On the Right Path: Predicting Right Ventricular Failure After Left Ventricular Assist Device : ASAIO Journal

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Invited Commentary

On the Right Path: Predicting Right Ventricular Failure After Left Ventricular Assist Device

Sayer, Gabriel; Rubinstein, Gal; Uriel, Nir

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ASAIO Journal 69(1):p 82-85, January 2023. | DOI: 10.1097/MAT.0000000000001880
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Left ventricular assist devices (LVAD) are a widely used treatment for advanced heart failure with 5 year survival close to 60%.1 However, the overall use of LVAD therapy is declining, possibly related to changes in the heart transplant allocation system as well as concern about post-LVAD morbidities that occur in the perioperative period and during long-term use of the device. Right ventricular failure (RVF) is a common complication follow LVAD implantation that often occurs in the early postimplant period, whereas there is increasing recognition of late RVF, presenting later in the course of LVAD therapy. In the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) trial, early RVF was reported to occur in 34% of patients.2 This incidence rate is in line with multiple single-center reports as well as recent data from the Interagency Registry of Mechanical Circulatory Support (INTERMACS) showing a rate of RVF of 37% at 2 years.3

Numerous studies have tried to understand risk factors for the development of post-LVAD RVF (Table 1).4–16 These studies have focused on preoperative factors, including demographics, clinical status, laboratory data, imaging, and hemodynamics. Some studies have focused on single predictive factors, whereas others have taken a multiparametric approach. These scores have demonstrated varying degree of accuracy. A high predictive value has been achieved in some single-center studies focusing on advanced imaging techniques, whereas risk scores from larger cohorts that are more broadly applicable have only achieved moderate predictive value. As a result, no score or parameter has achieved widespread adoption, and efforts to further refine the identification of risk for post-LVAD RVF continue.

Table 1. - Representative Studies Evaluating Predictors of Post-LVAD Right Ventricular Failure
Category Study N Device RVF Definition RVF% Parameter Studied Results
 Imaging Kukucka, 2011 115 HeartMate II, BerlinHeartIncor RVAD or 2 hemodynamic criteria (MAP, RAP MVO2, CI) 13% Ratio of RV to LV end-diastolic diameter Ratio of ≥ 0.72 had AUROC 0.74, odds ratio for RVF 11.4
Grant, 2012 117 HeartMate II, HVAD RVAD or inotropes > 14 days 40% RV free wall longitudinal strain Lower strain in RVF group (–9.0% vs. –12.2%)
AUROC of strain + Michigan risk score: 0.77
Kato, 2013 68 HeartMate II, HVAD RVAD or inotropes > 14 days or iNO>48 hr 35% Tissue Doppler and RV longitudinal strain Lower RV strain in RVF group (–12.6% vs. –16.2%)
AUROC for tissue doppler + RV strain: 0.77
Kiernan, 2015 24 HeartMate II, HVAD RVAD or inotropes > 14 days 46% 3D echocardiography AUROC for RV end-diastolic volume index: 0.90
AUROC for RV end-systolic volume index: 0.88
Scott, 2023 20 HeartMate 3, HVAD RVAD or inotropes > 14 days with RAP >15 35% Gated 3D cine CT AUROC for RV end-diastolic volume index: 0.79
AUROC for RV end-systolic volume index: 0.76
Hemodynamics Dang, 2006 108 HeartMate XVE RVAD or inotropes > 14 days 39% Intraoperative RAP RAP in RVF vs. non-RVF: 23.2 vs. 17.4
Kormos, 2010 484 HeartMate II RVAD, inotropes>14 days 20% Ratio of RAP/PCWP RAP/PCWP odds ratio for RVF: 2.3, p=0.009
Morine, 2016 132 HeartMate II, HVAD RVAD or inotropes > 14 days 24% Pulmonary Artery Pulsatility Index PAPi lower in patients with RVF (1.32 vs. 2.77)
AUROC for PAPi<1.85: 0.942
Kang, 2016 85 HeartMate II, HVAD RAP > 18 with CI < 2 and PCWP<18 or RVAD or iNO > 1 wk 33% Pulmonary Artery Pulsatility Index Odds ratio for RVF 0.76 for each 1 point increase in PAPi
Multiparametric Matthews, 2008 197 HeartMate XVE,
HeartMate II, IVAD, Novacor
RVAD or inotropes > 14 days, or iNO >48 hr 35% Vasopressor, AST ≥ 80, Bilirubin >2.0, Cr > 2.3 Likelihood ratio for low risk 0.49
Likelihood ratio for high risk 7.6
Fitzpatrick, 2008 266 HeartMate XVE, BVS-5000, PVAD,
HeartMate II, TCI IP
Need for RVAD 37% Cardiac Index < 2.2, RVSWI < 0.25, severe RV dysfunction, Cr > 1.9, prior surgery, SBP<96 Risk score: sensitivity 83%, specificity 80%
Atluri, 2013 218 HVAD, HeartMate II, HeartMate XVE, BVS-5000, PVAD, VentrAssist Need for RVAD 23% RAP>15, severe RV dysfunction by echo, intubation, severe TR, HR>100 AUROC for risk score: 0.8
Soliman, 2017 2,988 HVAD, HeartMate II, HM3 RVAD or inotropes > 14 days, or iNO >48 hr 22% INTERMACS 1-3, multiple inotropes, severe RV dysfunction by echo, RAP/PCWP 0.54, Hgb<10 AUROC for risk score: 0.70
3D, three-dimensional; AST, aspartate aminotransferase; AUROC, area under the ROC curve; CI, cardiac index; Cr, creatinine; CT, computed tomography; Hgb, hemoglobin; HR, heart rate; iNO, inhaled nitric oxide; INTERMACS, Interagency Registry for Mechanically Assisted Circulatory Support; LV, left ventricular; MAP, mean arterial pressure; MVO2, mixed venous oxygen saturation; PAPi, pulmonary artery pulsatility index; PCWP, pulmonary capillary wedge pressure; RAP, right atrial pressure; RV, right ventricular; RVAD, right ventricular assist device; RVF, right ventricular failure; RVSWI, right ventricular stroke work index; SBP, systolic blood pressure; TR, tricuspid regurgitation.

