First in human: the effects of biventricular pacing on cardiac output in severe pulmonary arterial hypertension

  • Ahmet Afşin Oktay
  • Stacy A. Mandras
  • Sangeeta Shah
  • Krishna Kancharla
  • Omar F. Shams
  • Mario I. Pascual
  • Daniel P. MorinEmail author
Original Article


Pulmonary arterial hypertension (PAH) carries high morbidity and mortality despite available treatment options. In severe PAH, right ventricular (RV) diastolic pressure overload leads to interventricular septal bowing, hindering of left ventricular diastolic filling and reduced cardiac output (CO). Some animal studies suggest that pacing may mitigate this effect. We hypothesized that eliminating late diastole via ventricular pacing could improve CO in human subjects with severe PAH. Using minimal to no sedation, we performed transvenous acute biventricular (BiV) pacing and right heart catheterization in six patients with symptomatic PAH. Hemodynamic measurements were taken at baseline and during BiV pacing at various 20-ms intervals of V-V timing. We compared baseline CO to (1) CO while pacing the RV first by 80 ms (mimicking RV-only pacing), and then to (2) CO during pacing at the V-V timing that resulted in the highest CO. All participants were female, PASP 74 ± 14 mmHg, QRS duration 104 ± 20 ms. Compared with baseline, the CO decreased when the RV was paced first by 80 ms (7.2 ± 1.0 vs. 6.2 ± 1.1 L/min, p = 0.028). Pacing with optimal V-V timing produced CO similar to baseline (7.2 ± 1.0 vs. 7.4 ± 1.4, p = 0.92). Two patients (33%) met the predefined endpoint of a 15% increase in CO during pacing at the optimal V-V timing. In symptomatic PAH, V-V optimized acute BiV pacing does not consistently improve CO. However, acute BiV pacing did improve CO in a subset of this cohort. Further research is needed to identify predictors of response to cardiac resynchronization therapy in this population.


Pulmonary hypertension Cardiac resynchronization therapy Cardiac output Pulmonary artery pressure 







Cardiac output


Coronary sinus


Chronic thromboembolic pulmonary hypertension


Diastolic interventricular delay


Hight right atrium


Heart failure with preserved ejection fraction


Left ventricle/ventricular


New York Heart Association


Pulmonary arterial hypertension


Pulmonary artery pressure


Pulmonary artery systolic pressure


Pulmonary capillary wedge pressure


Pulmonary vascular resistance


Right atrial pressure


Right Bundle Branch Block


Right Heart Catheterization


Right ventricle/ventricular


Systemic venous oxygen saturation


Oxygen consumption


Compliance with ethical standards

Conflict of interest

This research was funded by a grant from Medtronic (Minneapolis, Minnesota). The sponsor did not have any impact on subject enrollment, analysis of data, or preparation/approval of the manuscript. The authors declare that they have no conflict of interest.


