaging echocardiography ( R=0.55, P<.005), with BNP levels (R=0.43, P<.01) and TFC values (R=0.69, P<.001). For detection of PCWP ≥15 mm Hg, TFC ≥35/kΩ had high specificity (97%) and sensitivity (86%) and negative (92%) and positive (97%) predictive value, while E/E′ and BNP levels had poorer specificity. After infusion of the inodilator levosimendan, changes in TFC and PCWP were of the same order of magnitude and mutually related. In worsening HF, TEB could help avoid right heart catheterization, since it may estimate PCWP better than BNP or echocardiography. Moreover, TFC could be used for noninvasive assessment of drugs’ effect. Congest Heart Fail. 2012;18:25–31. ©2011 Wiley Periodicals, Inc.

In patients with heart failure (HF), symptoms and signs of congestion profoundly affect quality of life and survival1 and are important targets for therapy, since their early identification and treatment may prevent hospitalizations, slow the progression of the disease, and possibly affect prognosis.2–4 However, focus on only physical signs may often lead to overlooked pulmonary congestion.5 The gold standard for pulmonary congestion estimate is pulmonary capillary wedge pressure (PCWP) assessment obtained through cardiac catheterization, a procedure that is currently not recommended for routine evaluation of HF patients.6 Noninvasive techniques used as surrogates of PCWP measurement7–10 carry inherent shortcomings, such as radiation exposure in the case of chest x-ray, high cost, or the need for expert operators for ultrasound examination. Moreover, the value of echocardiography has recently been questioned in some subsets of patients.11 In the past few years, bedside assessment of brain natriuretic peptide (BNP) levels has been proposed as a screening tool for the severity of the disease in patients with acute HF, due to its reported relationship with PCWP in some studies.12–15 Another tool for noninvasive hemodynamic evaluation may be the analysis of thoracic electrical bioimpedance (TEB),16–18 but its reliability is controversial19 and may depend on the clinical setting in which it is employed (ie, acute vs chronic HF).20

This study was carried out in patients with worsening advanced chronic HF21 with a 2-fold purpose. First, we explored the reliability of TEB measurement in predicting PCWP both at rest and after hemodynamically tailored treatment. Moreover, we investigated whether echocardiography and BNP assessment would add further information with respect to bioimpedance regarding pulmonary congestion as estimated by PWCP.


Study Population

From September 2009 to December 2010, 45 consecutive patients with advanced systolic HF were scheduled for hemodynamic evaluation to guide further treatment because of worsening of symptoms and clinical status despite optimal therapy. Of these, 29 patients (64%) met the entry criteria. We excluded patients presenting with any condition that would interfere with BNP assay, electrical bioimpedance determination, or echocardiography examination: relevant overweight (body mass index [BMI] >35), severe chronic obstructive pulmonary disease, severe renal failure (creatinine clearance ≤25 mL/min), atrial fibrillation, moderate to severe aortic regurgitation, pleural or pericardial effusion, body weight <50 kg and >120 kg, and left ventricular aneurism repair. Clinical characteristics of the patients are shown in Table I. We did not modify patients’ usual treatment during data collection. Eventually, the results of the hemodynamic study led to a change in drug regimen. Data were collected within a short timeframe of about 30 minutes, with the following sequence: echocardiography, BNP assessment, invasive hemodynamic assessment in the intensive care unit, and thoracic bioimpedance. Investigators who performed a given test were unaware of the results of the other ones. In 9 patients in whom hemodynamic evaluation was performed also after inotropic treatment, the sequence of tests was repeated immediately before the last measurement of PCWP and removal of Swan-Ganz catheters. Characteristics of these patients are shown in Table II.

