WITHDRAWN: Peripheral Venous Pressure Measurements to Evaluate Congestion in pulmonary arterial hypertension

doi:10.21203/rs.3.rs-5251665/v1

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WITHDRAWN: Peripheral Venous Pressure Measurements to Evaluate Congestion in pulmonary arterial hypertension

https://doi.org/10.21203/rs.3.rs-5251665/v1

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Background

Right atrial pressure (RAP) is an important prognostic criterion in pulmonary hypertension (PH). Elevated mean RAP measured by cardiac catheterization is an independent risk factor for mortality. Accurate bedside assessment of congestion in the management of patients with PH remains challenging. As a continuous conduit of circulating fluid, systemic congestion represented by high RAP may be reflected by peripheral venous pressure (PVP). We evaluated the reliability of PVP measurements for assessing congestion beyond conventional clinical assessments.

Methods

We performed conventional congestion assessments and PVP measurements in 138 patients undergoing right heart catheterization. PVP was measured via the 22-gauge peripheral venous access placed in the upper extremity.

Results

The mean RAP and PVP were 8.7 ± 4.2 mmHg and 10.7 ± 4.3 mmHg, respectively. PVP exhibited a strong linear correlation with RAP (Pearson r = 0.839; p < 0.001). PVP demonstrated significant discriminatory power for both RAP < 8 mmHg (area under the curve [AUC]: 0.91 [95% confidence interval: 0.86–0.96]; sensitivity: 72%; specificity: 94% cut-off: 8.5mmHg) and RAP ≥ 12 mmHg (AUC: 0.92 [0.87–0.97]; sensitivity: 82%; specificity: 89% cut-off: 12.5mmHg).

Conclusions

PVP measured via peripheral venous access strongly correlates with invasively obtained RAP. PVP measurements may improve current bedside assessments of congestion.

cardiac catheterization

peripheral venous pressure

right atrial pressure

systemic congestion

Pulmonary arterial hypertension is a progressive disease of proliferative and fibrotic changes of the pulmonary vasculature (1). PAH progressively causes decreased pulmonary vascular compliance, increased pulmonary vascular resistance (PVR), right ventricular failure, and ultimately death (1). Diagnosis of PAH is based on systematic hemodynamic measurements of the right heart and pulmonary circulation obtained by right-sided heart catheterization. Due to the risk of complications and invasiveness, right-sided heart catheterization is limited in the longitudinal evaluation of patients with PAH (1).

Right atrial pressure (RAP) is an essential component in the hemodynamic assessment of patients and a requisite for the noninvasive estimation of pulmonary artery pressures (2). RAP provides an estimation of intravascular volume, which is a critical component for optimal patient care and management (2). Elevated mean right atrial pressure (RAP) measured by RHC is an established risk factor for poor survival in the Registry to Evaluate Early and Long-term PAH Disease Management as well as other cohorts (3–6). Although the gold standard for RAP evaluation is invasive monitoring, various techniques are available for the noninvasive evaluation of RAP (2). Various echocardiographic methods have been suggested for the evaluation of RAP, consisting of indices obtained from the inferior vena cava, systemic and hepatic veins, tissue Doppler parameters, and right atrial dimensions (2). Because the noninvasive evaluation of RAP involves indirect measurements, multiple factors must be taken into account to provide the most accurate estimate of RAP (2).

Measurement of right atrial pressure or its surrogate central venous pressure via a catheter inserted into the central vein (such as the jugular vein, subclavian, or femoral vein) may be a useful complement to clinical examination in such cases. However, central line insertion requires a certain level of expertise. It may be associated with significant complications depending on both the catheter insertion procedure (such as hemothorax, pneumothorax) and the presence of an indwelling venous catheter in the circulation (such as venous thrombosis, cardiac arrhythmias, sepsis, air embolization or catheter embolization) (7).

Measuring pressures through peripherally inserted venous cannulae (peripheral venous pressure) might be an alternative to central line insertion.

Recently published studies have shown that peripheral venous pressure strongly correlates with right atrial pressure or its surrogate, central venous pressure in patients with acute HF, HF with preserved left ventricular ejection fraction (8–9), and Fontan circulation (10).

A simple tool such as PVP measurement, which can indicate the absolute value and changes in RAP elicited by treatment without the need for central line insertion, can provide an estimate of intravascular volume, a critical component for optimal patient care and management in patients with pulmonary arterial hypertension.

