Hemodynamic impact of pulmonary vasodilators on single ventricle physiology

Castaldi, Biagio; Bordin, Giulia; Padalino, Massimo A.; Cuppini, Elena; Vida, Vladimiro L.; Milanesi, Ornella

doi:10.1111/1755-5922.12314

Cited by 14 publications

(11 citation statements)

References 18 publications

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“…In such conditions, a pharmacological target strategy using pulmonary vasodilators is of interest. Recent studies have evaluated sildenafil in SV patients and suggested it would decrease pulmonary resistance, improve ventricular filling, and increase exercise tolerance, with low toxicity and good clinical tolerance . A recent randomized study of 19 patients, using pressure/volume curves during cardiac catheterization, and two recent echography studies showed an improvement of ventricular function under sildenafil.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, a TPG above 5 mmHg avoids enrolling patients with isolated ventricular or atrio‐ventricular valve dysfunction. Indeed, diastolic ventricular dysfunction seems to be aggravated by pulmonary vasodilators and may explain discrepancies in the results observed in previous studies . We purposely did not use pulmonary vascular resistance to define patients eligible to the SV‐INHIBITION trial, given the known difficulties to accurately measure pulmonary blood flow in SV physiology.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the use of a selective pulmonary vasodilator in SV may be of interest, in order to decrease trans‐pulmonary gradient (TPG), increase pulmonary blood flow and ventricular preload, and, thus, improve cardiac output and exercise tolerance . Recent studies have suggested that sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, would decrease pulmonary resistance, improve ventricular filling, and improve exercise tolerance, with low toxicity and good clinical tolerance . However, the level of clinical evidence for sildenafil in this indication remains limited, with case reports, small and uncontrolled cohorts, retrospective studies, and studies with a short exposure time to treatment (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of phosphodiesterase type 5 inhibitors in univentricular congenital heart disease: the SV‐INHIBITION study design

et al. 2020

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AimsIn univentricular hearts, selective lung vasodilators such as phosphodiesterase type 5 (PDE5) inhibitors would decrease pulmonary resistance and improve exercise tolerance. However, the level of evidence for the use of PDE5 inhibitors in patients with a single ventricle (SV) remains limited. We present the SV-INHIBITION study rationale, design, and methods. Methods and resultsThe SV-INHIBITION trial is a nationwide multicentre, randomized, double blind, placebo-controlled, Phase III study, aiming to evaluate the efficacy of sildenafil on the ventilatory efficiency during exercise, in teenagers and adult patients (>15 years old) with an SV. Patients with a mean pulmonary arterial pressure >15 mmHg and a trans-pulmonary gradient >5 mmHg, measured by cardiac catheterization, will be eligible. The primary outcome is the variation of the VE/VCO 2 slope, measured by a cardiopulmonary exercise test, between baseline and 6 months of treatment. A total of 50 patients are required to observe a decrease of 5 ± 5 points in the VE/VCO 2 slope, with a power of 90% and an alpha risk of 5%. The secondary outcomes are clinical outcomes, oxygen saturation, 6 min walk test, SV function, NT-proBNP, peak VO 2 , stroke volume, mean pulmonary arterial pressure, trans-pulmonary gradient, SF36 quality of life score, safety, and acceptability. Conclusions The SV-INHIBITION study aims to answer the question whether PDE5 inhibitors should be prescribed in patients with an SV. This trial has been built focusing on the three levels of research defined by the World Health Organization: disability (exercise tolerance), deficit (SV function), and handicap (quality of life).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy of phosphodiesterase type 5 inhibitors in univentricular congenital heart disease: the SV‐INHIBITION study design

et al. 2020

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“…This is particularly surprising given the concerns regarding underlying diastolic dysfunction in single ventricle patients. Castaldi et al . reported a significant increase in PAWP following vasodilator therapy in individuals > 5 years post‐Fontan operation with patients having worst outcomes in their cohort (heart transplantation or death) having marked increases in PAWP post‐vasomodulator therapy.…”

Section: Discussionmentioning

confidence: 99%

Haemodynamic profiles in adult Fontan patients: associated haemodynamics and prognosis

