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Editorial| Volume 35, ISSUE 6, P1565-1567, June 2021

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Protecting the Right Ventricle Network (PRORVNet): Time to Defend the “Forgotten Ventricle”?

Published:January 07, 2021DOI:https://doi.org/10.1053/j.jvca.2021.01.002
      HISTORICALLY, insight into the right ventricle's role in health and disease has lagged behind that of the left ventricle. It is easy to stigmatize the right ventricle as a passive conduit of the heart and, thus, regard it as less important because it only pumps blood into a single organ, the lungs. However, the circulatory system is a complex closed system and requires both ventricles to interdependently work together. The failure of one deleteriously affects the performance of the other.
      • Vonk Noordegraaf A
      • Chin KM
      • Haddad F
      • et al.
      Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: An update.
      Therapeutic management of right ventricular (RV) dysfunction also has lagged behind that of the left ventricle. Current strategies often involve execution of therapies directed at multiple targets to optimize RV preload, contractility, and afterload while maintaining a favorable balance between the right- and left-sided circulations.
      • Vonk Noordegraaf A
      • Chin KM
      • Haddad F
      • et al.
      Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: An update.
      ,
      • Vieillard-Baron A
      • Naeije R
      • Haddad F
      • et al.
      Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.
      RV failure (RVF) occurs when the right ventricle is unable to meet flow demands without excessive use of the Frank-Starling mechanism.
      • Vieillard-Baron A
      • Naeije R
      • Haddad F
      • et al.
      Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.
      Successful adaptation of the right ventricle to different acute pathophysiologic states (eg, altered loading conditions and dynamic contractility [ie, afterload coupling]) is a major determinant of outcomes; however, despite this, acute RVF in any setting significantly increases mortality.
      • Vieillard-Baron A
      • Naeije R
      • Haddad F
      • et al.
      Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.
      • Vonk-Noordegraaf A
      • Haddad F
      • Chin KM
      • et al.
      Right heart adaptation to pulmonary arterial hypertension: Physiology and pathobiology.
      • Meyer P
      • Filippatos GS
      • Ahmed MI
      • et al.
      Effects of right ventricular ejection fraction on outcomes in chronic systolic heart failure.
      • Kucher N
      • Rossi E
      • De Rosa M
      • et al.
      Massive pulmonary embolism.
      • Mekontso-Dessap A
      • Boissier F
      • Charron C
      • et al.
      Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: Prevalence, predictors, and clinical impact.
      • Sztrymf B
      • Souza R
      • Bertoletti L
      • et al.
      Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension.
      • Hamon M
      • Agostini D
      • Le Page O
      • et al.
      Prognostic impact of right ventricular involvement in patients with acute myocardial infarction: Meta-analysis.
      • Vanderpool RR
      • Pinsky MR
      • Naeije R
      • et al.
      RV–pulmonary arterial coupling predicts outcome in patients referred for pulmonary hypertension.
      • Wardi G
      • Blanchard D
      • Dittrich T
      • et al.
      Right ventricle dysfunction and echocardiographic parameters in the post-cardiac arrest patients: A retrospective cohort study.
      RVF is multifactorial (Fig 1) and carries a high mortality.
      • Sztrymf B
      • Souza R
      • Bertoletti L
      • et al.
      Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension.
      In patients with acute respiratory distress syndrome, the reported incidence of RV dysfunction is 25% to 50% and has a negative effect on the course of the syndrome.
      • Price LC
      • McAuley DF
      • Marino PS
      • et al.
      Pathophysiology of pulmonary hypertension in acute lung injury.
      • Zochios V
      • Parhar K
      • Tunnicliffe W
      • et al.
      The right ventricle in ARDS.
      • Barnes T
      • Zochios V
      • Parhar K.
      Re-examining permissive hypercapnia in ARDS: A narrative review.
      It is contributed to by lung inflammation, pulmonary vascular dysfunction, and positive-pressure invasive ventilation.
      • Price LC
      • McAuley DF
      • Marino PS
      • et al.
      Pathophysiology of pulmonary hypertension in acute lung injury.
      Isolated RV dysfunction in patients with sepsis reflects inability of the right ventricle to adapt to physiologic stress and endothelial dysfunction, and it is an independent predictor of long-term mortality.
      • Vallabhajosyula S
      • Kumar M
      • Pandompatam G
      • et al.
      Prognostic impact of isolated right ventricular dysfunction in sepsis and septic shock: An 8-year historical cohort study.
      In RV infarction there are reduced RV contractility and right ventricle-pulmonary arterial uncoupling, leading to RVF.
      • Vieillard-Baron A
      • Naeije R
      • Haddad F
      • et al.
      Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.
      ,
      • Harjola VP
      • Mebazaa A
      • Celutkiene J
      • et al.
      Contemporary management of acute right ventricular failure: A statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology.
      RV dysfunction leading to worse outcomes has been associated with coronary artery surgery with cardiopulmonary bypass, heart transplantation, left ventricular assist device implantation, congenital heart corrective cardiac surgery, and selective lung ventilation in thoracic surgery.
      • Harjola VP
      • Mebazaa A
      • Celutkiene J
      • et al.
      Contemporary management of acute right ventricular failure: A statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology.
      • Zanobini M
      • Saccocci M
      • Tamborini G
      • et al.
      Postoperative echocardiographic reduction of right ventricular function: Is pericardial opening modality the main culprit?.
      • Bianco JC
      • Mc Loughlin S
      • Denault AY
      • et al.
      Heart transplantation in patients >60 years: Importance of relative pulmonary hypertension and right ventricular failure on midterm survival.
      • Soliman OII
      • Akin S
      • Muslem R
      • et al.