In this context, the study in this issue of ASAIO Journal by Scott et al., investigates a new technique to evaluate the right ventricle before LVAD implantation.8 The authors evaluate the predictive ability of volumetric and functional assessment by contrast-enhanced electrocardiogram-gated computed tomography angiography. This proof-of-concept analysis of 20 patients demonstrates that preoperative right ventricular (RV) volumes are markedly enlarged in patients who develop RVF in this cohort compared to those without RVF (RV end-diastolic volume index 162 ± 43 ml/m2vs. 112 ± 37 ml/m2, p = 0.007), whereas the authors did not find a statistically significant difference in RV stroke volume index or RV ejection fraction between the two groups. This study introduces an interesting parameter that should be evaluated in a larger cohort to better understand its validity. Further work is needed to characterize how this volumetric measurement responds to alterations of preload and afterload, and clarify whether this measurement provides intrinsic information about underlying RV structure and function, or whether it more closely reflects the severity of volume overload, a factor that should be manageable over time with LVAD therapy.

The existence of a large number of risk scores with significant diversity of parameters is indicative of the complex nature of RVF in this population (Figure 1). The pathophysiology of RVF can be divided into preoperative, intraoperative, and postoperative factors. The current study focuses on the status of the right ventricle in the preoperative period, supporting the theory that much of what drives RVF is baseline RV structure and function. However, intraoperative and postoperative factors can also play a significant role in the development of RVF. In particular, intraoperative RV insult related to surgical technique (sternotomy vs. thoracotomy), vasoplegia, blood product utilization, and cardiopulmonary bypass can alter the perioperative course and lead to RVF. Postoperatively, RV function is impacted by the hemodynamics of ventricular interdependence. The left and right ventricle work in parallel because of the shared interventricular septum, and the LVAD disrupts the normal hemodynamic milieu by altering the position of the septum. An additional challenge is that these ventricles also work in series with changes in preload and afterload of each ventricle causing downstream or upstream effects in the other ventricle. Because of complex nature of these interactions, it is unlikely that a single parameter will be able to account for all of the potential mechanisms of postoperative RVF.

F1
Figure 1.:
Schematic representation of the large number of risk scores with significant diversity of parameters is indicative of the complex nature of right ventricular failure in the left ventricular assist device patient population.

Both volume measurements and pressure measurements provide valuable information about cardiac pathophysiology, but whether one is superior for assessing homeostasis in the heart failure patient remains a topic of debate. Along with a previous study of three-dimensional echocardiography the current study by Scott et al. provide evidence of strong predictive value obtained that can be from volumetric measurements. In general, changes in intracardiac volume are thought to precede changes in intracardiac pressure. The finding here of the important predictive value of a volumetric measurement supports the idea that these early changes may be more indicative of the current clinical performance of the right ventricle than more commonly used pressure measurements. Perhaps the most important message of this study is to give equal consideration to volume measurements as we do currently to pressure measurements when trying to assess overall risk for RVF in LVAD patients.

Finally, it is important to recognize that prediction of RVF will never be a perfect art. Currently identified preoperative parameters and risk scores may have reached the most accuracy that can reasonably be achieved in this population. Using the available data, each center can choose the parameters or scores that work best given local testing availability, whereas acknowledging that they will not be able to identify all cases of RVF upfront. Furthermore, how to use the information in risk scores is not fully understood, as many patients with early RVF will not go on to have chronic RVF, and therefore these scores should not be used to exclude all high-risk patients from LVAD therapy, but rather to focus attention on developing best management strategies for RVF when it does occur.

References

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Keywords:

LVAD; right ventricle; right ventricular failure

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