Functional capacity and ventilatory efficiency assessed by cardiopulmonary exercise testing (CPET) are of established value in patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVDS)1,2. Functional capacity is generally determined by peak oxygen consumption (pVO2), while assessment of ventilatory efficiency is based on analysis of the relationship between minute ventilation (VE) and carbon dioxide (CO2) production - VE/VCO2 - or ventilatory equivalent for CO2, in practice the amount of air needed to eliminate one liter of CO2.

There are multiple determinants of functional capacity, particularly the interaction between pulmonary, cardiac and skeletal muscle function, as well as age, gender, muscle mass and conditioning status1. Despite this dependence on multiple factors, in fit individuals without pulmonary or skeletal muscle disease, pVO2 provides an indirect measure of cardiac output (CO), the correlation being determined by established formulas1,3,4.

Although the most important determinant of ventilatory efficiency is the correlation between ventilation and perfusion2, the mechanisms that lead to reduced efficiency in CHF patients remain the subject of debate5.

Thoracic electrical bioimpedance (TEB) was developed in the 1960s as part of NASA's space program6, as a non-invasive technique for continuous hemodynamic monitoring. It is based on the use of a high-frequency, low-amplitude electric current to calculate impedance of the flow of electricity through the chest. It measures instantaneous beat-by-beat changes in electrical impedance, on the basis of which algorithms have been developed to calculate parameters such as systolic volume, CO and thoracic fluid content (TFC), among others. The latest generation TEB systems are being used more widely following studies confirming their efficacy in various pathologies and correlation with invasive measurements7–9.

TFC, a new parameter assessed non-invasively by TEB, is an indicator of total chest fluid volume, both intra- and extracellular, particularly in the lungs10. In the absence of significant pleural and/or pericardial effusion, it can be used as an indirect measure of pulmonary perfusion.

The aim of this study was to investigate the possible correlation between parameters of ventilatory efficiency obtained by CPET and TFC assessed by TEB, in patients with CHF due to LVSD.

We studied 120 patients with LVSD and CHF, 91 (76%) male, 76 (63%) of non-ischemic and 44 (37%) of ischemic etiology, referred to our laboratory for a first CPET.

Only patients with left ventricular ejection fraction (LVEF) ≤40% on echocardiographic study in the previous 30 days were included; patients in New York Heart Association (NYHA) functional class IV and those with diseases that limited their ability to exercise or with moderate to severe lung, kidney or liver disease were also excluded. The presence of moderate or severe lung disease was assessed mainly through clinical history, observation and chest X-ray; only 24 patients (20%) underwent spirometry, which showed no significant alterations.

The patients' mean age was 52.1 ±12.1 years (21–77), body mass index 26.4±4.1 kg/m2 (17.6-37.6), left ventricular (LV) end-diastolic dimension 39.5±5.8 mm/m2 (31.9-57.0) and echocardiographic LVEF 27.5±8.0% (10-40%), and 83% were in sinus rhythm. According to the records of the physicians referring for CPET, 80.8% of the patients were in NYHA functional class ≤II. Mean serum creatinine was 1.10±0.40 mg/dl (0.6-2.0), hemoglobin 13.7±1.5 g/ dl (10.9-17.5), and NT-proBNP 2163.5±2387.8 pg/ml (54.8-10,924.0). With regard to medication, 96% were taking angiotensin-converting enzyme inhibitors and/ or angiotensin receptor blockers, 89% furosemide and/ or thiazide, 79% beta-blockers, 68% spironolactone, and 45% digoxin, and 20% were treated with a cardiac resynchronization device. The characteristics of the study population are summarized in Table.

TFC ranged between 20.6 and 45.8 kOhm-1, mean 32.2, SD 5.7, median 32.7. The values for the CPET parameters analyzed were: pVO2 8.9-40.6 ml/kg/min, mean 21.0, SD 6.2, median 20.2; VE/VCO2 slope 19.8-60.7, mean 30.7, SD 7.9, median 29.1; and VE/VCO2 at AT 21–62, mean 33.1, SD 7.5, median 31.5.

By linear regression, there was a strong correlation between CPET parameters: pVO2 and VE/VCO2 slope - r=0.64, p <0.001; pVO2 and VE/VCO2 at AT - r=0.66, p <0.001; and VE/VCO2 slope and VE/VCO2 at AT - r=0.88, p <0.001.

TFC did not correlate with pVO2 (r=0.05, p=0.58), but showed correlation with parameters of ventilatory efficiency: r=0.20, p=0.032, r2=0.04 for VE/VCO2 slope and r=0.25, p=0.009, r2=0.06 for VE/VCO2 at AT (Figure 1).

Figure 1.

A: correlation between TFC and VE/VCO2 slope; B: correlation between TFC and VE/VCO2 at AT (abbreviations as in text).