Table I.   Demographic and Clinical Characteristics of the Study Population (n=29)
  1. Abbreviations: ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; BMI, body mass index; BNP, brain natriuretic peptide; E/E′, ratio between velocity of the E and A wave on Doppler transmitral flow; EF, ejection fraction; eGFR, estimated glomerular filtration rate; EROA, effective regurgitant orifice area; ICD, implantable cardioverter-defibrillator; LVEDV, left ventricular end-diastolic volume; MAP, mean arterial pressure; NYHA, New York Heart Association; PAP, estimated systolic pulmonary pressure; TFC, thoracic fluid content.

Age, y72±4
Sex, male/female, No.22/7
Ischemic/nonischemic, No.17/12
NYHA class3.5±0.09
MAP, mm Hg88±9
eGFR Cockroft’s formula, mL/min60.8±11.2
 EF, %28.1±5.9
 LVEDV, mL187±47
 Functional mitral regurgitation, any degree, No. (%)25 (8)
 Significant mitral regurgitation, EROA >20 mm2, No. (%)11 (36)
 PAP, mm Hg47.1±13.6
 Restrictive/pseudonormal filling pattern, No. (%)20 (71)
BNP, pg/mL570±225
TFC, 1/kΩ42.2±7.0
ICD±biventricular pacing, yes/no, No.20/8
Pharmacologic treatment, %
 ACE inhibitors91
 Loop diuretics70
Table II.   Demographic and Clinical Characteristics of Patients Treated With Levosimendan (n=9)
  1. Abbreviations: ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; BMI, body mass index; BNP, brain natriuretic peptide; E/E′, ratio between velocity of the E and A wave on Doppler transmitral flow; EF, ejection fraction; eGFR, estimated glomerular filtration rate; EROA, effective regurgitant orifice area; ICD, implantable cardioverter-defibrillator; LVEDV, left ventricular end-diastolic volume; MAP, mean arterial pressure; NYHA, New York Heart Association; PAP, estimated systolic pulmonary pressure; TFC, thoracic fluid content.

Age, y74±5
Sex, male/female, No.7/2
Ischemic/nonischemic, No.6/3
NYHA class3.6±0.06
MAP, mm Hg89±9
eGFR Cockroft’s formula, mL/min56.7±9.3
 EF, %25.8±7.5
 LVEDV, mL195±47
 Functional mitral regurgitation any degree, No. (%)9 (100)
 Significant mitral regurgitation, EROA >20 mm2, No. (%)9 (100)
 PAP, mm Hg49.4±16.1
 Restrictive/pseudonormal filling pattern, No. (%)9 (100)
BNP, pg/mL686±175
TFC, 1/kΩ45.6±5.5
ICD±biventricular pacing, yes/no, No.8/9
Pharmacologic treatment, %
 ACE inhibitors100
 Loop diuretics100

Transthoracic Echocardiography

Echocardiographic examination, including Doppler and tissue Doppler imaging analysis, was performed immediately before the hemodynamic study according to recommendations of the American Society of Echocardiography.22 Pulsed Doppler was used to record transmitral and pulmonary venous flow in the apical 4-chamber view.23 Tissue Doppler velocities were acquired at the septal and lateral annular sites as previously described.18,24 Mitral inflow measurements included peak early (E) and peak late (A) velocities, E/A ratio, and deceleration time of E velocity. For pulmonary venous flow, measurements included peak systolic, diastolic, atrial reversal (Ar) velocities, systolic filling fraction, and duration of Ar. The early diastolic (E′) velocity by tissue Doppler imaging at the septal and lateral annular sites was measured. The E/E′ ratio was calculated from the average of septal and lateral E′ because this approach has been shown to yield optimum accuracy in patients with regional wall motion abnormalities.24 We present data on E/E′ only, since this is the variable most frequently compared with PCWP and BNP values.7,8,11 Moreover, the analysis of the complex relationship of diastolic function with filling pressures was beyond the purpose of the study.


