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Pulmonary vasodilator-induced haemodynamic decline and recovery post-discontinuation in two single-ventricle cases

Published online by Cambridge University Press:  10 March 2025

Yuichi Ishikawa Open the ORCID record for Yuichi Ishikawa [Opens in a new window] ,
Yuki Iwaya  and
Ayako Kuraoka
Yuichi Ishikawa*
Affiliation:
Department of Pediatric Cardiology, Fukuoka Children’s Hospital, Fukuoka, Japan
Yuki Iwaya
Affiliation:
Department of Pediatric Cardiology, Fukuoka Children’s Hospital, Fukuoka, Japan
Ayako Kuraoka
Affiliation:
Department of Pediatric Cardiology, Fukuoka Children’s Hospital, Fukuoka, Japan
*
Corresponding author: Yuichi Ishikawa; Email: cardiologyfch634@gmail.com
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Abstract

Pulmonary vasodilators increased the systemic-to-pulmonary collateral flow in two single-ventricle cases, causing haemodynamic decline. Discontinuation reversed the collateral flow and improved heart failure, highlighting the need for careful monitoring. Serial cardiac MRI, as a non-invasive tool, may be essential to detect changes in collateral flow and guide vasodilator use for optimal management in this population.

Keywords

pulmonary vasodilatorsingle ventriclesystemic-to-pulmonary collateral flowcardiac MRItwo-dimensional phase contrastFontan

Information

Type
Brief Report
Information
Cardiology in the Young , Volume 35 , Issue 3 , March 2025 , pp. 649 - 651
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Copyright
© The Author(s), 2025. Published by Cambridge University Press

Introduction

Pulmonary vasodilators have been reported to have favourable effects in single-ventricle patients, primarily by reducing pulmonary vascular resistance and mean pulmonary artery pressure across all stages of Fontan physiology. Reference Park1–Reference Jeremiasen, Tran-Lundmark, Idris, Tran and Moledina3 Despite these expected benefits, we encountered two cases of pulmonary vasodilator administration that resulted in increased pulmonary artery pressure, worsening congestive heart failure, and overall haemodynamic decline. In both cases, discontinuing pulmonary vasodilators lowered pulmonary artery pressure and improved heart failure. Serial cardiac MRI using a multi-site 2D phase-contrast method for accurate quantification of systemic-to-pulmonary collateral flow Reference Ishikawa, Urabe and Yamada4–Reference Grosse-Wortmann, Al-Otay and Yoo6 suggested that increased systemic-to-pulmonary collateral flow induced by pulmonary vasodilators was likely the cause of haemodynamic decline.

Case 1

During routine outpatient follow-up, a 45-month-old boy with hypoplastic left heart syndrome presented with elevated plasma B-type natriuretic peptide levels and progressive tricuspid regurgitation. He underwent the Norwood procedure at 4 months of age, followed by a bidirectional cavo-pulmonary shunt at 25 months. Due to concerns about insufficient pulmonary vasculature to achieve Fontan completion, tadalafil was initiated at 12 months, followed by macitentan at 37 months. Despite diuretics dosages, B-type natriuretic peptide rose to 138.7 pg/mL, and tricuspid regurgitation worsened to a moderate level, prompting cardiac catheterisation at 45 months to assess Fontan eligibility. The mean pulmonary artery pressure was 14 mmHg, wedge pressure 10 mmHg, and pulmonary vascular resistance 3.4 Wood units, deeming Fontan completion unsuitable. Serial cardiac MRI revealed a significant increase in systemic-to-pulmonary collateral flow from 1.0 L/min/m2 at 37 months to 3.1 L/min/m2, along with an enlargement of right ventricular end-diastolic volume to 127 ml/m2, implicating pulmonary vasodilators in the haemodynamic decline. After discontinuation, mean pulmonary artery pressure decreased to 10 mmHg, collateral flow reduced to 1.2 L/min/m2, and right ventricular end-diastolic volume returned to 98 ml/m2 at 49 months. B-type natriuretic peptide level decreased to 36.1 pg/mL (Fig. 1), allowing a successful Fontan procedure.