Study Design

This study is a single-center prospective observational study conducted between October 2021 and September 2023 to evaluate the diagnostic accuracy of PVP measurement versus invasively obtained hemodynamic parameters (such as mean right atrial pressure) in patients with pulmonary arterial hypertension scheduled for right heart catheterization. The clinical indication for RHC included confirming the diagnosis of newly diagnosed PAH patients or evaluating treatment effectiveness in patients hospitalized with PAH, assessing hemodynamics for persistence or worsening. A cohort of 138 consecutive patients who met World Health Organization (WHO) diagnostic criteria for group 1 PAH based on clinical evaluation, PVP measurements, and RHC were prospectively assessed. Comprehensive testing was performed at baseline only. Group 1 patients with PAH represented those with idiopathic PAH, PAH associated with collagen vascular disease, and congenital heart disease-related PAH (Eisenmenger's syndrome, PAH associated with systemic-to-pulmonary shunts, PAH after defect correction).

PAH was described a group of PH patients characterized haemodynamically by the presence of pre-capillary PH, defined by a pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg and a PVR > 3 Wood units (WU) in the absence of other causes of pre-capillary PH such as PH due to lung diseases, CTEPH or other rare diseases.

Prior to study enrollment, peripheral venous access was obtained using a 16-gauge IV in the upper extremity. Blood collection for routine laboratory tests, including brain-type natriuretic peptide (BNP), was obtained via this route. PVP was immediately measured by connecting the pressure line of the transducer (TruWave; Edwards Lifesciences, Irvine, CA, USA) directly to the peripheral IV while the pressure transducer remained zeroed at the phlebostatic axis. The patient’s arm was placed parallel to the patient such that the position of the peripheral IV was at the level of the mid-chest. Continuity of the peripheral IV line with the central venous system was confirmed by demonstrating augmentation of the venous pressure waveform after manual circumferential occlusion of the extremity proximal to the catheter. If the pressure waveform failed to augment appropriately, data were not collected, and the patient was documented for study purposes as a technique failure. Peripheral venous pressure measurements were performed by two dedicated investigators who were blinded to the clinical data. The attending physicians were also blinded to the PVP results.

Right femoral central venous access was obtained, and a 6-French pulmonary artery catheter was advanced into the pulmonary artery using standard technique under fluoroscopic guidance. Before obtaining invasive measurements, baseline clinical and demographic data were recorded. Subsequently, right atrium, right ventricle, pulmonary artery, and pulmonary arterial wedge pressure (PAWP) were measured at end-expiration using standard pressure transducers after being zeroed at the phlebostatic axis. Cardiac output and index were measured using the assumed Fick method.

Statistical Analysis

All statistical tests were 2-sided, and P values < 0.05 were considered significant. Statistical analysis was performed using Stata (version 13, StataCorp LP, College Station, TX).

Continuous variables are expressed as median (interquartile range) and categorical variables as n (%). The primary outcome of the study was the degree of correlation between CVP and PVP measurements. Pearson’s correlation coefficients were calculated to assess this correlation. Peripheral edema status was compared similarly with mean PVP and RAP.

One hundred and thirty-eight pulmonary arterial hypertension patients, 42 (30.4%) men and 96 (69.6%) women, aged between 18 and 80 (mean, 43) were included in this study. One hundred and thirty-eight pulmonary arterial hypertension patients, 42 (30.4%) men and 96 (69.6%) women, aged between 18 and 80 (mean, 43) were included in this study. Of these, 44 (31.9%) were idiopathic PAH, 16 (11.6%) were connective tissue-related PAH, and 75 (54.3%) were congenital heart disease-related PAH (Table 1). Of the congenital heart disease-related PAH patients, 42(56%) patients had Eisenmenger's syndrome, 10(13.3) patients had PAH associated with systemic-to-pulmonary shunts, and 23(30.7) patients had PAH after defect correction (Table 1).

Table 1

Demographic, clinical, and laboratory data of all patients in this study
Age, years		43.0 ± 17.8
Sex, female, n(%)		96 (69.6%)
Heart rate, bpm		87.0 ± 15.4
Six-minute walk distance, meter		280.0 (IQR 40–600)
NYHA class	I, n(%) II, n(%) III, n(%) IV, n(%)	6 (4.3) 16(11.6) 80(58) 36 (26.1)
Peripheral edema	0, n(%) 1+, n(%) 2+, n(%) 3+, n(%) 4+, n(%)	30 (21.7) 46(33.3) 39(28.3) 21 (15.2) 2 (1.4)
PAH clinical classification	Idiopathic PAH Connective tissue-related PAH Congenital heart disease-related PAH. Eisenmenger's syndrome PAH associated with systemic-to-pulmonary shunts PAH after defect correction.	44 (31.9%) 16 (11.6%) 75 (54.3%) 42(56%) 10(13.3) 23(30.7)
Medications	Endothelin receptor antagonists, n(%) Phosphodiesterase 5 inhibitors, n(%) Prostacyclin receptor agonist, n(%) Soluble guanylate cyclase stimulator, n(%) Prostacyclin analogs, n(%) Diuretics, n(%) Treatment-naive, n(%)	70(51) 68(49) 8(6) 12(9) 9(7) 69(50) 58(42)
Laboratory data	Pro-brain natriuretic peptide, pg/L High-sensitive troponin, pg/L	399.8 (IQR 10-6287) 100 (IQR 1-949)

