Mechanical Circulatory Support of the Failing Right Ventricle
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Mechanical circulatory support with extracorporeal life support (ECLS) can be considered as a bridge for patients with pulmonary arterial hypertension (PAH) and right ventricular (RV) failure. ECLS configurations like veno-venous ECMO can provide pulmonary support and veno-arterial ECMO can provide both pulmonary and cardiac support. Dynamic adjustments to PAH medications are required during ECLS due to changes in pharmacokinetics. ECLS can bridge patients to recovery if the RV failure is acute and reversible or to lung transplant if the patient is a transplant candidate. Experienced centers may have better outcomes with ECLS for PAH and RV failure.
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Mechanical Circulatory Support of the Failing Right Ventricle
- 1. Mechanical Circulatory Support of the Failing Right Ventricle Corey E. Ventetuolo, MD, MS, FAHA Associate Professor of Medicine, Departments of Medicine, Health Services Policy & Practice Associate Chief, Division of Pulmonary, Critical Care & Sleep Medicine Medical Director, Adult ECLS Program 15th Annual NC Research Triangle Pulmonary Hypertension Symposium November 17, 2023
- 2. Disclosures Consultant: Regeneron, Merck, Janssen Advisory boards: United Therapeutics, Merck, Janssen PI, Study Co-Chair: NHLBI funded clinical trials DSMBs: Elafin, H01/SATURN Intellectual bias: I believe ECLS works
- 3. Mechanical Circulatory Support for the RV I will not be talking about MCS for the RV in the context of LV failure, bridge to LVAD/heart transplant, or axial flow device Kapur, Circulation 2017
- 4. ECLS Alphabet Soup ECPR: Extracorporeal CardioPulmonary Rescusciation VA ECMO: Veno-Arterial ExtraCorporeal Membrane Oxygenation VV ECMO: Veno-Venous ExtraCorporeal Membrane Oxygenation ECCO2R: ExtraCorporeal CO2 Removal Triple and quadruple configurations Modifying traditional cardiopulmonary bypass circuit, outside of the OR Ventetuolo & Muratore, AJRCCM 2014
- 5. Two Consults for PH and Extracorporeal Life Support MICU Consult ARDS, low tidal volume ventilation Hemodynamically stable TTE: severe RV dilatation, severe dysfunction, septal flattening, RVSP 80 mm Hg OB/GYN Consult 30 yo connective tissue disease, 27 weeks pregnant Syncope RA 15, PA 82/45/57, PAOP 2, CO TD 2.15, PVR 26, PA sat 31% Rudder & Ventetuolo, NEJM 2021
- 6. Some Caveats Treating PH has become more complicated Treating PH + ECLS is even more complicated, and experiential These cases require multidisciplinary collaboration
- 7. ECLS in the Management of PAH: Not a Treatment but a Bridge To Recovery To Destination (Transplant) To Decision
- 8. Determine etiology and transplant candidacy Not a transplant candidate Transplant candidate ECMO as bridge to recovery ECMO as bridge to transplant • Progressive disease-related decompensation despite maximal medical therapy • Contraindication for ECMO • Acute decompensation due to treatable illness • Suboptimal medical management • No contraindication to ECMO Supportive care Optimize PAH therapy PT/OT, wean PAH therapy PAH with RV failure Adapted from Rosenzweig, ASAIO 2014 Destination first
- 9. Mullin & Ventetuolo, Clin Chest Med 2021 ? ECLS ? ECLS
- 10. PH/RV Failure and Extracorporeal Support Cardiac support CDH PPHN PAH PE Post-cardiotomy Pulmonary support Mild “secondary” PH ARDS VV-ECMO ECCO2R VA-ECMO Alternative configurations
- 11. Cardiac vs. Respiratory Configurations Ventetuolo & Muratore, AJRCCM 2014 VA-ECMO VV-ECMO Flow characteristics Non-pulsatile, low pulse pressure Non-pulsatile No recirculation Recirculation Hemodynamic support Partial to complete None LV effects Decreased preload None Increased afterload None Coronary oxygenation Native ejection (patient) ? Increased RV effects Decreased preload None Decreased afterload None Pulmonary Gas exchange Gas exchange Decreased pulmonary blood flow Unchanged
