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

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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.

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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

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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.

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Authors and Affiliations

  1. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain

    Ines Garcia-Lunar, Daniel Pereda, Evelyn Santiago, Jorge Nuche, Federico Sierra, Carlos Galán, Valentín Fuster, Borja Ibáñez & Ana García-Álvarez

  2. CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain

    Ines Garcia-Lunar, Daniel Pereda, Carlos Galán, Montserrat Rigol, Borja Ibáñez & Ana García-Álvarez

  3. Hospital Universitario Quirónsalud Madrid, UEM, Madrid, Spain

    Ines Garcia-Lunar

  4. Clinic Cardiovascular Institute, IDIBAPS, Hospital Clínic, Villarroel 170, 08027, Barcelona, Spain

    Daniel Pereda, Evelyn Santiago, Nuria Solanes, María Ascaso, Joaquim Bobí, Ana Paula Dantas, Rodolfo San Antonio, Montserrat Rigol, Manel Sabaté & Ana García-Álvarez

  5. Hospital Universitario Doce de Octubre, Madrid, Spain

    Jorge Nuche

  6. Departamento de Anatomía y Biología Celular, Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain

    Damián Sánchez-Quintana

  7. Philips Healthcare Iberia, Madrid, Spain

    Javier Sánchez-González

  8. CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain

    Joan Albert Barberá

  9. Department of Pulmonary Medicine, Hospital Clínic-IDIBAPS, Barcelona, Spain

    Joan Albert Barberá

  10. Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, USA

    Valentín Fuster

  11. IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain

    Borja Ibáñez

Authors
  1. Ines Garcia-Lunar
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  2. Daniel Pereda
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  3. Evelyn Santiago
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  19. Ana García-Álvarez
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Corresponding author

Correspondence to Ana García-Álvarez.

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

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Garcia-Lunar, I., Pereda, D., Santiago, E. et al. Effect of pulmonary artery denervation in postcapillary pulmonary hypertension: results of a randomized controlled translational study. Basic Res Cardiol 114, 5 (2019). https://doi.org/10.1007/s00395-018-0714-x

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