Table 2

Hemodynamic parameters of all patients in this study
Pulmonary arterial wedge pressure, mmHg	11.8 ± 4.1
Systolic pulmonary artery pressure, mmHg	85.7 ± 31.0
Diastolic pulmonary artery pressure, mmHg	33.7 ± 17.1
Mean pulmonary artery pressure, mmHg	53.5 ± 21.6
Pulmonary vascular resistance, woods	8.97 ± 6.54
Systolic systemic blood pressure, mmHg	130.5 ± 25.9
Diastolic systemic blood pressure, mmHg	71.5 ± 15.8
Mix venous oxygen saturation, %	83.7 ± 10.1

A significant correlation was detected between peripheral edema and mean right atrial pressure (r = 522; p < 0.001). A significant correlation was also detected between peripheral edema and mean peripheral venous pressure (r = 58; p < 0.001) (Fig. 1).

ROC curve analysis found that a mean PVP lower than 6.5 mmHg was associated with peripheral edema < 1 + in patients with PAH, with a sensitivity of 60% and a specificity of 89% (Area under the ROC curve = 0.75 [95% CI 0.64–0.87]; p < 0.001) (Fig. 2a). In addition, ROC curve analysis found that a mean RAP lower than 5.5 mmHg was associated with Peripheral edema < 1 + in patients with PAH, with a sensitivity of 60% and a specificity of 82% (Area under the ROC curve = 0.78 [95% CI 0.68–0.87]; p < 0.001) (Fig. 2a). ROC curve analysis found that a mean PVP greater than 9.5 mmHg was associated with peripheral edema ≥ 2 + in patients with PAH, with a sensitivity of 90% and a specificity of 61% (Area under the ROC curve = 0.78 [95% CI 0.71–0.86]; p < 0.001) (Fig. 2b). In addition, ROC curve analysis found that a mean RAP greater than 8.5 mmHg was associated with Peripheral edema ≥ 2 + in patients with PAH, with a sensitivity of 66% and a specificity of 71% (Area under the ROC curve = 0.74 [95% CI 0.65–0.82]; p < 0.001) (Fig. 2b). ROC curve analysis found that a mean PVP greater than 10.5 mmHg was associated with peripheral edema ≥ 3 + in patients with PAH, with a sensitivity of 73% and a specificity of 96% (Area under the ROC curve = 0.90 [95% CI 0.84–0.96]; p < 0.001) (Fig. 2c). In addition, ROC curve analysis found that a mean RAP greater than 9.5 mmHg was associated with Peripheral edema ≥ 3 + in patients with PAH, with a sensitivity of 73% and a specificity of 83% (Area under the ROC curve = 0.84 [95% CI 0.76–0.92]; p < 0.001) (Fig. 2c).

A significant correlation was found between mean PVP and RAP (r = 0.839; p < 0.001) (Fig. 3). ROC curve analysis found that a PVP lower than 8.5 mmHg was associated with < 8 mmHg RAP in patients with PAH, with a sensitivity of 72% and a specificity of 94% (Area under the ROC curve = 0.91; 95% CI 0.86–0.96; p < 0.001) (Fig. 4). In addition, a PVP higher than 12.5mmHg was associated with ≥ 12 mmHg RAP in patients with PAH, with a sensitivity of 82% and a specificity of 89% (Area under the ROC curve = 0.92; 95% CI 0.87–0.97; p < 0.001) (Fig. 4).

In this study, it was investigated whether the average PVP measured through a catheter placed in the peripheral vein in patients with PAH was related to the average RAP and whether the change in one was reflected in the change in the other. This study confirms the strong correlation between PVP and invasively obtained RAP in patients with pulmonary arterial hypertension. This study confirms the strong correlation between PVP and invasively obtained RAP in patients with pulmonary arterial hypertension. In our study, there is a significant and strong correlation between average PVP and average RAP. In our study, the average PVP value is slightly higher than the average RAP value. Additionally, a moderately significant correlation was detected between peripheral edema and mean PVP and mean RAP. Moderate results were obtained in ROC curve analyses.

