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

2021; Elsevier BV; Volume: 35; Issue: 6 Linguagem: Inglês

10.1053/j.jvca.2021.01.002

1532-8422

Vasileios Zochios, Gary Lau, Hannah Conway, Ken Kuljit S. Parhar,

Congenital Heart Disease Studies

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.1Vonk Noordegraaf A Chin KM Haddad F et al.Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: An update.Eur Resp J. 2019; 531801900Crossref PubMed Scopus (114) Google Scholar 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.1Vonk Noordegraaf A Chin KM Haddad F et al.Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: An update.Eur Resp J. 2019; 531801900Crossref PubMed Scopus (114) Google Scholar,2Vieillard-Baron A Naeije R Haddad F et al.Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.Intensive Care Med. 2018; 44: 774-790Crossref PubMed Scopus (52) Google Scholar RV failure (RVF) occurs when the right ventricle is unable to meet flow demands without excessive use of the Frank-Starling mechanism.2Vieillard-Baron A Naeije R Haddad F et al.Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.Intensive Care Med. 2018; 44: 774-790Crossref PubMed Scopus (52) Google Scholar 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.2Vieillard-Baron A Naeije R Haddad F et al.Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.Intensive Care Med. 2018; 44: 774-790Crossref PubMed Scopus (52) Google Scholar, 3Vonk-Noordegraaf A Haddad F Chin KM et al.Right heart adaptation to pulmonary arterial hypertension: Physiology and pathobiology.J Am Coll Cardiol. 2013; 62: D22-D33Crossref PubMed Scopus (533) Google Scholar, 4Meyer P Filippatos GS Ahmed MI et al.Effects of right ventricular ejection fraction on outcomes in chronic systolic heart failure.Circulation. 2010; 121: 252-258Crossref PubMed Scopus (198) Google Scholar, 5Kucher N Rossi E De Rosa M et al.Massive pulmonary embolism.Circulation. 2006; 113: 577-582Crossref PubMed Scopus (523) Google Scholar, 6Mekontso-Dessap A Boissier F Charron C et al.Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: Prevalence, predictors, and clinical impact.Intensive Care Med. 2016; 42: 862-870Crossref PubMed Scopus (175) Google Scholar, 7Sztrymf B Souza R Bertoletti L et al.Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension.Eur Respir J. 2010; 35: 1286-1293Crossref PubMed Scopus (167) Google Scholar, 8Hamon M Agostini D Le Page O et al.Prognostic impact of right ventricular involvement in patients with acute myocardial infarction: Meta-analysis.Crit Care Med. 2008; 36: 2023-2033Crossref PubMed Scopus (49) Google Scholar, 9Vanderpool RR Pinsky MR Naeije R et al.RV–pulmonary arterial coupling predicts outcome in patients referred for pulmonary hypertension.Heart. 2015; 101: 37-43Crossref PubMed Scopus (164) Google Scholar, 10Wardi G Blanchard D Dittrich T et al.Right ventricle dysfunction and echocardiographic parameters in the post-cardiac arrest patients: A retrospective cohort study.Resuscitation. 2016; 103: 71-74Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar RVF is multifactorial (Fig 1) and carries a high mortality.7Sztrymf B Souza R Bertoletti L et al.Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension.Eur Respir J. 2010; 35: 1286-1293Crossref PubMed Scopus (167) Google Scholar 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.11Price LC McAuley DF Marino PS et al.Pathophysiology of pulmonary hypertension in acute lung injury.Am J Physiol Lung Cell Mol Physiol. 2012; 302: L803-L815Crossref PubMed Scopus (70) Google Scholar, 12Zochios V Parhar K Tunnicliffe W et al.The right ventricle in ARDS.Chest. 2017; 152: 181-193Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar, 13Barnes T Zochios V Parhar K. Re-examining permissive hypercapnia in ARDS: A narrative review.Chest. 2018; 154: 185-195Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar It is contributed to by lung inflammation, pulmonary vascular dysfunction, and positive-pressure invasive ventilation.11Price LC McAuley DF Marino PS et al.Pathophysiology of pulmonary hypertension in acute lung injury.Am J Physiol Lung Cell Mol Physiol. 2012; 302: L803-L815Crossref PubMed Scopus (70) Google Scholar 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.14Vallabhajosyula 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.Ann Intensive Care. 2017; 7: 94Crossref PubMed Scopus (62) Google Scholar In RV infarction there are reduced RV contractility and right ventricle-pulmonary arterial uncoupling, leading to RVF.2Vieillard-Baron A Naeije R Haddad F et al.Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.Intensive Care Med. 2018; 44: 774-790Crossref PubMed Scopus (52) Google Scholar,15Harjola 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.Eur J Heart Fail. 2016; 18: 226-241Crossref PubMed Scopus (232) Google Scholar 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.15Harjola 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.Eur J Heart Fail. 2016; 18: 226-241Crossref PubMed Scopus (232) Google Scholar, 16Zanobini M Saccocci M Tamborini G et al.Postoperative echocardiographic reduction of right ventricular function: Is pericardial opening modality the main culprit?.Biomed Res Int. 2017; 20174808757Crossref PubMed Scopus (21) Google Scholar, 17Bianco 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.J Cardiothorac Vasc Anesth. 2018; 2: 32-40Abstract Full Text Full Text PDF Scopus (15) Google Scholar, 18Soliman 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.Circulation. 2018; 137: 891-906Crossref PubMed Scopus (89) Google Scholar, 19Kavarana MN Pessin-Minsley MS Urtecho J et al.Right ventricular dysfunction and organ failure in left ventricular assist device recipients: A continuing problem.Ann Thorac Surg. 2002; 73: 745-750Abstract Full Text Full Text PDF PubMed Scopus (248) Google Scholar, 20Al 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.J Cardiothorac Vasc Anesth. 2014; 28: 880-884Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar, 21Rana M Yusuff H Zochios V. The right ventricle during selective lung ventilation for thoracic surgery.J Cardiothorac Vasc Anesth. 2019; 33: 2007-2016Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar 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.15Harjola 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.Eur J Heart Fail. 2016; 18: 226-241Crossref PubMed Scopus (232) Google Scholar, 16Zanobini M Saccocci M Tamborini G et al.Postoperative echocardiographic reduction of right ventricular function: Is pericardial opening modality the main culprit?.Biomed Res Int. 2017; 20174808757Crossref PubMed Scopus (21) Google Scholar, 17Bianco 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.J Cardiothorac Vasc Anesth. 2018; 2: 32-40Abstract Full Text Full Text PDF Scopus (15) Google Scholar, 18Soliman 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.Circulation. 2018; 137: 891-906Crossref PubMed Scopus (89) Google Scholar, 19Kavarana MN Pessin-Minsley MS Urtecho J et al.Right ventricular dysfunction and organ failure in left ventricular assist device recipients: A continuing problem.Ann Thorac Surg. 2002; 73: 745-750Abstract Full Text Full Text PDF PubMed Scopus (248) Google Scholar, 20Al 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.J Cardiothorac Vasc Anesth. 2014; 28: 880-884Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar, 21Rana M Yusuff H Zochios V. The right ventricle during selective lung ventilation for thoracic surgery.J Cardiothorac Vasc Anesth. 2019; 33: 2007-2016Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar “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.6Mekontso-Dessap A Boissier F Charron C et al.Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: Prevalence, predictors, and clinical impact.Intensive Care Med. 2016; 42: 862-870Crossref PubMed Scopus (175) Google Scholar,22Chiumello D Chidini G Calderini E et al.Respiratory mechanics and lung stress/strain in children with acute respiratory distress syndrome.Ann Intensive Care. 2016; 6: 11Crossref PubMed Scopus (17) Google Scholar,23Schmitt 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.Crit Care Med. 2001; 29: 1154-1158Crossref PubMed Scopus (113) Google Scholar 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.24Lahm 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.Am J Respir Crit Care Med. 2018; 198: e15-e43Crossref PubMed Scopus (79) Google Scholar 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.24Lahm 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.Am J Respir Crit Care Med. 2018; 198: e15-e43Crossref PubMed Scopus (79) Google Scholar 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.2Vieillard-Baron A Naeije R Haddad F et al.Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.Intensive Care Med. 2018; 44: 774-790Crossref PubMed Scopus (52) Google Scholar 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.2Vieillard-Baron A Naeije R Haddad F et al.Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper.Intensive Care Med. 2018; 44: 774-790Crossref PubMed Scopus (52) Google Scholar The Protecting the Right Ventricle Network (PRORVNet) was established to improve the management of RVF in the critically ill.25Protecting the Right Ventricle Network (PRORVNet). Available at: www.prorvnet.com. Accessed December 28, 2020.Google Scholar 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.26Raymond M Grønlykke L Couture EJ et al.Perioperative right ventricular pressure monitoring in cardiac surgery.J Cardiothorac Anesth. 2019; 33: 1090-1104Abstract Full Text Full Text PDF Scopus (12) Google Scholar 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.