Figure 1.

Progression of haemodynamic and imaging parameters in Case 1 following pulmonary vasodilator use and discontinuation: changes in catheterisation data, CMR flow volumes, and plasma BNP levels in Case 1 are shown. Pulmonary vasodilator administration (tadalafil and macitentan) led to increased systemic-to-pulmonary collateral flow and elevated BNP levels. Discontinuation was followed by reduced pulmonary artery pressure and improved haemodynamics, as illustrated in subsequent CMR and catheterisation data. BNP = (B-type natriuretic peptide); CMR = (Cardiac Magnetic Resonance imaging); PAP = (pulmonary arterial pressure); PAWP = (pulmonary arterial wedge pressure); BCPS = (bidirectional cavo-pulmonary shunt); Ao = (Aorta); Qs = (systemic blood flow); Qp = (pulmonary blood flow); SPCF = (systemic-to-pulmonary collateral flow); SVC = (superior vena cava); IVC = (inferior vena cava); RPV = (right pulmonary vein); LPV = (left pulmonary vein).

Case 2

A 38-month-old girl with hypoplastic left heart syndrome was admitted due to worsening heart failure. At 33 months, she underwent Fontan completion and tricuspid valve plasty; however, because of worsening tricuspid stenosis accompanied by regurgitation, tricuspid valve replacement was performed at 35 months. To reduce pulmonary vascular resistance and support Fontan adaptation, sildenafil was initiated at 33 months and then switched to tadalafil with the addition of macitentan at 38 months during admission. With no improvement under standard heart failure management, cardiac catheterisation and cardiac MRI at 42 months showed an elevated mean pulmonary artery pressure of 18 mmHg, wedge pressure of 13 mmHg, marked right ventricular end-diastolic volume enlargement to 235 ml/m2, a reduced ejection fraction of 27%, and a plasma B-type natriuretic peptide level of 1005 pg/mL. Systemic-to-pulmonary collateral flow increased markedly, from 0.6 L/min/m2 at 33 months to 2.4 L/min/m2. Suspecting pulmonary vasodilators to be the cause, both medications were discontinued. At 47 months, systemic-to-pulmonary collateral flow reduced to 0.8 L/min/m2, mean pulmonary artery pressure decreased to 11 mmHg, wedge pressure decreased to 6 mmHg, and right ventricular end-diastolic volume returned to 206 ml/m2 (Fig. 2). At 63 months, cardiac MRI showed a further reduction in systemic-to-pulmonary collateral flow to 0.1 L/min/m2.

Figure 2.

Progression of haemodynamic and imaging parameters in Case 2 with pulmonary vasodilator adjustments: haemodynamic data, CMR flow volumes, SpO, and BNP levels in Case 2 are displayed. Pulmonary vasodilators (sildenafil, macitentan, tadalafil) were adjusted over time. Increased systemic-to-pulmonary collateral flow and plasma BNP level were observed, with significant improvement in pulmonary parameters following vasodilator discontinuation, as shown in CMR and catheterisation data. BNP = (B-type natriuretic peptide); CMR = (cardiac MRI); Ao = (Aorta); Qs = (systemic blood flow); Qp = (pulmonary blood flow); SPCF = (systemic-to-pulmonary collateral flow); SVC = (superior vena cava); IVC = (inferior vena cava); RPV = (right pulmonary vein); LPV = (left pulmonary vein); TCPC = (total cavo-pulmonary connection); PAP = (pulmonary arterial pressure); PAWP = (pulmonary arterial wedge pressure); RVEDP = (right ventricular end-diastolic pressure).