- 12. Use of ECLS to unload the RV and minimize deleterious effects on PVR Hypoxemia Hypercapnia Acidemia Mechanical ventilation Disselkamp, Annals ATS 2018
- 13. VV-ECMO: May have subtle effects on RV function Miranda, AJRCCM 2015 13 patients with acute respiratory failure No significant change in CI (TD) No change in pressor requirements 10 patients with ARDS Schmidt, Int Care Med 2013
- 14. Evidence that ECCO2R May be a Reasonable Approach in Select Patients with PH/RV Failure 5 patients with AECOPD Philipp, Muller, Int Care Med 2015
- 15. The REST Trial, ECCO2R McNamee, JAMA 2021 Serious Events 31% ECCO2R vs 9% control 4.5% ICH ECCO2R group
- 16. Approach to RV Failure in PAH Awake VA-ECMO Preload: diuresis RV ischemia: SBP>90, vasopressors Afterload: gas exchange, PAH therapy Contractility: inotrope Reverse triggers: optimize MV, treat infection Mullin & Ventetuolo, Clin Chest Med 2021 Medical optimization Preload: ultrafiltration RV ischemia: stop vasopressors Afterload: gas exchange, ± PAH therapy Contractility: stop inotrope Reverse triggers: awake
- 17. Six month survival after BLTx 80% awake ECMO vs 50% historical MV group (p = 0.02) Required shorter postoperative MV and hospital LOS 12% (MV) and 27% (awake) had PAH/CTEPH as underlying diagnosis (p=0.13) 24% (MV) and 42% (awake) had mPAP > 30 mm Hg (p=0.12) Am J Respir Crit Care Med 2012
- 18. There remains clinical equipoise for the use of ECMO in cardiogenic shock. PH/RV failure is an even larger gap. ECLS-SHOCK ECMO-CS Thiele, NEJM 2023 Ostadal, Circulation 2023
- 19. Appropriate candidate selection for VA-ECMO: SAVE-Score Parameters Score Diagnosis Myocarditis +3; VT/VF +2; post H/Ltx +3; congenital -3 Age 18-38 +7; ≥ 63 0 Weight (kg) 65-89 +2 Pre-ECMO organ failures Liver, CNS, Renal -3; CKD -6 Pre-ECMO duration intubation, hr 11-29 hrs -2; ≥ 30 hrs -4 PIP ≤ 20 mm Hg +3 Pre-ECMO cardiac arrest -2 Pre-ECMO DBP ≥ 40 mm Hg +3 Pre-ECMO pulse pressure ≤ 20mm Hg -2 Pre-ECMO HCO3 ≤ 15 mmol/L -3 Constant -6 Total SAVE Score -35 – +17 Schmidt, Eur Heart J 2015 There are no absolute contraindications for ECMO In PH, it is often bridge to decision
- 20. Determine etiology and transplant candidacy Not a transplant candidate Transplant candidate ECMO as bridge to recovery ECMO as bridge to transplant • Progressive disease-related decompensation despite maximal medical therapy • Contraindication for ECMO • Acute decompensation due to treatable illness • Suboptimal medical management • No contraindication to ECMO Supportive care Optimize PAH therapy PT/OT, wean PAH therapy PAH with RV failure Adapted from Rosenzweig, ASAIO 2014
- 21. Bridging to Recovery in PAH: Possible Clinical Scenarios PAH treatment naïve Newly diagnosed No parenteral therapy Pregnant Require surgery, procedure Volume overload Arrhythmia Sepsis Acute decompensation due to treatable illness Suboptimal medical management No contraindication to ECMO Optimize PAH therapy
- 22. Specific Considerations for PAH Therapies During ECLS Almost all are hepatically cleared Lipophilic Highly protein bound (91-99%) Very limited data suggests highly variable levels, efficacious dosages during ECLS PO sildenafil in 11 neonates (Ahsman, Arch Dis Child Fetal Neonatal Ed 2010) IV Treprostinil in 5 neonates (De Bie, Pharmacotherapy 2020) Flow through native pulmonary circulation will impact systemic effects Implant and explant, weaning Circuit changes Flow adjustments
- 23. PAH medications during ECLS: A different kind of recirculation
- 24. Dynamic Adjustments to PAH Therapy are Required during ECMO Torbic, J Cardiovasc Pharmacol Ther 2022
- 25. Determine etiology and transplant candidacy Not a transplant candidate Transplant candidate ECMO as bridge to recovery ECMO as bridge to transplant • Progressive disease-related decompensation despite maximal medical therapy • Contraindication for ECMO • Acute decompensation due to treatable illness • Suboptimal medical management • No contraindication to ECMO Supportive care Optimize PAH therapy PT/OT, wean PAH therapy PAH with RV failure Adapted from Rosenzweig, ASAIO 2014