  1. 1.
    Chang W, Weng S, Hsu C, Shih J, Wang J, Wu C, Chen Z (2016) Prognostic factors in patients with pulmonary hypertension—a nationwide cohort study. J Am Heart Assoc 5(9):e003579PubMedPubMedCentralGoogle Scholar
  2. 2.
    Vonk-Noordegraaf A, Haddad F, Chin KM, Forfia PR, Kawut SM, Lumens J, Naeije R, Newman J, Oudiz RJ, Provencher S, Torbicki A, Voelkel NF, Hassoun PM (2013) Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol 62(25 Suppl):D22–D33CrossRefGoogle Scholar
  3. 3.
    Tan HL, Hardziyenka M, Campian ME, Bouma BJ, Linnenbank AC, De Bruin-Bon HACMR, Kloek JJ, Van Der Wal AC, Baan J, De Beaumont EM, Reesink HJ, De Bakker JMT, Bresser P (2009) Right-to-left ventricular diastolic delay in chronic thromboembolic pulmonary hypertension is associated with activation delay and action potential prolongation in right ventricle. Circ Arrhythmia Electrophysiol 2(5):555–561CrossRefGoogle Scholar
  4. 4.
    Hardziyenka M, Surie S, De Groot JR, De Bruin-Bon HACMR, Knops RE, Remmelink M, Yong ZY, Baan J, Bouma BJ, Bresser P, Tan HL (2011) Right ventricular pacing improves haemodynamics in right ventricular failure from pressure overload: An open observational proof-of-principle study in patients with chronic thromboembolic pulmonary hypertension. Europace 13(12):1753–1759CrossRefGoogle Scholar
  5. 5.
    Westerhof BE, Saouti N, van der Laarse WJ, Westerhof N, Vonk Noordegraaf A (2017) Treatment strategies for the right heart in pulmonary hypertension. Cardiovasc Res 113(12):1465–1473CrossRefGoogle Scholar
  6. 6.
    Handoko ML, De Man FS, Allaart CP, Paulus WJ, Westerhof N, Vonk-Noordegraaf A (2010) Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart. Eur Respir Rev 19(115):72–82CrossRefGoogle Scholar
  7. 7.
    Lumens J, Arts T, Broers B, Boomars KA, van Paassen P, Prinzen FW, Delhaas T (2009) Right ventricular free wall pacing improves cardiac pump function in severe pulmonary arterial hypertension: a computer simulation analysis. Am J Physiol Heart Circ Physiol 297(6):H2196–H2205CrossRefGoogle Scholar
  8. 8.
    Gold MR, Brockman R, Peters RW, Olsovsky MR, Shorofsky SR (2000) Acute hemodynamic effects of right ventricular pacing site and pacing mode in patients with congestive heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 85(9):1106–1109CrossRefGoogle Scholar
  9. 9.
    Wilkoff BL, Cook JR, Epstein AE, Greene HL, Hallstrom AP, Hsia H, Kutalek SP, Sharma A, Chamber D, Implantable Defibrillator Trial Investigators VVI (2002) Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator. JAMA 288(24):3115–3123CrossRefGoogle Scholar
  10. 10.
    Kiehl EL, Makki T, Kumar R, Gumber D, Kwon DH, Rickard JW, Kanj M, Wazni OM, Saliba WI, Varma N, Wilkoff BL, Cantillon DJ (2016) Incidence and predictors of right ventricular pacing-induced cardiomyopathy in patients with complete atrioventricular block and preserved left ventricular systolic function. Hear Rhythm 13(12):2272–2278CrossRefGoogle Scholar
  11. 11.
    Rao P, Faddis M (2017) Cardiac resynchronisation therapy: Current indications, management and basic troubleshooting. Heart 103(24):2000–2007PubMedGoogle Scholar
  12. 12.
    Reddy YNV, Carter RE, Obokata M, Redfield MM, Borlaug BA (2018) A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction. Circulation 138(9):861–870CrossRefGoogle Scholar
  13. 13.
    Burkett DA, Slorach C, Patel SS, Redington AN, Ivy DD, Mertens L, Younoszai AK, Friedberg MK (2016) Impact of pulmonary hemodynamics and ventricular interdependence on left ventricular diastolic function in children with pulmonary hypertension. Circ Cardiovasc Imaging 9:e004612CrossRefGoogle Scholar
  14. 14.
    Gan CT-J, Lankhaar J-W, Marcus JT, Westerhof N, Marques KM, Bronzwaer JGF, Boonstra A, Postmus PE, Vonk-Noordegraaf A (2006) Impaired left ventricular filling due to right-to-left ventricular interaction in patients with pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 290(4):H1528–1533CrossRefGoogle Scholar
  15. 15.
    Jaffe LM, Morin DP (2014) Cardiac resynchronization therapy: History, present status, and future directions. Ochsner J 14(4):596–607PubMedPubMedCentralGoogle Scholar
  16. 16.
    Zhu H, Zou T, Zhong Y, Yang C, Ren Y, Wang F (2019) Prevention of non-response to cardiac resynchronization therapy: points to remember. Heart Fail Rev. CrossRefPubMedGoogle Scholar
  17. 17.
    Handoko ML, Lamberts RR, Redout EM, de Man FS, Boer C, Simonides WS, Paulus WJ, Westerhof N, Allaart CP, Vonk-Noordegraaf A (2009) Right ventricular pacing improves right heart function in experimental pulmonary arterial hypertension: a study in the isolated heart. Am J Physiol Heart Circ Physiol 297(5):H1752–1759CrossRefGoogle Scholar
  18. 18.
    Lumens J, Ploux S, Strik M, Gorcsan J, Cochet H, Derval N, Strom M, Ramanathan C, Ritter P, Haïssaguerre M, Jaïs P, Arts T, Delhaas T, Prinzen FW, Bordachar P (2013) Comparative electromechanical and hemodynamic effects of left ventricular and biventricular pacing in dyssynchronous heart failure: electrical resynchronization versus left-right ventricular interaction. J Am Coll Cardiol 62(25):2395–2403CrossRefGoogle Scholar
  19. 19.
    Narang N, Thibodeau JT, Levine BD, Gore MO, Ayers CR, Lange RA, Cigarroa JE, Turer AT, De Lemos JA, McGuire DK (2014) Inaccuracy of estimated resting oxygen uptake in the clinical setting. Circulation 129(2):203–210CrossRefGoogle Scholar

Copyright information

© Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Cardiovascular Diseases, Ochsner Clinical SchoolJohn Ochsner Heart and Vascular Institute, The University of Queensland School of MedicineNew OrleansUSA

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