Safety and efficacy of nebulized nitroglycerin as a vaso-reactive agent in pulmonary arterial hypertension

Abstract

Background
Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by elevation in both mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR), ending by right ventricular hypertrophy then failure. Acute vaso-reactivity testing (AVT) is a critical component of right heart catheterization (RHC), its utility to clarify whom patients with PAH could get benefits from high doses calcium channel blockers (CCBs) treatment. While standard agents like intravenous adenosine are effective, they are associated with significant costs and logistical challenges. Nebulized nitroglycerin (NTG) is a readily available, inexpensive vasodilator with a well-established safety profile. This research work aimed to assess the efficacy and safety of nebulized NTG for AVT in patients with PAH, comparing its hemodynamic effects to those of intravenous adenosine.


Methods
This was a prospective, non-randomized, open-label observational crossover study conducted on 20 patients with a confirmed diagnosis of PAH between May 2022 and May 2024. All patients underwent a comprehensive RHC with baseline hemodynamic measurements. Subsequently, AVT was performed using both intravenous adenosine and nebulized nitroglycerin in a crossover design with a sufficient washout period. Pulmonary pressures measurements , including mean, systolic, diastolic pulmonary artery pressures and pulmonary vascular resistance, were meticulously reported before and after the administration of each agent. Adverse events, including changes in heart rate (HR) and systemic blood pressure (BP), were also closely monitored.


Results

Both adenosine and nitroglycerin significantly reduced pulmonary pressures and resistance compared to baseline. The mean mPAP decreased from 52.10 ± 15.59 mmHg at baseline to 45.45 ± 15.21 mmHg with adenosine (
p
< 0.001) and to 41.15 ± 15.55 mmHg with nitroglycerin (
p
< 0.001). The reduction in mPAP was significantly greater with nitroglycerin (
p
< 0.05). Similarly, PVR was reduced from a baseline of 10.14 ± 5.08 Wood units to 8.28 ± 4.19 Wood units with adenosine (
p
< 0.001) and to 6.33 ± 3.44 Wood units with nitroglycerin (
p
< 0.001), with nitroglycerin demonstrating a more pronounced effect (
p
< 0.05). Both agents caused a rise in heart rate and a drop in systemic BP, but no major adverse systemic effects were observed. 7 cases were non responders(35%), 5 cases had classic response to AVT. 4 of them were to nitroglycerin (20%) and 1 was to both drugs (5%). 8 patients had non classic response to AVT, 7 to nitroglycerin (35%) and only 1 to both drugs (5%).



Conclusion
Nebulized nitroglycerin demonstrated favorable acute hemodynamic effects and an acceptable safety profile during vasoreactivity testing. These findings suggest that it may represent a promising alternative vasodilator; however, randomized controlled studies are required to confirm its clinical efficacy and clinical applicability.