      Derivation and validation of a novel right-sided heart failure model after implantation of continuous flow left ventricular assist devices: The EUROMACS (European Registry for Patients with Mechanical Circulatory Support) right-sided heart failure risk score.
      • Kavarana MN
      • Pessin-Minsley MS
      • Urtecho J
      • et al.
      Right ventricular dysfunction and organ failure in left ventricular assist device recipients: A continuing problem.
      • Al Shehri AM
      • El-Tahan MR
      • Al Metwally R
      • et al.
      Right ventricular function during one-lung ventilation: Effects of pressure-controlled and volume-controlled ventilation.
      • Rana M
      • Yusuff H
      • Zochios V.
      The right ventricle during selective lung ventilation for thoracic surgery.
      Among other culprits, insufficient cardioplegia, constrictive physiology, ischemia-reperfusion injury, excessive left ventricular unloading, pulmonary arterial hypertension, and increased RV afterload are possible causes of perioperative RVF in the aforementioned surgical settings.
      • Harjola VP
      • Mebazaa A
      • Celutkiene J
      • et al.
      Contemporary management of acute right ventricular failure: A statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology.
      • Zanobini M
      • Saccocci M
      • Tamborini G
      • et al.
      Postoperative echocardiographic reduction of right ventricular function: Is pericardial opening modality the main culprit?.
      • Bianco JC
      • Mc Loughlin S
      • Denault AY
      • et al.
      Heart transplantation in patients >60 years: Importance of relative pulmonary hypertension and right ventricular failure on midterm survival.
      • Soliman OII
      • Akin S
      • Muslem R
      • et al.
      Derivation and validation of a novel right-sided heart failure model after implantation of continuous flow left ventricular assist devices: The EUROMACS (European Registry for Patients with Mechanical Circulatory Support) right-sided heart failure risk score.
      • Kavarana MN
      • Pessin-Minsley MS
      • Urtecho J
      • et al.
      Right ventricular dysfunction and organ failure in left ventricular assist device recipients: A continuing problem.
      • Al Shehri AM
      • El-Tahan MR
      • Al Metwally R
      • et al.
      Right ventricular function during one-lung ventilation: Effects of pressure-controlled and volume-controlled ventilation.
      • Rana M
      • Yusuff H
      • Zochios V.
      The right ventricle during selective lung ventilation for thoracic surgery.
      “Injurious” (“high- pressure,” “high-volume,” and nonphysiologic “stress” and “strain”) invasive ventilation can result in or worsen RV dysfunction by increasing RV afterload and/or decreasing RV stroke index.
      • Mekontso-Dessap A
      • Boissier F
      • Charron C
      • et al.
      Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: Prevalence, predictors, and clinical impact.
      ,
      • Chiumello D
      • Chidini G
      • Calderini E
      • et al.
      Respiratory mechanics and lung stress/strain in children with acute respiratory distress syndrome.
      ,
      • Schmitt JM
      • Vieillard-Baron A
      • Augarde R
      • et al.
      Positive end-expiratory pressure titration in acute respiratory distress syndrome patients: Impact on right ventricular outflow impedance evaluated by pulmonary artery Doppler flow velocity measurements.
      Fig 1
      Fig 1Factors associated with right ventricular dysfunction and failure in surgical and nonsurgical settings.
      Abbreviations: ARDS, acute respiratory distress syndrome; CPB, cardiopulmonary bypass; CTEPH, chronic thromboembolic pulmonary hypertension; LVAD, left ventricular assist device; TACO, transfusion-associated circulatory overload; TRALI, transfusion-related acute lung injury
      In 2018, an ad hoc subcommittee of the American Thoracic Society Assembly on Pulmonary Circulation reviewed the literature and current state of knowledge relating to RV pathology, identified research gaps, and provided recommendations and pathways for progress.
      • Lahm T
      • Douglas IS
      • Archer SL
      • et al.
      Assessment of right ventricular function in the research setting: Knowledge gaps and pathways forward. An official American Thoracic Society Research Statement.
      The task force focused on the following three domains: (1) molecular and pathophysiologic mechanisms of RVF in different pulmonary hypertensive states; (2) invasive and noninvasive hemodynamic RV phenotyping at rest and in response to exercise and interventricular interactions; and (3) RV function assessment methodology.
      • Lahm T
      • Douglas IS
      • Archer SL
      • et al.
      Assessment of right ventricular function in the research setting: Knowledge gaps and pathways forward. An official American Thoracic Society Research Statement.
      In a state-of-the-art review, a group of recognized RV experts made the following additional clinical research recommendations for the critically ill2: (1) need for “at risk for RVF”, “early RVF,” and “RV dysfunction” definitions; (2) relationship between RV end-diastolic volume and distending pressure; (3) role of fluid removal in optimization of RV function and how to accurately assess intravascular volume status in RVF; and (4) the role of inodilators (eg, levosimendan) in improving right ventricle-pulmonary arterial coupling.
      • Vieillard-Baron A
      • Naeije R
      • Haddad F
      • et al.
      Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.
      Other important research areas are the “RV-protective” role of mechanical circulatory support (eg, venoarterial extracorporeal membrane oxygenation [ECMO] in acute RVF or venovenous ECMO) in acute respiratory distress syndrome and the natural history of RV dysfunction during ECMO support.
      There is a clear need for systematic “RV-protective” measures in patients with established RVF and strategies that mitigate RV “injury” in patients at risk of RVF and measures that potentially prevent progression of RV dysfunction to RVF. Despite established clinical, basic, and translational research in the area of RVF, the syndrome remains poorly understood and the uncertainties and knowledge gaps discussed urgently need to be addressed.
      • Vieillard-Baron A
      • Naeije R
      • Haddad F
      • et al.
      Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.
      The Protecting the Right Ventricle Network (PRORVNet) was established to improve the management of RVF in the critically ill.

