Evaluating right ventricle and pulmonary pressure changes after foam sclerotherapy injection for great saphenous vein incompetence

Abstract

Background

Ultrasound-guided foam sclerotherapy (UGFS) is a minimally invasive procedure recommended for the management of chronic venous disease, particularly for varicose veins and saphenous trunk insufficiency, although rare, systemic effects may occur. The study aims to evaluate the impact of UGFS on pulmonary artery pressure and right ventricular function through indirect echocardiographic measurements.

Material and Methods

A total of 50 patients with incompetent great saphenous veins underwent UGFS. Preoperative assessments and echocardiographic monitoring of right heart function were conducted at baseline (T0), 5 min (T5), 10 min (T10), and 15 min (T15) after FS injection. Primary endpoint included changes in systolic pulmonary artery pressure (PAPs), while secondary endpoints focused on tricuspid annular plane systolic excursion (TAPSE) and right ventricular diameter (RVD1). Statistical analyses were performed using paired t-tests and linear mixed models.

Results

The results indicated a significant increase in PAPs from T0 to T10 (mean increase of 8.13 mmHg, p < .01) and T5, with a reduction at T15 that remained above baseline (mean difference of 3.01 mmHg, p < .01). TAPSE showed a significant increase at T15 compared to T0 (mean increase of 1.6 mm, p = .04). No significant changes were observed in RVD1. Importantly, no local or systemic complications occurred, and all patients remained asymptomatic.

Conclusion

UGFS is a safe and effective treatment for chronic venous disease, with transient and benign alterations in right heart hemodynamic likely attributable to foam degradation products. Further studies with larger cohorts and longer follow-up are warranted to enhance understanding of the long-term effects of UGFS on pulmonary hemodynamic and right ventricular function.

Keywords

ultrasound guided foam sclerotherapy chronic venous disease varicose veins pulmonary hypertension

Introduction

Ultrasound-guided foam sclerotherapy (UGFS) is a minimally invasive, image-guided procedure used in the management of chronic venous disease and largely recommended due to its safe and effective profile in varicose veins and saphenous trunks insufficiency management.¹ The systemic effects of sclerotherapy are rare but clinically significant and include a range of potential adverse events. The most important systemic complications are neurological events (such as transient ischemic attack, ischemic stroke, migraine, and visual disturbances), cardiac toxicity (including myocardial infarction and Takotsubo cardiomyopathy), pulmonary embolism, deep vein thrombosis, anaphylaxis, and septicaemia. These events are infrequent, with severe complications (death, anaphylaxis, pulmonary emboli, stroke, large areas of skin necrosis) occurring in less than 0.01% of cases, as reported by the Society for Vascular Surgery and the American Venous Forum. Neurological complications are more likely in patients with a right-to-left cardiac shunt, such as a patent foramen ovale, and caution is advised in these patients.^1–3

There have been rare reports of deep vein thrombosis and pulmonary embolism, but these are uncommon when standard precautions are followed.⁴ The Society for Vascular Surgery and the American Venous Forum recommend techniques to minimize foam migration, such as leg elevation and avoidance of occlusive pressure at the saphenofemoral junction, to reduce the risk of systemic embolization.^5,6 Despite systemic effect are very rare, some Authors described FS presence in right heart chambers and consequently in pulmonary circulation, with potential pulmonary artery damage and hypertension.^7–9 In this scenario, monitoring right cardiac haemodynamic could be potentially useful for better understanding if sclerotherapy affects cardiac and/or pulmonary performance. Indeed, identifying such changes may optimize the application of sclerotherapy in selected patients through tailored administration techniques and dosages.

The aim of this report is to describe how indirect echocardiographic measurements of pulmonary hypertension and right ventricular (RV) function change during FS injection.

