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Effect of pulmonary artery denervation in postcapillary pulmonary hypertension: results of a randomized controlled translational study

  • Ines Garcia-Lunar
  • Daniel Pereda
  • Evelyn Santiago
  • Nuria Solanes
  • Jorge Nuche
  • María Ascaso
  • Joaquim Bobí
  • Federico Sierra
  • Ana Paula Dantas
  • Carlos Galán
  • Rodolfo San Antonio
  • Damián Sánchez-Quintana
  • Javier Sánchez-González
  • Joan Albert Barberá
  • Montserrat Rigol
  • Valentín Fuster
  • Borja Ibáñez
  • Manel Sabaté
  • Ana García-ÁlvarezEmail author
Original Contribution

Abstract

There is scarce evidence for pulmonary artery denervation (PADN) as a potential treatment for chronic postcapillary pulmonary hypertension (PH). We aimed to perform a proof-of-concept of PADN in a translational model of chronic PH. Nineteen pigs with chronic postcapillary PH (secondary to pulmonary vein banding) were randomized to surgical-PADN (using bipolar radiofrequency clamps) or sham procedure. Additionally, 6 healthy animals underwent percutaneous-PADN to compare the pulmonary artery (PA) lesion generated with both approaches. In the surgical-PADN arm, hemodynamic evaluation and cardiac magnetic resonance (CMR) were performed at baseline and at 2 and 3-month follow-up. Histological assessment was carried out at the completion of the protocol. Eighteen pigs (6 following surgical-PADN, 6 sham and 6 percutaneous-PADN) completed the protocol. A complete transmural PA lesion was demonstrated using surgical clamps, whereas only focal damage to adventitial fibers was observed after percutaneous-PADN. In the surgical-PADN arm, the hemodynamic profile did not significantly differ between groups neither at baseline [mean pulmonary artery pressure (mPAP) median values of 32.0 vs. 27.5 mmHg, P = 0.394 and indexed pulmonary vascular resistance (iPVR) 5.9 vs. 4.7 WU m2, P = 0.394 for PADN/sham groups, respectively] nor at any follow-up (mPAP of 35.0 vs. 35.0 mmHg, P = 0.236 and iPVR of 8.3 vs. 6.7 WU m2, P = 0.477 at third month in PADN/sham groups, respectively). Surgical-PADN was not associated with any benefit in RV anatomy or function on CMR/histology. In a large-animal model of chronic postcapillary PH, transmural PADN with surgical clamps was associated with a neutral pulmonary hemodynamic effect.

Keywords

Pulmonary hypertension Magnetic resonance imaging Denervation Treatment 

Abbreviations

PH

Pulmonary hypertension

PVR

Pulmonary vascular resistance

RV

Right ventricular

PA

Pulmonary artery

PADN

Pulmonary artery denervation

RHC

Right heart catheterization

CMR

Cardiac magnetic resonance

NA

Noradrenaline

PV

Pulmonary vein

CT

Computed tomography

PAP

Pulmonary arterial pressure

CO

Cardiac output

LVEDP

Left ventricular end-diastolic pressure

LV

Left ventricle

Notes

Acknowledgments

The authors thank Gonzalo J. López for the high-quality cardiac magnetic resonance examinations. Tamara Córdoba, Oscar Sanz, Nuria Valladares, Eugenio Fernández and the rest of the staff working in the animal facilities and CNIC ́s farm were outstanding in animal care and unconditional collaboration. Laura García, Alberto Barroso and Xavier Navarro provided us with the ablation clamps and catheters and assisted us during the denervation procedures. Paula Garcia-Lunar provided valuable support with tissue sampling when it was most needed.

Funding

This work has been partially funded by the grant “Translational research project from the Sociedad Española de Cardiología” (to Dr. García-Álvarez) and by an unrestricted grant from Medtronic. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). IDIBAPS belongs to the CERCA Programme and receives partial funding from the Generalitat de Catalunya.

Compliance with ethical standards

Conflict of interest

This work has been partially funded by an unrestricted grant from Medtronic.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ines Garcia-Lunar
    • 1
    • 2
    • 3
  • Daniel Pereda
    • 1
    • 2
    • 4
  • Evelyn Santiago
    • 1
    • 4
  • Nuria Solanes
    • 4
  • Jorge Nuche
    • 1
    • 5
  • María Ascaso
    • 4
  • Joaquim Bobí
    • 4
  • Federico Sierra
    • 1
  • Ana Paula Dantas
    • 4
  • Carlos Galán
    • 1
    • 2
  • Rodolfo San Antonio
    • 4
  • Damián Sánchez-Quintana
    • 6
  • Javier Sánchez-González
    • 7
  • Joan Albert Barberá
    • 4
  • Montserrat Rigol
    • 4
  • Valentín Fuster
    • 1
    • 8
  • Borja Ibáñez
    • 1
    • 2
    • 9
  • Manel Sabaté
    • 4
  • Ana García-Álvarez
    • 1
    • 4
    Email author
  1. 1.Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)MadridSpain
  2. 2.CIBER de Enfermedades Cardiovasculares (CIBERCV)MadridSpain
  3. 3.Hospital Universitario Quirónsalud Madrid, UEMMadridSpain
  4. 4.Cardiology DepartmentClinic Cardiovascular Institute, IDIBAPS, Hospital ClínicBarcelonaSpain
  5. 5.Hospital Universitario Doce de OctubreMadridSpain
  6. 6.Departamento de Anatomía y Biología Celular, Facultad de Medicina, Universidad de ExtremaduraBadajozSpain
  7. 7.Philips Healthcare IberiaMadridSpain
  8. 8.Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount SinaiNew YorkUSA
  9. 9.IIS-Fundación Jiménez Díaz University HospitalMadridSpain

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