      Protecting the Right Ventricle Network (PRORVNet). Available at: www.prorvnet.com. Accessed December 28, 2020.

      Its mission is to bring together clinical and industry investigators and conduct high-quality research into RV-protective strategies. The network started as a small UK initiative and now has the support of an international group of clinicians, scholars, and researchers with expertise in critical care medicine, cardiology, echocardiography, extracorporeal support, cardiothoracic surgery, and transplantation. Currently, the network has representation from 11 countries, with the aim of expanding. Together, the network's members will cultivate RV-centric research in the context of critical illness, surgery, and mechanical circulatory support.
      In order to develop strategies to protect the right ventricle, a strategic and phased plan will need to be followed. First must be the ability to identify patients who are at risk for or have developed RVF. This can occur through increased use of echocardiography, with a focus on standardizing the echocardiographic diagnosis and definition of RVF risk factors and grading the severity and hemodynamic sequelae of RVF (such as low cardiac output). The current research priority is to delineate the natural history, including both structurally and functionally, when RV dysfunction evolves, as well as compensatory RV adaptation and maladaptation in different physiologic states. This will allow for the testing of methods to determine how RVF is best detected, monitored, and measured. The network hopes to build on a scientific foundation and identify novel echocardiographic markers that can predict RVF and markers that can predict the potential for long-term RV recovery. The aim is to investigate the potential role of diagnostic modalities, such as pulmonary artery catheter with RV port (Paceport; Pace Analytical, Minneapolis, MN); disposable transesophageal probe (72 h); and near-infrared spectroscopy in the dynamic assessment of RV function and response to therapy.
      • Raymond M
      • Grønlykke L
      • Couture EJ
      • et al.
      Perioperative right ventricular pressure monitoring in cardiac surgery.
      The second priority is to determine, based on these markers, what is the optimal RV-protective treatment approach. This will be a combination of procedures, such as preload manipulation (volume loading, diuresis, or renal replacement therapy); optimizing contractility (including optimal heart rate and synchronous sinus rhythm targeting cardiac output); and reduction in RV afterload (lung-protective ventilation and pulmonary vasodilators). Goal-directed therapy optimizing each of these factors is most likely to result in optimization of the right ventricle. Consistent diagnosis of RVF, better prediction, and a group of goal-directed therapies have the highest possibility of improving the outcomes of patients with acute RVF.
      Other research plans are in place, and we welcome the opportunity for like-minded clinicians and investigators to reach out so that we can develop a strong evidence base through collaboration. Our role would be to facilitate the development of multicenter investigations into promising RV-protective strategies and therapies.

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