Discussion

Here, we describe two patients with single-ventricle physiology in whom pulmonary vasodilator use increased the systemic-to-pulmonary collateral flow, leading to elevated pulmonary artery pressure and ventricular volume overload. These cases contrast with previous reports suggesting that pulmonary vasodilators lower pulmonary arterial pressure and benefit single-ventricle physiology.

While some retrospective analyses have suggested that pulmonary vasodilators lower pulmonary arterial pressure and yield favourable effects across all stages of single-ventricle physiology, Reference Park1–Reference Jeremiasen, Tran-Lundmark, Idris, Tran and Moledina3 a meta-analysis of Fontan circulation found no clear benefit. Reference Li, Zhou, An and Feng7 Additionally, a randomised controlled trial of the phosphodiesterase type 5 inhibitor udenafil in post-Fontan patients demonstrated only minimal improvements over placebo: a slight increase in VO2 at anaerobic threshold (+33 vs. −8 ml/min), a small reduction in resting diastolic blood pressure (−2.9 vs. +0.2 mmHg), and a modest rise in oxygen saturation (+0.5 vs. −0.3%). Reference Goldberg, Zak and Goldstein8 This discrepancy may reflect a mix of cases, such as ours, in which increased systemic-to-pulmonary collateral flow leads to haemodynamic decline, and cases with demonstrated benefits. Our findings highlight the need for caution when using pulmonary vasodilators in single-ventricle patients, as increased systemic-to-pulmonary collateral flow and haemodynamic deterioration may coexist with the beneficial effects. Thus, differentiating these cases is essential. Serial cardiac MRI with multi-site 2D phase-contrast methods Reference Ishikawa, Urabe and Yamada4 may be indispensable, and longitudinal MRI assessments could clarify the impact of pulmonary vasodilators on single-ventricle physiology and establish their efficacy.

Importantly, we observed that the systemic-to-pulmonary collateral flow changes induced by pulmonary vasodilators were reversible. Pulmonary vasodilators likely dilate collateral vessels, similar to pulmonary vessels, temporarily reducing resistance and increasing flow without inducing neovascularization, as the systemic-to-pulmonary collateral flow returns to baseline upon discontinuation. Changes were evident within six months, suggesting that both the onset and offset of effects probably occurred within one or two months.

Similar cases are likely to occur among patients previously diagnosed with idiopathic cardiac enlargement and heart failure. This underscores the need for paediatric cardiologists to reconsider the significance of systemic-to-pulmonary collateral flow in single-ventricle physiology. The post-Fontan worsening of tricuspid stenosis and regurgitation in Case 2 may also have been caused by the increased systemic-to-pulmonary collateral flow induced by pulmonary vasodilators. Had this perspective been considered earlier, earlier discontinuation of pulmonary vasodilators might have prevented the need for tricuspid valve replacement. Cardiac MRI, as the only non-invasive modality capable of quantifying systemic-to-pulmonary collateral flow, should be more widely utilised and performed at more frequent intervals to ensure accurate diagnosis and appropriate management of these patients.

Conclusion

Pulmonary vasodilators may increase systemic-to-pulmonary collateral flow in single-ventricle patients, highlighting the need for routine and frequent cardiac MRI monitoring to detect this complication. Further research should examine the extent, reversibility, and long-term clinical impact of these changes to optimise the management of this population.

Financial support

This research received no specific grants from any funding agency, commercial sector, or not-for-profit sector.

Competing interests

None.

Ethical standards

Written informed consent was obtained from the patient’s parents for the publication of this case report.