- 26. Alternate configurations to support PAH patients bridging to transplant and recovery PA-LA, 2-3.5 L/min VV-ECMO + ASD with oxygenated shunt Upper body VA configuration Schmid, Ann Thorac Surg 2008 Strueber, Am J Transplant 2009 Rosenzweig, ASAIO 2014
- 27. Veno-pulmonary (OxyRVAD) and veno-veno-pulmonary configurations to support the RV Case series demonstrating possible RV protection in severe COVID-ARDS Case series using OxyRVAD as a bright to LTx in PH Concern for pulmonary overflow > high PVR > microhemorrhage Joyce, JTCVS 2021 Cain, J Surg Res 2021 Cain, JTCVS 2022 Mustafa, Ann Surg 2021 Lee, JHLT 2020 Usman, JCTS 2023
- 28. Increase in the use of prophylactic ECMO during lung transplant, LV reconditioning in PAH 21 (42%) had post-operative LV dysfunction 26 (52%) required ECMO Increasing use of prophylactic ECMO over study period 48/50 (96%) survived Otto, Crit Care 2022; Tudorache, Transplantation 2015; Pereszlenyi, Eur J Cardio-thorac Surg, 2002; Ko, Artificial Organs 2001; Ko, Transpl Proc 1999
- 29. Awake ECMO after lung transplantation in PAH for LV reconditioning Tudorache, Transplantation 2015 Pereszlenyi, Eur J Cardio-thorac Surg, 2002 Ko, Artificial Organs 2001 Ko, Transpl Proc 1999
- 30. Role of ECMO in Management of PAH IIa: Should be considered C: Consensus, small/retrospective studies
- 31. Experienced centers may have better outcomes Freeman, CCM 2014 Karamlou, J Thorac Cardiovasc Surg 2013 Barbaro, Am J Respir Crtic Care Med 2015 Hayes, Am J Respir Crtic Care Med 2016
- 32. Two Consults for PH and Extracorporeal Life Support MICU Consult ARDS, low tidal volume ventilation Hemodynamically stable TTE: severe RV dilatation, severe dysfunction, septal flattening, RVSP 80 mm Hg OB/GYN Consult 30 yo connective tissue disease, 27 weeks pregnant Syncope RA 15, PA 82/45/57, PAOP 2, CO TD 2.15, PVR 26, PA sat 31% Rudder & Ventetuolo, NEJM 2021 VV-ECMO or Veno-Pulmonary VA-ECMO
- 33. Durable support for the RV in PH?
- 34. Durable support for the RV in PH?
- 35. Take Home Points: ECLS for the Failing RV Determine etiology and plan for bridge Involve PH team, multidisciplinary collaboration Beware systemic vasodilation and “recirculation” Dynamic adjustments in PAH therapy (IV/inhaled) when BTR Awake VA-ECMO is “standard” Novel configurations, much more to learn, durable support may be possible
- 36. Thanks to the team!
- 37. Acknowledgments Patients and families who participate in research Funding: AHA, 11FTF7400032 NIH, P20 GM103652 NHLBI, R01 HL141268 Parker B. Francis (Adeel Abbasi) Brown University James Klinger Elizabeth Harrington Christopher Mullin Navneet Singh Katherine Cox- Flaherty Mary Whittenhall Britt Ferland Kayla Thatcher Rachel Sanders Grayson Baird Carsten Eickhoff Mandy Pereira Amy Princiotto Adeel Abbasi
Editor's Notes
- 13 subjects with acute resp failure PA catheter 6 hours after cannulation Two patients awaiting transplant; mPAP 26 and 43 mm Hg before ECMO No significant change in CI No change in pressors CI measured by TD
- Acute, potentially reversible cause of moderate to severe hypoxemic respiratory failure MV > 5 PEEP, within 48 hrs of PaO2/FiO2 < 150 Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5%in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5%in the standard care group (risk ratio, 1.05 [95%CI, 0.83-1.33]; difference, 2.0%[95%CI, −7.6%to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95%CI, 5.9-8.3] vs 9.2 [95%CI, 7.9-10.4] days; mean difference, −2.1 [95%CI, −3.8 to −0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. CONCLUSIONS AND RELEVANCE The secondary outcomes are presented in Table 2. Therewere significantly fewer ventilator-free days at day 28 in the intervention group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days;meandifference,−2.1days [95%CI,−3.8to−0.3];P = .02). There was no significant between-group difference in duration of ventilation,needforECMOat day 7, mortality at28days, or duration of ICU or hospital stay.