Plasma BNP levels were assessed by a point-of-care system based on fluorescence immunoassay (Triage BNP Test; Biosite Inc, San Diego, CA) at least 30 minutes after Swan–Ganz catheter insertion.18

Hemodynamic Protocol

Swan–Ganz catheters were positioned in the main pulmonary artery and confirmed by chest radiography. Hemodynamic data, including systemic blood pressure, central venous pressure, and PCWP (wedge position was verified by fluoroscopy and phasic changes in pressure waveforms), represent the average of 5 cycles with balanced transducers (0 level at the midaxillary line). Central venous pressure and PCWP were assessed at end expiration with a balloon-tipped catheter at steady state with the patient in a supine position. The hemodynamic goals and pharmacologic approach to intravenous therapy in our HF intensive care unit followed usual guidelines: optimal hemodynamic response was defined as a decrease in PCWP to values lower than 15 mm Hg, a decrease in central venous pressure to values <8 mm Hg, and an improvement in cardiac index up to at least 2.2 L/min/m2 while maintaining mean arterial pressure >65 mm Hg. We report the results obtained with the inodilator levosimendan (24-hour infusion of 0.2 mg/kg/min, no bolus) in 9 patients in whom the concomitant β-blocking treatment was maintained.25

Electrical Bioimpedance

Thoracic bioimpedance was performed in all patients by the same operator using equipment with identical software (BioZ ICG Monitor, CardioDynamics, San Diego, CA; BioZed, NICCOMO, Germany).26 Four dual impendance cardiography (ICG) sensors were placed: two at the base of the neck under each ear, and two on either side of the chest, in the mid-axillary line at the level of the xyphoid. A cable with 8 ICG lead wires was attached to the sensor sites. The cuff of an integrated validated oscillometric blood pressure–measuring device cuff was connected to the patient’s arm. The recording was performed for 10 minutes, and an average ICG status report was stored for analysis. Variables evaluated in this study have been described previously and include measurements of cardiac blood flow, vascular resistance, fluid status, and indices of electromechanical timing and contractility.26,27 The present study aimed at evaluating an index of pulmonary congestion; therefore, we report on thoracic conductance, ie, the inverse of thoracic impedance, as representative of total fluid volume in the chest (thoracic fluid content TFC=1/Z0*1000=1/kΩ).18

Statistical Analysis

Data are expressed as mean±1 standard deviation. To correlate data variables, we used linear regression analysis, performed with a least square commercial fitting routine (OriginPro 7.0, Microcal, Northampton, MA). For the first aim of the study, we correlated values of PCWP with TFC values. For the second aim of the study, we correlated values of PCWP with E/E′ values and BNP levels, respectively. The effect of levosimendan infusion on continuous variables was examined by paired t test, while the effect on discrete variables was not considered because of the small number of observations that did not allow a comparison by chi-square test. A P<.05 was considered as the minimum level of statistical significance. Finally, receiver-operating characteristic (ROC) curves were constructed to determine optimal sensitivity and specificity of the different variables and of their combinations in assessing patients’ hemodynamic status. In so doing, we first analyzed individual data of the 29 patients, each represented by a single value. However, even if a significant relationship was found among different variables, data were narrowly distributed in the pathological range (ie, PCWP was >20 mm Hg in all patients). To obtain a number of data encompassing the widest range of study variables, we then pooled all measurements and repeated the analysis. Thus, 38 data points were obtained (9 patients who underwent levosimendan infusion contributed to the data set with two observations).


Baseline Predictors of the Hemodynamic Picture

The analysis of the hemodynamic picture offered by invasive and noninvasive measurements for all data points (as detailed above, we present 38 observations in 29 patients) showed that a significant relationship was present between PCWP and TFC values (R=0.69, P<.001), BNP levels (R=0.43, P<.01), and E/E′ obtained with Doppler and tissue Doppler imaging echocardiography (R=0.55, P<.005) (Figure 1). The latter three indexes were also mutually related (P<.001).

Figure 1.

 Relationship between measured values of pulmonary capillary wedge pressure (PCWP) and thoracic fluid content (TFC) values (panel A), brain natriuretic peptide (BNP) levels (panel B), and ratio between velocity of the E and A wave on Doppler transmitral flow (E/E′) (panel C). Results from 38 observations obtained in 29 patients are presented.