Miranda

Borlaug

Hagler

et al. 2019

European J of Heart Fail

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Aims The Fontan operation is associated with significant long‐term morbidity and mortality, posing challenges in management. No haemodynamic classification has been established to aid management and prognostication of patients with Fontan palliation. Our aim was to assess haemodynamic profiles for Fontan patients and evaluate their relationships to prognosis. Methods and results Eighty‐four adult Fontan patients without obstruction or significant valve disease undergoing cardiac catheterization for Fontan‐related co‐morbidities were divided into four different haemodynamic profiles based on normal/high Fontan pressures (FP) (< 15 or ≥ 15 mmHg) and low/normal cardiac index (CI) (< 2.5 or ≥ 2.5 L/min/m2). Fourteen patients had low CI/high FP (17%), 24 low CI/normal FP (29%), 20 normal CI/high FP (24%), and 26 normal CI/normal FP (31%). Demographic and clinical data were similar among groups except for a trend towards a higher prevalence of cirrhosis in the normal CI/high FP (50%) group. Systemic vascular afterload, assessed by systemic vascular resistance and effective arterial elastance, was higher in patients with low CI/high FP and low CI/normal FP as compared to normal CI profiles. Pulmonary vascular resistance indices were higher in patients with low CI/high FP than all other profiles. The normal CI/high FP haemodynamic profile was an independent predictor of mortality (hazard ratio 4.1, 95% confidence interval 1.2–11.5). Heterotaxy and protein‐losing enteropathy were also predictors of mortality on the multivariate model. Conclusion The proposed haemodynamic classification provides prognostic information in adults post‐Fontan with patients in the normal CI/high FP profile having worse survival. Whether this classification can guide management in these patients deserves further investigation.

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“…19 Finally, a study of 6 Glenn and 12 Fontan patients showed improvement in pulmonary compliance and Nakata index of pulmonary artery size after treatment with sildenafil (n=1), bosentan (n=16), or ambrisentan (n=1). 20 As illustrated, much of the literature has focused on the Fontan population because earlier failure of single-ventricle palliation either after neonatal palliation (depending on the anatomy and amount of pulmonary blood flow after birth) or Glenn operation is more commonly related to ventricular dysfunction or other inherent patient risk factors. In addition, early attrition from the single-ventricle pathway related to pulmonary vascular disease may be better treated with heart transplantation as PVR in this group is rarely high enough to preclude transplantation and long-term outcomes in high-risk single-ventricle patients remain poor.…”

Section: Failing Fontan Populationmentioning

confidence: 99%

Pulmonary Vascular Disease in the Single-Ventricle Patient: Is it Really Pulmonary Hypertension and if So, How and When Should We Treat it?

Handler

Feinstein

2019

Advances in Pulmonary Hypertension

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Despite significant improvements in the surgical and postoperative care for patients with single-ventricle physiology culminating in the Fontan circulation, significant late morbidity and mortality remains. In the setting of passive (ie, non-"pump" driven) pulmonary blood flow, pulmonary vascular resistance (PVR) plays a key role in determining cardiac output, and even slight elevations in PVR may result in significant morbidity. There is now great interest to treat Fontan patients with pulmonary vasodilators in an attempt to "optimize" PVR (and by extension, quality of life) and/ or improve an elevated PVR. This review discusses the hemodynamic implications of the Fontan circulation, the evidence for use of pulmonary vasodilator therapy, and possible target physiologic mechanisms.

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Hemodynamic impact of pulmonary vasodilators on single ventricle physiology

Cited by 14 publications

References 18 publications

Efficacy of phosphodiesterase type 5 inhibitors in univentricular congenital heart disease: the SV‐INHIBITION study design

Efficacy of phosphodiesterase type 5 inhibitors in univentricular congenital heart disease: the SV‐INHIBITION study design

Haemodynamic profiles in adult Fontan patients: associated haemodynamics and prognosis

Pulmonary Vascular Disease in the Single-Ventricle Patient: Is it Really Pulmonary Hypertension and if So, How and When Should We Treat it?

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