- In this multicenter trial, patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization was planned were randomly assigned to receive early ECLS plus usual medical treatment (ECLS group) or usual medical treatment alone (control group). The primary outcome was death from any cause at 30 days. Safety outcomes included bleeding, stroke, and peripheral vascular complications warranting interventional or surgical therapy. RESULTS A total of 420 patients underwent randomization, and 417 patients were included in final analyses. At 30 days, death from any cause had occurred in 100 of 209 patients (47.8%) in the ECLS group and in 102 of 208 patients (49.0%) in the control group (relative risk, 0.98; 95% confidence interval [CI], 0.80 to 1.19; P=0.81). The median duration of mechanical ventilation was 7 days (interquartile range, 4 to 12) in the ECLS group and 5 days (interquartile range, 3 to 9) in the control group (median difference, 1 day; 95% CI, 0 to 2). The safety outcome consisting of moderate or severe bleeding occurred in 23.4% of the patients in the ECLS group and in 9.6% of those in the control group (relative risk, 2.44; 95% CI, 1.50 to 3.95); peripheral vascular complications warranting intervention occurred in 11.0% and 3.8%, respectively (relative risk, 2.86; 95% CI, 1.31 to 6.25). CONCLUSIONS In patients with acute myocardial infarction complicated by cardiogenic shock with planned early revascularization, the risk of death from any cause at the 30-day follow-up was not lower among the patients who received ECLS therapy than among those who received medical therapy alone. (Funded by the Else Kröner Fresenius Foundation and others; ECLS-SHOCK ClinicalTrials.gov numb In the ECMO-CS trial (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock), immediate implementation of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) did not improve outcomes compared with no immediate VA-ECMO in patients with severe or rapidly deteriorating cardiogenic shock. ● A large proportion (39%) of patients in the no early VA-ECMO group subsequently received VA-ECMO or other mechanical circulatory support because of further hemodynamic deterioration. What Are the Clinical Implications? ● Even in patients with severe or rapidly deteriorating cardiogenic shock, early hemodynamic stabilization using inotropes and vasopressors with implementation of mechanical circulatory support only in case of further hemodynamic deterioration provided outcomes that were not different from immediate insertion of VA-ECMO
- Extracorporeal membrane oxygenation (ECMO) may provide mechanical pulmonary and circulatory support for patients with cardiogenic shock refractory to conventional medical therapy. Prediction of survival in these patients may assist in management of these patients and comparison of results from different centers. AIMS: To identify pre-ECMO factors which predict survival from refractory cardiogenic shock requiring ECMO and create the survival after veno-arterial-ECMO (SAVE)-score. METHODS AND RESULTS: Patients with refractory cardiogenic shock treated with veno-arterial ECMO between January 2003 and December 2013 were extracted from the international Extracorporeal Life Support Organization registry. Multivariable logistic regression was performed using bootstrapping methodology with internal and external validation to identify factors independently associated with in-hospital survival. Of 3846 patients with cardiogenic shock treated with ECMO, 1601 (42%) patients were alive at hospital discharge. Chronic renal failure, longer duration of ventilation prior to ECMO initiation, pre-ECMO organ failures, pre-ECMO cardiac arrest, congenital heart disease, lower pulse pressure, and lower serum bicarbonate (HCO3) were risk factors associated with mortality. Younger age, lower weight, acute myocarditis, heart transplant, refractory ventricular tachycardia or fibrillation, higher diastolic blood pressure, and lower peak inspiratory pressure were protective. The SAVE-score (area under the receiver operating characteristics [ROC] curve [AUROC] 0.68 [95%CI 0.64-0.71]) was created. External validation of the SAVE-score in an Australian population of 161 patients showed excellent discrimination with AUROC = 0.90 (95%CI 0.85-0.95). CONCLUSIONS: The SAVE-score may be a tool to predict survival for patients receiving ECMO for refractory cardiogenic shock (www.save-score.com).
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- End-stage PH Ltx Alfred Hospital Retrospective LV dysfunction decrement in EF by 15%
- After transplant, normalized LV preload 23 BLTx patients – severe PAH, sarcoid, IPAH, CTEPH PVR 1400 dynes, RVEF 34%, CI 2, mPAP 66 prior 100% 90 day survival Severe PH > LV diastolic dysfunction from small, stiff LVs > early PGD