Keeping in mind our purpose of identifying patients with PCWP ≥15 mm Hg, we obtained the highest specificity (94%) and sensitivity (86%) by using thoracic bioimpedance. Indeed, a TFC ≥35/kΩ could identify patients with PCWP ≥15 mm Hg with high negative (92%) and positive predictive value (97%). The use of either E/E′≥15 or BNP values ≥350 pg/mL for the same goal also showed good sensitivity (93% and 91%, respectively), but yielded a poorer specificity (50% and 67%, respectively), as shown by ROC curves in Figure 2.

Figure 2.

 Receiver-operating curves representing sensitivity and specificity of selected cutoff values of thoracic fluid content (TFC) (curve A), brain natriuretic peptide (BNP) (curve B), and ratio between velocity of the E and A wave on Doppler transmitral flow (E/E′) (curve C) for the correct diagnosis of pulmonary capillary wedge pressure ≥15 mm Hg.

When combining two indexes, the combination of BNP ≥350 pg/mL and TFC ≥35/kΩ identified patients with PCWP ≥15 mm Hg with better specificity (98%), sensitivity (94%), negative predictive value (96%), and positive predictive value (97%) than associating TFC and E/E′ values. Finally, E/E′≥15 combined with BNP ≥350 pg/mL had specificity and sensitivity similar to those of TFC ≥35/kΩ alone (96% and 88%, respectively).

Evaluation of the Response to Drugs

In 9 patients, the hemodynamic evaluation was repeated after 24-hour infusion of the inodilator drug levosimendan. As shown in Table III, levosimendan significantly reduced PCWP, E/E′, BNP levels, and TFC. Moreover, we observed a trend toward an improvement in transmitral filling pattern and a reduction in the severity of mitral regurgitation. Of note, changes in TFC and PCWP were of the same order of magnitude and significantly related (Figure 3).

Table III.   Acute Effects of Levosimendan on Study Variables
 BeforeAfterP Value (t Test)
  1. Abbreviations: BNP, brain natriuretic peptide; E/E′, ratio between velocity of the E and A wave on Doppler transmitral flow; EF, ejection fraction; HR, heart rate; MAP, mean arterial pressure; PAP, estimated systolic pulmonary pressure; PCWP, pulmonary capillary wedge pressure; TFC, thoracic fluid content. aNo statistical analysis was performed due to the small number of observations.

MAP, mm Hg89±992±11.21
HR, beats per min72±876±10.13
EF, %25.8±7.530.4±6.6<.05
PAP, mm Hg49.4±16.135.6±12.2<.05
Restrictive/pseudonormal filling pattern, No. (%)9 (100)3 (33)a
Moderate/severe functional mitral regurgitation, No. (%)9 (100)4 (42)a
PCWP, mm Hg30.6±5.919.1±6.5<.01
BNP, pg/mL686±175293±122<.01
TFC, 1/kΩ45.6±5.536.9±4.0<.01
Figure 3.

 Relationship between changes in pulmonary capillary wedge pressure (PCWP) and thoracic fluid content (TFC) (expressed as percentage change from baseline values) induced by a 24-hour infusion of levosimendan in 9 patients.


In advanced HF, dyspnea is often the predominant symptom: its presence points to pulmonary congestion, which, in turn, is related to volume overload.1 Since the direct measurement of hemodynamics in these patients is limited by its invasiveness, noninvasive techniques represent attractive options. Among them, biomarkers, echocardiography, and transthoracic impedance cardiography have received attention due to their relationship with invasively measured estimates of filling pressures in several studies.7–10,12–18 However, evidence challenging the use of these indexes has also been provided.11,19