Methods

Non-consecutive patients underwent UGFS of the incompetent great saphenous vein (GSV) and concomitant tributaries treatment were enrolled at a specialized venous centre with more than 2000 accesses per year for chronic venous disorder (Rosi Vascular Center, Perugia, Italy) from January 1 from 31 March 2024. Each patient was followed and operated by a healthcare professional renowned for UGFS treatment. After clinical and color Doppler ultrasound scan evaluation, UGFS was proposed in accordance with sclerotherapy guidelines, in terms of patients’ assessment, foam preparation with Tessari method (polidocanol 1-2% mixed 1:4 with air; Discard type II syringe without silicone) and perioperative work-up, including standing in Fowler’s position (supine position with the head of the bed elevated between 45 and 60°) for 15 min after foam injection.¹⁰ In addition to the inclusion/exclusion criteria recommended by the UGFS guidelines (Table 1), individuals suffering from secondary and idiopathic pulmonary hypertension, with cardiac alterations characterized by a left ventricular ejection fraction of less than 55% - generally considered below the normal range of 55-70%, indicating a potential reduction in the heart’s pumping efficiency -, as well as those with valvular stenosis, dilated RV, chronic renal failure, chronic respiratory failure, and collagenopathies were excluded from the study.

Table 1.

Foam sclerotherapy contraindications, adapted from rabe et al.¹⁰ DVT, deep vein thrombosis; PE, pulmonary embolism; PFO, patent foramen ovale; PAOD, peripheral arterial occlusive disease; SVT, superficial venous thrombosis.

Type	Contraindications
Absolute	Allergy to sclerosant; acute DVT/PE; local or systemic infection; prolonged immobility
Absolute (foam only)	Symptomatic right-to-left shunt (e.g. PFO)
Relative*	Pregnancy; breastfeeding†; severe PAOD; poor general health; allergy predisposition; high thromboembolic risk‡; acute SVT
Relative (foam only)*	Neurological symptoms (e.g. migraine) after prior foam sclerotherapy

*Individual benefit–risk assessment required.

†Interrupt breastfeeding for 2–3 days.

‡Includes prior thromboembolism, severe thrombophilia, hypercoagulable state, or active cancer.

Before, during and after UGFS, a certified and experienced cardiologist ultrasound specialist monitored right heart function and performance. In particular, TAPSE (Tricuspid Annular Plane Systolic Excursion), PAPs (Systolic Pulmonary Artery Pressure) and RVD1 (Right ventricular basal diameter at end-diastole) were calculated at baseline (T0), 5 min after UGFS injection (T5), 10 min after UGFS injection (T10) and 15 min after UGFS injection, using a postoperative 18 mmHg elastic stockings on the operated limb (T15). Potential presence of shunts, assessed via the Valsalva manoeuvre, was evaluated before the procedure. Systolic and diastolic blood pressure were also monitored for the whole follow-up time. All patients sign an informed consent for both intervention and research purpose. The study was carried out according to the declaration of Helsinki.

Primary and secondary endpoints

Primary endpoint was change in PAPs value at T1, T5 and T15 if compared with T0. Secondary outcomes were changes in TAPSE and RVD1 values at T1, T5 and T15 if compared with T0.

Statistical analysis

Clinical data were recorded and tabulated in a Microsoft Excel (Microsoft Corp., Redmond, WA, USA) spreadsheet; statistical analysis was performed with IBM SPSS Statistics for Windows, Version 25 (IBM Corp., Armonk, NY, USA). Missing data were reported during data extraction and flagged as such (-). Categorical/nominal variables were presented using frequencies and percentages, while continuous variables by mean (µ) ± standard deviation (SD), or median with interquartile range (IQR) and ranges, according to data distribution. The t-test for paired data for each variable of interest was used, to verify the null hypothesis of absence of differences between average values observed in adjacent (i.e., T0 vs T1, T1 vs T5, T5 vs T15) or between the first and the last (i.e., T0 vs T15) follow-up measurement. When useful, linear mixed models (LMMs) were used for providing influence of demographic or procedure-related variables on PAPs, TAPSE and RVD1. A two-tailed p-value <.05 was considered significant.

Results

A total of 50 patients were included in the study and into the analysis (52% female, 48% male), with an average age of 57 ± 14 years. All selected patients had GSV incompetence with associated varicose veins (Clinical-Etiological-Anatomical-Pathophysiological classification [CEAP] C2sEpAsPr). UGFS was performed in all patients; foam amount was 10 ± 1 cc. Neither local nor systemic complications occurred. All patients remain asymptomatic.