References

Park, I-S. Efficacy of pulmonary vasodilator therapy in patients with functionally single ventricle. Int Heart J 2015; 56: S26–S30.10.1536/ihj.14-392CrossRefGoogle ScholarPubMed
Mori, H, Park, I-S, Yamagishi, H et al. Sildenafil reduces pulmonary vascular resistance in single ventricular physiology. Int J Cardiol 2016; 221: 122–127.10.1016/j.ijcard.2016.06.322CrossRefGoogle ScholarPubMed
Jeremiasen, I, Tran-Lundmark, K, Idris, N, Tran, P-K, Moledina, S. Pulmonary vasodilator therapy in children with single ventricle physiology: effects on saturation and pulmonary arterial pressure. Pediatr Cardiol 2020; 41: 1651–1659.10.1007/s00246-020-02424-wCrossRefGoogle ScholarPubMed
Ishikawa, Y, Urabe, H, Yamada, Y et al. Normal ventricular and regional blood flow volumes and native T1 values in healthy Japanese children obtained from comprehensive cardiovascular magnetic resonance imaging. Int Heart J 2023; 64: 663–671.10.1536/ihj.23-022CrossRefGoogle ScholarPubMed
Whitehead, KK, Gillespie, MJ, Harris, MA, Fogel, MA, Rome, JJ. Noninvasive quantification of systemic-to-pulmonary collateral flow: a major source of inefficiency in patients with superior cavopulmonary connections. Circ Cardiovasc Imaging 2009; 2: 405–411.10.1161/CIRCIMAGING.108.832113CrossRefGoogle Scholar
Grosse-Wortmann, L, Al-Otay, A, Yoo, S-J. Aortopulmonary collaterals after bidirectional cavopulmonary connection or Fontan completion: quantification with MRI. Circ Cardiovasc Imaging 2009; 2: 219–225.10.1161/CIRCIMAGING.108.834192CrossRefGoogle ScholarPubMed
Li, D, Zhou, X, An, Q, Feng, Y. Pulmonary vasodilator therapy after the Fontan procedure: a meta-analysis. Heart Fail Rev 2021; 26: 91–100.10.1007/s10741-019-09905-yCrossRefGoogle ScholarPubMed
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Figure 0

Figure 1. Progression of haemodynamic and imaging parameters in Case 1 following pulmonary vasodilator use and discontinuation: changes in catheterisation data, CMR flow volumes, and plasma BNP levels in Case 1 are shown. Pulmonary vasodilator administration (tadalafil and macitentan) led to increased systemic-to-pulmonary collateral flow and elevated BNP levels. Discontinuation was followed by reduced pulmonary artery pressure and improved haemodynamics, as illustrated in subsequent CMR and catheterisation data. BNP = (B-type natriuretic peptide); CMR = (Cardiac Magnetic Resonance imaging); PAP = (pulmonary arterial pressure); PAWP = (pulmonary arterial wedge pressure); BCPS = (bidirectional cavo-pulmonary shunt); Ao = (Aorta); Qs = (systemic blood flow); Qp = (pulmonary blood flow); SPCF = (systemic-to-pulmonary collateral flow); SVC = (superior vena cava); IVC = (inferior vena cava); RPV = (right pulmonary vein); LPV = (left pulmonary vein).

Figure 1

Figure 2. Progression of haemodynamic and imaging parameters in Case 2 with pulmonary vasodilator adjustments: haemodynamic data, CMR flow volumes, SpO, and BNP levels in Case 2 are displayed. Pulmonary vasodilators (sildenafil, macitentan, tadalafil) were adjusted over time. Increased systemic-to-pulmonary collateral flow and plasma BNP level were observed, with significant improvement in pulmonary parameters following vasodilator discontinuation, as shown in CMR and catheterisation data. BNP = (B-type natriuretic peptide); CMR = (cardiac MRI); Ao = (Aorta); Qs = (systemic blood flow); Qp = (pulmonary blood flow); SPCF = (systemic-to-pulmonary collateral flow); SVC = (superior vena cava); IVC = (inferior vena cava); RPV = (right pulmonary vein); LPV = (left pulmonary vein); TCPC = (total cavo-pulmonary connection); PAP = (pulmonary arterial pressure); PAWP = (pulmonary arterial wedge pressure); RVEDP = (right ventricular end-diastolic pressure).