Editor's Note
The late-breaking presentation by Soliman et al. at the European Society of Cardiology Congress 2017 stimulated a discussion of the assessment and importance of the right ventricular response to continuous flow left ventricular assist devices. Drs. Morine, Annamalai, and Kapur have provided a succinct commentary on not just on the presentation but on the overall issue.
By George W. Vetrovec, MD, MACC
Editorial Team Lead, Invasive Cardiovascular Angiography & Interventions collection on ACC.org
Richmond, VA

Right ventricular (RV) failure consistently worsens clinical outcomes among patients with heart failure (HF), acute myocardial infarction (AMI), and pulmonary hypertension. Over the past decade, massive growth in the use of continuous flow left ventricular assist devices (LVAD) has unmasked a unique population of patients with advanced HF who develop RV failure after insertion of a continuous flow LVAD. Development of RV failure after continuous flow LVAD implantation occurs due to anatomic changes in biventricular geometry after apical coring and LVAD activation; increased venous return to the RV, which can cause volume overload; and perioperative stressors such as bleeding, hypoxemia, and volume shifts that can increase RV afterload. Consequences of post-LVAD RV failure include increased mortality and impaired quality of life. Furthermore, the risk of RV failure becomes prohibitive when evaluating patients for continuous flow LVAD therapy as part of a destination therapy strategy for whom an RV assist device is not an option.

For these reasons, prevention of RV failure after continuous flow LVAD surgery is a major unmet clinical need. Reliable prediction of post-operative RV failure remains challenging despite the development of risk scores incorporating demographic, laboratory, hemodynamic, and echocardiographic pre-operative variables.^1-5 In the largest study to date, Soliman and colleagues investigated predictors of post-operative RV failure among nearly 3,000 recipients of contemporary continuous flow LVAD in EUROMACS (European Registry for Patients with Mechanical Circulatory Support) and generated a five-variable risk score incorporating INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) class, use of inotropes, severe RV dysfunction by echocardiogram, ratio of right atrial/pulmonary capillary wedge pressure and hemoglobin. They identified that post-operative RV failure was associated with increased all-cause mortality and that the EUROMACS risk score stratified risk of post-operative RV failure from low (score 0-2; 11%) to high (score >4; 43%). The definition of post-operative RV failure used by the authors and the reported incidence of post-operative RV failure of 20% are consistent with prior reports from continuous flow LVAD clinical trials and other retrospective analyses. Furthermore, the EUROMACS analysis includes a validation cohort derived from a subset EUROMACS that strengthens their findings. There are differences between EUROMACS and INTERMACS, such as INTERMACS classification prior to continuous flow LVAD surgery and the proportion of patients receiving continuous flow LVAD for destination therapy, which may affect post-operative RV failure. However, the authors' robust statistical approach, impressive sample size, and inclusion of current era continuous flow LVAD are major contributions toward improved prediction of post-operative RV failure.

Soliman et al. made several unique observations regarding the relationship between pre-operative variables and post-operative RV failure. This study confirms with a larger sample size prior observations that different continuous flow LVAD platforms are associated with different incidences of post-operative RV failure.⁵ This may relate to patient-specific rather than device-specific factors in the absence of randomization, but this finding may suggest that the unique hemodynamic profile of continuous flow LVAD design may affect the development of post-operative RV failure. Continuous flow LVAD platform-specific management considerations and risk scores may be merit further investigation. The authors identified anemia as an important predictor of post-operative RV failure. The etiology of anemia in advanced HF is multifactorial and includes multisystem dysfunction and aberrant iron metabolism. Given the accumulating evidence that iron repletion provides functional benefit in selected patients with HF with and without anemia, examination of the iron status of patients prior to LVAD surgery is warranted. Anemia and iron depletion may be modifiable risk factors for post-operative RV failure.

Management of severe RV failure in patients considered for continuous flow LVAD implantation includes durable biventricular mechanical support or orthotopic heart transplantation. Soliman et al. and previous studies have shown that less-than-severe RV dysfunction is common prior to continuous flow LVAD surgery. Intriguingly, the variables included in the EUROMACS-RHF risk score are plausibly related to RV dysfunction, suggesting that the presence of RV dysfunction in advanced LV failure may be the critical pre-operative "risk factor" for the development of post-operative RV failure. Of interest would be further investigation of RV function and RV and pulmonary artery (PA) coupling using novel hemodynamic measures to identify patients with RV dysfunction who may benefit from intervention prior to and during the peri-operative setting.⁶ We reported the PA pulsatility index (the ratio of PA pulse pressure divided by right atrial pressure) as a simple hemodynamic formula that identifies RV failure after AMI and continuous flow LVAD implantation.^5,11 Other formulas to assess RV-PA hemodynamics include pulmonary vascular resistance, diastolic pulmonary gradient, PA elastance, PA compliance, and PA impedance.^13-17 Although a single formula does not define RV failure, incorporation of hemodynamics into clinical decision-making algorithms is an area of ongoing research.