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ROC curves were used to assess the quality of the correlations between TFC determined by TEB and ventilatory parameters by CPET. For VE/VCO2 slope ≥34, the AUC was 0.70, with 95% confidence interval (CI) of 0.59-0.81 (Figure 2). TFC >35.9 had sensitivity of 60% and specificity of 80% for VE/VCO2 ≥34. For VE/VCO2 at AT ≥34, the AUC was 0.74, with 95% CI of 0.65-0.84 (Figure 2). TFC >34.9 had sensitivity of 65% and specificity of 84% for VE/VCO2 at AT ≥34.

Figure 2.

ROC curves - A: TFC vs. VE/VCO2 slope; B: TFC vs. VE/VCO2 at AT (abbreviations as in text).

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The present study found a correlation, albeit of low statistical significance, between resting TFC and CPET parameters assessing ventilatory efficiency. TFC can be used as an indirect measure of pulmonary perfusion; a previous study by our group established a significant correlation between TFC and pulmonary capillary wedge pressure (PCWP)9. These results are in agreement with those of Reindl et al.12, who demonstrated a positive correlation between resting PCWP and pulmonary artery pressure and VE/VCO2 slope.

Lewis et al.5 also found a significant correlation between resting PCWP and VE/VCO2 slope. Chronically elevated left ventricular filling pressures may contribute to inadequate pulmonary vasodilation and a high dead space-to-tidal volume ratio (VD/VT) during exercise through pulmonary vascular remodeling. On the other hand, no correlation was seen between VE/VCO2 slope and PCWP during exercise, suggesting that ventilatory efficiency is not dictated simply by acute changes in left ventricular filling pressures during exercise; for these authors, changes in pulmonary vasomotor tone and right ventricular function may also be important determinants of ventilatory efficiency in patients with CHF.

The role of muscle ergoreceptor overactivity in hyperventilation during exercise in CHF patients has also been investigated13–15. The ergoreflex, which is heightened in these patients, is a complex metabolic reflex in which peripheral chemoreceptors in muscle react to local metabolic byproducts during exercise and initiate a neural reflex that drives hyperventilation5. Although the relative contribution of the ergoreflex to this phenomenon remains to be fully clarified, Guazzi et al.16 have demonstrated that long-term use of sildenafil in CHF patients attenuates this reflex and improves VE/VCO2 slope.

To summarize, many different factors determine ventilatory efficiency in patients with CHF. The present study demonstrated that it correlates with TFC as assessed by TEB, and we postulate that the value of this new parameter is not restricted to its correlation with PCWP. TFC, a measure of the total volume of chest fluids, both extra- and intracellular, provides better and more reliable assessment of changes than traditional hemodynamic parameters10. Okawa et al., in a study of patients with acute myocardial infarction, also found a significant correlation between TFC and PCWP, which was independent of cardiac index17. However, their results suggest that TFC is a better predictor of the degree of pulmonary congestion, particularly when PCWP is <18 mmHg.

Our aim was to investigate the possible correlation between TFC assessed by TEB and parameters of ventilatory efficiency determined by CPET. However, we also analyzed pVO2, and in the TEB studies performed prior to CPET, cardiac output was also determined. While as expected, pVO2 presented a strong correlation with ventilatory efficiency parameters, no significant correlation was found with TFC, suggesting that this is not a determinant of pVO2. Resting CO assessed by TEB showed a mean value of 4.5±1.2 l/min (1.9-8.1). No significant correlation was found between CO and TFC (r=0.156, p=0.10), nor with VE/ VCO2 slope (r=0.169, p=0.07) or VE/VCO2 at AT (r=0.118, p=0.23), the correlation being significant only with pVO2 (r=0.208, p=0.023). While not within the scope of the present study, these results support the idea that CO, even assessed at rest, is a determinant of pVO21,3,4.

Most studies investigating correlations between hemodynamic parameters, obtained either invasively or non-invasively, and functional capacity and ventilatory efficiency assessed by CPET, have been based on analysis of hemodynamic parameters at rest. Interestingly, when these parameters are assessed during exercise, either they do not correlate with CPET variables (with the exception of pVO2 and CO)5, or they provide no additional prognostic value1. This surprising finding may be explained by the fact that there are multiple determinants of CPET parameters, including cardiac reserve and skeletal muscle, pulmonary and endothelial (dys)function. The correlation between ventilatory efficiency determined by VE/VCO2 slope and hemodynamic variables assessed at rest would appear less controversial, since it is constant at submaximal exercise.

The main limitations of the present study are that spirometry was not performed and that changes in TFC during exercise were not assessed.

Thoracic fluid content determined by thoracic electrical bioimpedance correlates with CPET parameters of ventilatory efficiency in patients with congestive heart failure due to left ventricular systolic dysfunction, suggesting that it may be one of its determinants.

The authors have no conflicts of interest to declare.