Table 2 summarizes PAPs, TAPSE and RVD1 values at baseline and for each postoperative interval.

Table 2.

Baseline and post sclerosing foam injection Pulmonary artery pressures (PAPs), Tricuspid annular plane systolic excursion (TAPSE) and Right ventricular diameter at end-diastole (RVD1) measurements.

Variable	Time	µ	SD	Min	Max
PAPs, mmHg	T0	19.72	8.42	10.90	36.00
	T1	27.84	15.88	11.90	72.00
	T5	28.73	14.89	10.00	73.70
	T15	22.73	7.28	13.00	40.20
TAPSE, mm	T0	24.75	2.82	20.00	33.90
	T1	24.39	2.01	20.00	27.90
	T5	25.00	2.60	22.00	33.50
	T15	26.37	4.58	20.40	40.00
RDV1, mm	T0	30.77	9.25	19.00	52.80
	T1	31.49	9.98	19.00	53.70
	T5	31.36	8.88	19.00	51.00
	T15	30.89	8.47	19.00	50.00

Table 3 describes PAPs, TAPSE and RVD1 differences during the follow-up. The analysis revealed significant changes in the variables under study. For the PAPs, an average significant increase of 8.13 from T0 to T1 was observed. Although this increase diminished in subsequent assessments, the value at T15 remained significantly higher than the average observed at T0, with a difference of 3.01. In contrast, the TAPSE showed a noteworthy average increase of 1.652 at T15 compared to T0, which was also statistically significant. However, for the RVD1, no statistically significant average difference was detected across the time points.

Table 3.

Differences in Pulmonary artery pressures (PAPs), Tricuspid annular plane systolic excursion (TAPSE) and Right ventricular diameter at end-diastole (RVD1) measurements before and after sclerosing foam injection.

Variable	H₀	H₁	Diff.	SE	l ₁	l ₂	t value	df	P
PAPs, mmHg	μ_T1 = μ_T0	μ_T1 > μ_T0	8.127	3.014	1.918	14.335	2.696	25	<0.01
	μ_T5 = μ_T1	μ_T5 > μ_T1	0.885	3.145	−5.592	7.361	0.281	25	0.39
	μ_T15 = μ_T5	μ_T15 < μ_T5	−5.996	2.875	−11.918	−0.074	−2.085	25	0.02
	μ_T15 = μ_T0	μ_T15 > μ_T0	3.015	1.350	0.234	5.796	2.233	25	0.01
TAPSE, mm	μ_T1 = μ_T0	μ_T1 < μ_T0	−0.362	0.469	−1.327	0.604	−0.772	25	0.22
	μ_T5 = μ_T1	μ_T5 > μ_T1	0.608	0.455	−0.323	1.545	1.335	25	0.09
	μ_T15 = μ_T5	μ_T15 > μ_T5	1.428	0.724	−0.066	2.922	1.973	24	0.03
	μ_T15 = μ_T0	μ_T15 > μ_T0	1.652	0.896	−0.196	3500	1.845	24	0.04
RDV1, mm	μ_T1 = μ_T0	μ_T1 > μ_T0	0.723	1.010	−1.357	2.803	0.716	25	0.24
	μ_T5 = μ_T1	μ_T5 < μ_T1	−0.135	0.554	−1.275	1.006	−0.243	25	0.40
	μ_T15 = μ_T5	μ_T15 < μ_T5	−0.079	0.534	−1.184	1.026	−0.148	23	0.44
	μ_T15 = μ_T0	μ_T15 > μ_T0	0.346	0.764	−1.234	1.926	0.453	23	0.32

Table 4 summarises multivariate analysis mixing baseline demographic patients’ characteristics. Despite age, as well-know, influences right ventricle performance, PAPs and TAPSE maintain their significance across follow-up intervals.

Table 4.

Multivariate analysis for Pulmonary artery pressures (PAPs), Tricuspid annular plane systolic excursion (TAPSE) and Right ventricular diameter at end-diastole (RVD1) measurements before and after sclerosing foam injection. SBP and DBP: mean systolic and diastolic blood pressure.