RHC for the measurement of intracardiac pressures has been a mainstay in diagnostic testing for patients with cardiac dysfunction. Nevertheless, in certain cases, an RHC or serial RHCs may not be feasible outside of a catheterization laboratory or an intensive care unit. Furthermore, in many patients, body habitus may limit the accuracy of physical examination estimates of central venous pressure (CVP). Using peripheral venous pressure (PVP) for estimating CVP has been described primarily in the anesthesia (11–13) and critical care studies (14–15); however, few data are available in patients with cardiovascular disease (14, 15). We evaluated the ability of PVP to predict RAP in patients with pulmonary arterial hypertension, whose definitive diagnosis was made by right heart catheterization and which may require serial cardiac catheterization during follow-up.

Prior studies have demonstrated reasonable correlation between CVP and PVP in other patient populations including noncardiac transplant, gastrointestinal surgical, neurosurgical, and pediatric patients (16). Studies in children with cardiac disease are mixed, with poor correlation seen in congenital heart disease but good correlation seen while on cardiopulmonary bypass and in those with Fontan circulation (16). To our knowledge, this is the first study to validate this process in a cohort of adults with PAH. The results add to the generalizability of PVP measurement among a diverse population. In addition, as in most previous studies, larger diameter (16 to 18 gauge) (gray and green, respectively) peripheral IVs were used in our study.

A recently published new study showed that PVP was superior to traditional congestion assessments in predicting RAP increases in patients undergoing pulmonary artery catheterization (17). Furthermore, they confirmed the independent prognostic value of PVP measured at discharge in patients hospitalized with HF (18).

Central venous pressure is one of the clinical parameters used to guide fluid or diuretic administration in patients with pulmonary arterial hypertension. Central line insertion can be associated with significant complications. Some of these complications can be serious. Additionally, central line placement requires expertise and experienced staff. Therefore, Estimation of CVP without insertion of a central venous catheter would be valuable in patients with pulmonary hypertension and in situations where expert assistance for central line insertion is not always immediately available.

This study has significant clinical implications. Practitioners less adept at assessing intracardiac pressures on physical examination may also be aided by PVP measurement. PVP may be particularly useful when jugular venous examination is limited because of body habitus or patient positioning. PVP can be used to evaluate clinical deterioration and volume status in PAH patients. Mean right atrial pressure, which has been shown to have prognostic value and can be used in follow-up, can also be used in situ without the need for right heart catheterization. For this, it needs to be supported by more comprehensive studies.

Restoration of clinical euvolemia is an essential aspect of managing patients with PAH, both in an effort to recover functional status and to improve short- and long-term outcomes. However, due to subclinical hemodynamic congestion as well as the potential difficulty in accurately assessing bedside volume status, many patients with PAH are discharged with elevated right atrial pressures. More accurate assessment of right atrial pressures in the setting of clinical worsening of PAH and at discharge may reduce readmission rates in the first few months after hospitalization. Although right heart catheterization is indicated for invasive hemodynamic assessment to guide management when there is uncertainty regarding volume status, this approach is not feasible in all patients due to the risks involved. For this reason, mean PVP may serve as a valuable clinical surrogate of mean right atrial pressure in patients with PAH and the event of clinical deterioration. Thus, it may eliminate the need for RHC for invasive hemodynamic evaluation in some patients.

The simple measurement of PVP provided accurate information on hemodynamic congestion in the management of patients with pulmonary arterial hypertension. The application of this measurement to clinical practice may improve current assessments of congestion in the management of patients with pulmonary arterial hypertension.

Conflict of interest statement

No conflicts of interest between the authors and/or family members of the scientific and medical committee members or members of the potential conflicts of interest, counseling, expertise, working conditions, shareholding, and similar situations in any firm.

Author Contribution

all authors have made substantial contributions to the conception ,design of the work, the acquisition, analysis, interpretation of data

Statement of ethics

The present study protocol was reviewed and approved by Adana City Training and Research Hospital Ethics Committee. Source of Finance During this study, no financial or spiritual support was received neither from any pharmaceutical company that has a direct connection with the research subject, nor from a company that provides or produces medical instruments and materials which may negatively affect the evaluation process of this study.

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No competing interests reported.

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WITHDRAWN: Peripheral Venous Pressure Measurements to Evaluate Congestion in pulmonary arterial hypertension

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Abstract

Background

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Results

Conclusions

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Introduction

Methods

Statistical Analysis

Results

Discussion

Conclusion

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Conflict of interest statement

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Statement of ethics

References

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