If the risk of post-LVAD RV failure can be recognized pre-operatively using a risk score or other predictive metric, there may be an opportunity to mitigate the development of post-operative RV failure. Medical management includes optimization of RV preload, afterload, and inotropic support. More recently, percutaneous acute mechanical circulatory support devices for RV failure include venoarterial extracorporeal membrane oxygenation, the TandemHeart (CardiacAssist, Inc.; Pittsburgh, PA) centrifugal-flow pump, and the axial-flow Impella RP (Abiomed; Danvers, MA) catheter.^7-9 In 2015, the prospective RECOVER-RIGHT (The Use of Impella RP Support System in Patients With Right Heart Failure) trial demonstrated for the first time that the Impella RP for RV failure following AMI or cardiac surgery was safe, provided hemodynamic benefit, and was associated with favorable clinical outcomes.¹⁰ This study led to the recent approval of the Impella RP device by the Food and Drug Administration for use as an RV support device for RV failure. Utilization of the EUROMACS risk score to identify patients at risk of post-operative RV failure may allow for the institution of medical or mechanical therapy prior to surgery to protect the RV from the hemodynamic and anatomic alterations that occur after continuous flow LVAD implantation. The study by Soliman et al. is an important step toward an era of a proactive rather than reactive approach to RV failure in continuous flow LVAD recipients.

References

1. Kirklin JK, Pagani FD, Kormos RL, et al. Eighth annual INTERMACS report: Special focus on framing the impact of adverse events. J Heart Lung Transplant 2017;36:1080-86.
2. Matthews JC, Koelling TM, Pagani FD, Aaronson KD. The right ventricular failure risk score a pre-operative tool for assessing the risk of right ventricular failure in left ventricular assist device candidates. J Am Coll Cardiol 2008;51:2163-72.
3. Fitzpatrick JR 3rd, Frederick JR, Hsu VM, et al. Risk score derived from pre-operative data analysis predicts the need for biventricular mechanical circulatory support. J Heart Lung Transplant 2008;27:1286-92.
4. Atluri P, Goldstone AB, Fairman AS, et al. Predicting right ventricular failure in the modern, continuous flow left ventricular assist device era. Ann Thorac Surg 2013;96:857-63.
5. Morine KJ, Kiernan MS, Pham DT, Paruchuri V, Denofrio D, Kapur NK. Pulmonary Artery Pulsatility Index Is Associated With Right Ventricular Failure After Left Ventricular Assist Device Surgery. J Card Fail 2016;22:110-6.
6. Kapur NK, Esposito ML, Bader Y, et al. Mechanical Circulatory Support Devices for Acute Right Ventricular Failure. Circulation 2017;136:314-26.
7. Kapur NK, Paruchuri V, Korabathina R, et al. Effects of a percutaneous mechanical circulatory support device for medically refractory right ventricular failure. J Heart Lung Transplant 2011;30:1360-7.
8. Kapur NK, Paruchuri V, Jagannathan A, et al. Mechanical circulatory support for right ventricular failure. JACC Heart Fail 2013;1:127-34.
9. Truby L, Mundy L, Kalesan B, et al. Contemporary Outcomes of Venoarterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock at a Large Tertiary Care Center. ASAIO J 2015;61:403-9.
10. Anderson MB, Goldstein J, Milano C, et al. Benefits of a novel percutaneous ventricular assist device for right heart failure: The prospective RECOVER RIGHT study of the Impella RP device. J Heart Lung Transplant 2015;34:1549-60.
11. Korabathina R1, Heffernan KS, Paruchuri V, et al. The pulmonary artery pulsatility index identifies severe right ventricular dysfunction in acute inferior myocardial infarction. Catheter Cardiovasc Interv 2012;80:593-600.
12. Drakos SG, Janicki L, Horne BD, et al. Risk factors predictive of right ventricular failure after left ventricular assist device implantation. Am J Cardiol 2010;105:1030-5.
13. Aschauer S, Kammerlander AA, Zotter-Tufaro C, et al. The right heart in heart failure with preserved ejection fraction: insights from cardiac magnetic resonance imaging and invasive haemodynamics. Eur J Heart Fail 2016;18:71-80.
14. Handoko ML, De Man FS, Oosterveer FP, Bogaard HJ, Vonk-Noordegraaf A, Westerhof N. A critical appraisal of transpulmonary and diastolic pressure gradients. Physiol Rep 2016;4:e12910.
15. Dupont M, Mullens W, Skouri HN, et al. Prognostic role of pulmonary arterial capacitance in advanced heart failure. Circ Heart Fail 2012;5:778-85.
16. Amin A, Taghavi S, Esmaeilzadeh M, Bakhshandeh H, Naderi N, Maleki M. Pulmonary arterial elastance for estimating right ventricular afterload in systolic heart failure. Congest Heart Fail 2011;17:288-93.
17. Vonk Noordegraaf A, Westerhof BE, Westerhof N. The Relationship Between the Right Ventricle and its Load in Pulmonary Hypertension. J Am Coll Cardiol 2017;69:236-43.

Keywords: ESC Congress, ESC2017, Heart-Assist Devices, Risk Factors, Pulmonary Wedge Pressure, Extracorporeal Membrane Oxygenation, Atrial Pressure, Blood Pressure, Pulmonary Artery, Electric Impedance, Heart Failure, Heart Transplantation, Ventricular Dysfunction, Right, Diastole, Echocardiography, Hypertension, Pulmonary, Anemia, Vascular Resistance, Hemoglobins, Myocardial Infarction, Algorithms, Angiography

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