Variable	Covariate	Coeff.	St.Err.	l ₁	l ₂	z value	p-value
PAPs, mmHg	T1 vs T0	8.127	2.736	2.764	13.490	2.97	< 0.01
	T5 vs T0	9.012	2.734	3.649	14.374	3.29	< 0.01
	T15 vs T0	3.015	2.736	−2.347	8.378	1.10	0.27
	Sex, male	1.351	3.037	−4.601	7.303	0.44	0.65
	Age	0.289	0.114	0.065	0.512	2.53	0.01
	SBP	−0.061	0.195	−0.443	0.322	−0.31	0.75
	DBP	−0.212	0.255	−0.712	0.288	−0.83	0.40
TAPSE, mm	T1 vs T0	−0.362	0.649	−1.634	0.911	−0.56	0.57
	T5 vs T0	0.246	0.649	−1.026	1.518	0.38	0.70
	T15 vs T0	1.653	0.657	0.365	2.941	2.52	0.01
	Sex, male	−0.033	0.875	−1.748	1.682	−0.04	0.97
	Age	0.065	0.033	0.001	0.130	2.00	0.04
	SBP	−0.030	0.056	−0.140	0.080	−0.54	0.59
	DBP	0.005	0.073	−0.139	0.149	0.06	0.95
RVD1, mm	T1 vs T0	0.723	0.734	−0.716	2.162	0.98	0.32
	T5 vs T0	0.588	0.734	−0.850	2.027	0.80	0.42
	T15 vs T0	0.454	0.754	−1.024	1.932	0.60	0.54
	Sex, male	5.235	3.108	−0.866	11.317	1.68	0.09
	Age	0.278	0.117	0.049	0.506	2.38	0.01
	SBP	−0.100	0.200	−0.492	0.291	−0.50	0.61
	DBP	−0.175	0.261	−0.687	0.337	−0.67	0.50

Discussion

Table 5 summarizes definition, normal value and prognostic role of PAPs, TAPSE and RDV1.

Table 5.

Definitions and clinical relevance of Pulmonary artery pressures (PAPs), Tricuspid annular plane systolic excursion (TAPSE) and Right ventricular diameter at end-diastole (RVD1) values.

Pulmonary artery pressures (PAP), measured in mmHg, are central to the diagnosis and assessment of pulmonary hypertension (PH). Normal systolic PAP (PAPs) by echocardiography is typically <35 mmHg. Elevated PAPs indicate increased right ventricular (RV) afterload and are associated with RV dysfunction and adverse outcomes in PH and right heart failure.

Tricuspid annular plane systolic excursion (TAPSE), measured in mm (or cm), quantifies RV longitudinal systolic function. A normal TAPSE is ≥17 mm (1.7 cm); values below this threshold indicate impaired RV systolic function and are associated with worse prognosis in PH and heart failure. TAPSE is easy to obtain, reproducible, and correlates with RV ejection fraction, but is load-dependent and may not reflect regional dysfunction. The TAPSE/sPAP ratio is increasingly used as a noninvasive marker of RV–pulmonary arterial coupling, with lower values indicating RV–PA uncoupling and poor prognosis.

Right ventricular diameter at end-diastole (RVD1), measured in mm from the apical four-chamber view, reflects RV size. Normal RVD1 is ≤41 mm; values above this suggest RV dilation, which is an early marker of chronic pressure or volume overload and is associated with adverse outcomes in PH and RV failure.