For instance, even if E/E′ value was included by an expert panel in an algorithm for the noninvasive diagnosis of diastolic HF,28 in patients with severe cardiac dysfunction, enlarged left ventricles and worsening clinical status, tissue Doppler–derived mitral E/E′ ratio alone was not reliable in predicting intracardiac filling pressures assessed with PCWP.11 Indeed, E/E′ (similar to most echocardiographic indexes of diastolic function) reflects both load-dependent and load-independent diastolic effects29: when ventricles are enlarged and fibrotic, an irreversible, load-independent diastolic dysfunction may prevail, leading to an inaccurate estimate of filling pressures by this echocardiographic index. Our study dealt with patients in whom, despite severe cardiac dysfunction and worsening clinical status, only a moderate enlargement of the ventricles was present. This would explain, despite the low specificity, the fair relationship between E/E′ and PCWP and the good sensitivity of E/E′≥15 in detecting elevated PCWP.

Plasma BNP identified high PCWP with good sensitivity but with the lowest specificity. This is not surprising, because BNP levels show a large amount of variability among patients for a variety of reasons, including differences in renal function, age, and body weight.30 Some of these potential confounding factors were in fact considered, since we did not include in this study obese patients or patients with severe renal failure. Nonetheless, while in the presence of relatively low BNP values (ie, <350 pg/mL), we may rule out the presence of a relevant congestion, higher values (especially for BNP values >400 pg/mL) may not be of help in the individual patient. Furthermore, BNP levels are susceptible to acute load changes, as in the case of the patients treated with levosimendan, in whom a reduction of the peptide levels followed the favorable hemodynamic effect of the drug. Such a finding seems to indeed confirm that changes in this parameter may accurately reflect changes in patients’ volume status.31

The potential role of noninvasive hemodynamic monitoring in patients admitted with advanced HF has recently been evaluated by the BioImpedance Cardiography in Advanced Heart Failure (BIG) study, conducted as part of the larger Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial.21 The results were rather dismal, because thoracic bioimpedance provided some information about cardiac output but was unrelated to left-sided filling pressures and bore no prognostic relevance. Since the BIG study was part of a multicenter trial, some variability in the performance of thoracic bioimpedance, or in its timing related to the hemodynamic evaluation, may have affected TFC evaluation. On the other hand, values of PWCP obtained during short-lasting hemodynamic studies may differ from those obtained at steady-state when patients’ cardiac and ventilatory reaction to catheter insertion was no longer present (as was the case in our study).


A limitation of the study could have been the selection of “ideal” patients, in whom no confounding problems were present (such as arrhythmias, very large ventricles, prosthetic valves, pleural or pericardial effusions, chronic obstructive pulmonary disease): this selection excluded about one third of potential candidates. In smaller studies carried out in less selected patients with systolic HF, the use of thoracic bioimpedance has provided conflicting results: either TFC was poorly correlated with invasively measured PCWP18 or the combination of a high TFC and low stroke volume index was associated with a higher LV end-diastolic pressure when compared with the combination of a low TFC and high stroke volume index.15 We did not measure LV end-diastolic or left atrial pressure, and we relied on PCWP as an accepted and validated surrogate. Finally, the small number of patients included, and the single-center origin of data, were other potential drawbacks of our study, which, however, was large enough to test our hypothesis and yield significant positive results.


Assessment of TFC by thoracic bioimpedance may reveal the presence of high filling pressure in patients with advanced HF better than E/E′ values or BNP levels. Indeed, adding BNP levels and E/E′ values in a stepwise approach slightly improved the predictive power of TFC values. A noninvasive approach to the analysis of the fluid status may possibly help in avoiding right heart catheterization in many patients. Finally, thoracic bioimpedance could also be useful in the follow-up of patients undergoing infusion of drugs modifying the hemodynamic status.


Acknowledgments:  We are grateful to Giovanni Stellacci, RN, Cesare Longo, RN, and Annalisa Frigi, RN, for help in performing catheterization studies and collecting hemodynamic data and to Ada Spiezia, RN, Cosetta Corapi, RN, and Ellen Tosazzi, PhD, for patients’ clinical management throughout the study.