Together, these parameters are essential for the non-invasive evaluation of right heart structure and function, risk stratification, and monitoring of disease progression and therapeutic response in pulmonary hypertension and right heart failure. Indeed, the American Society of Echocardiography recommends them for comprehensive right ventricular assessment.¹¹ The cardiac investigations were deliberately selected to provide a focused, non-invasive, and guideline-supported assessment of right ventricular function and pulmonary hemodynamic, which are the physiological compartments most plausibly affected by transient foam migration into the pulmonary circulation. The timing of echocardiographic assessments was specifically chosen to capture immediate and short-term, reversible hemodynamic responses following foam sclerotherapy, rather than delayed structural or functional cardiac alterations. Fast changes could reflect a short-lived increase in pulmonary vascular tone following foam injection, possibly mediated by microembolization or release of vasoactive substances (e.g. endothelin-1). The study was undertaken to address a specific gap in current knowledge regarding the acute cardiopulmonary effects of UGFS, particularly given sporadic reports of foam passage into the right heart and pulmonary circulation and the absence of systematic hemodynamic monitoring in routine clinical practice.

Given this premise, the study presented here had to use these parameters to demonstrate that the impact of foam sclerosing with POL on the pulmonary circulation and right heart chambers is completely negligible. To our knowledge, this is the first study to evaluate cardiac performance after UGFS using POL and the Tessari method.

Some authors have described alarming cases in the case of ethanol sclerotherapy, particularly used for arteriovenous malformations. Indeed, ethanol sclerotherapy acutely increases PAPs. Mean PAP can exceed 25 mmHg in up to 30% of sessions¹² and the magnitude of PAP rise correlates with both the single and cumulative ethanol dose administered.¹³ The highest PAPs are often seen during the recovery period after the procedure, and these elevations can be clinically significant, requiring close hemodynamic monitoring and, in some protocols, prophylactic nitroglycerin infusion to mitigate pulmonary vasoconstriction.¹⁴

Pulmonary-damaging effects of POL have also been demonstrated in animal studies, although these studies exposed animals to concentrations of the sclerosing agent much higher than those that can be used in humans.^9,15,16 Despite this bias, is crucial to moderate the quantity of foam or liquid for session, in order to minimize potential systemic and organ damage.

In our study, despite a transient increase in PAPs and TAPSE, no symptoms/sings were observed. Moreover, these measurements remained well below the pathological limits, ensuring an additional safety profile.

Why have PAPs and TAPSEs increased? Knowing that the vast majority of the sclerosing agent is bound to the blood proteins and diluted/inactivated¹⁷ the cause of these findings could be explained by another pathogenetic mechanisms, based on endothelial release of vasoactive molecules, such as endothelin-1 (ET-1), histamine or serotonin as FS catabolites.^18,19 Foam sclerotherapy is associated with a significant acute increase in circulating ET-1 levels. This has been demonstrated in both animal and human studies, with ET-1 release occurring within minutes after foam sclerotherapy and correlating with local venous concentrations.^18,20 Furthermore, ET-1 has a complex and sometimes contradictory role in the pulmonary circulation, acting as both a vasoconstrictor and, in some cases, a vasodilator. It can contribute to increased pulmonary vascular resistance, particularly in pulmonary hypertension, due to its potent vasoconstricting and mitogenic (promoting cell growth) properties. However, ET-1 can also cause vasodilation in certain contexts, and its overall effect on vascular tone depends on factors like the dose, the specific receptors involved, and the pre-existing tone of the pulmonary vessels.²¹ Being dose dependent, the effect of ET-1 during UGFS using safety precautions could promote a modest and transient vasoconstrictor effect.

Limitations of the study include its small sample size and the absence of long-term follow-up, which restricts the generalizability of the findings. Additionally, the study’s design does not allow for the assessment of the long-term effects of UGFS on pulmonary hypertension and right ventricular function, leaving a gap for future research to explore these dynamics further.

Conclusion

UGFS appears to be a safe and effective option for treating chronic venous disease, with some transient, reversible and totally benign changes in right circulation haemodynamic, probably due to foam catabolites. Further studies are needed to provide bigger patients cohort and increase the robustness of these results, as well as long-term consequences.

Footnotes

ORCID iD

Daniele Bissacco

Ethical considerations

The local ethics committee approved this study.

Author contributions

*conception and design of the study: GR, CC, DC, DB

*acquisition of data: GR, CC, DC

*analysis and interpretation of data: GR, CC, DC, DB

*drafting the article: GR, DB

*revising it critically: GR, CC, DC, DB

*final approval of the version to be submitted: GR, CC, DC, DB

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Guarantor

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