http://www.jhltonline.org
EDITORIAL COMMENTARIES
The right heart failure dilemma in the era of left ventricular assist devices Robert L. Kormos, MD From the Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
“In acute diseases it is not quite safe to prognosticate either death or recovery.” “If an operation is considered necessary, one should act at the beginning. “Once the illness has reached a peak, it is best left alone.”—Hippocrates: Aphorisms The challenges presented to clinicians by the failing right ventricle (RV) precede our most recent experiences with left ventricular assist devices (LVADs) by decades, yet for a multitude of reasons we seem not to have solved this difficult dilemma. The LVAD is both beneficial and detrimental to the RV. It is beneficial by reducing the RV’s work against pressure by decompressing the LV and thus the pulmonary capillary wedge pressure, which in turn passively reduces pulmonary vascular resistance. On the other hand, an LVAD, by decompressing the LV, can cause a leftward shift of the interventricular septum, which results in a more spherical shape to the RV, thus disadvantaging it in its mechanical contractile properties. In addition, a new set of hemodynamic conditions is presented to the RV. Whereas RV output had been equated to the LV output, once we have introduced an LVAD we raise the expected output of the RV to that of the LVAD. RV-developed pressure is determined by RV free wall function, LV function and interventricular septal position and function. Once the septum has been essentially disabled, the work becomes the responsibility of the anterior free wall of the RV. Thus, the anatomic, functional and physiologic parameters imposed upon the RV by an LVAD create a set of conditions whereby the RV operates in a disadvantaged mechanical zone, thus relying largely on a reduction in pulmonary after-load for its most of its operability. A delicate balance between adequate decompression and pump flow required for end-organ perfusion must be in place while protecting RV anatomic integrity. This produces what I refer to as the RV dilemma. Much of the early morbidity and mortality associated with LVADs relates to patient selection. INTERMACS clearly delineates the key effect of the selection of Level 1 patients upon peri-operative mortality and long-term outcome.1 Thus, although multiple parameters have evolved for assessing the
hemodynamic and echocardiographic risk factors for RV failure after LVAD use, many of these can be rendered less predictive by an overwhelming set of clinical conditions of acuity, pre-operative end-organ failure and cardiogenic shock, which ultimately translate into an inflammatory state that affects both RV contractility and pulmonary function. The role of the lung and its pathology and response to acute injury of surgery and shock has been under-recognized for its contribution to total pulmonary resistance, which can reduce the benefit that the LVAD provides in reducing the pulmonary after-load. We are therefore often driven to LVAD implantation in a subset of patients by the acuity of implantation. The percentage of patients presenting with acute cardiogenic shock is likely to grow as temporary percutaneous strategies of circulatory support become more widely applied in conditions of acute myocardial compromise and as centers become more comfortable with extracorporeal membrane oxygenation. In this issue of the journal, Takeda and colleagues report on their experience with the unplanned use of a right ventricular assist device (RVAD) in patients receiving a LVAD.2 Of 398 patients, 44 (11%) required a RVAD—over 64% of which were placed at the same operative setting and another 36% within 3 days of LVAD implantation. However, it is also important to note that another 9% of the total group had elective biventricular assist devices (BiVADs) implanted, thus revealing that 20% of the patients had a recognized or unrecognized risk for RV failure. Only 48% of the unplanned RVAD-supported patients could be weaned from their device. Again, in their study, as in others, the pre-implant clinical factors, such as level of end-organ failure, seemed to outweigh the more evidence-based rationale for selecting an LVAD alone according to echocardiographic or hemodynamic predictors. The early peri-operative outcomes also seem to support the strategy that a planned BiVAD implant has lower hospital mortality (30%) compared with use of an unplanned RVAD (50%). In many ways, Takeda et al confirm a prejudice that is rapidly growing in the mechanical support community. Many physicians have accepted RV failure as a necessary
1053-2498/$ - see front matter r 2014 International Society for Heart and Lung Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.healun.2013.12.019
Kormos
The Right Heart Failure Dilemma in the Era of Left Ventricular Assist Devices
evil of mechanical circulatory support and have grown to accept the morbidity and mortality associated with the needs for its use. This has led to the development of RVAD technologies that are based upon percutaneous solutions which may lead to earlier adoption of RVAD support. Clearly, the outcome of any of these solutions will have to be proven to be of benefit; currently, we are still faced with 50% mortality—and that merely addresses the population in whom RV failure was obvious due to the need for an RVAD. It does not address the larger population in whom inotropic support may be required for weeks to months after LVAD implantation. This subset of patients with RV dysfunction after LVAD may be over 2-fold larger than the subset requiring a RVAD.3,4 If we consider methods to reduce the risk of RV failure after LVAD implantation, the pre-operative optimization should then be focused on judicious inotropic support combined with efforts to reduce the loading conditions for the RV through aggressive diuresis and, if necessary, temporary use of an intra-aortic balloon pump. The goals are to improve end-organ perfusion to reduce the risk of multi-organ dysfunction, including pulmonary congestion, and to thereby optimize the RV. Intra-operatively, surgical techniques focus on proper pump positioning in the LV and avoidance of bleeding, hypotension, acidosis and volume overload. Overzealous product transfusion due to bleeding results in transfusion-related lung injury, which increases the total pulmonary resistance, again straining the RV. The maintenance of mean arterial pressure is critical for RV perfusion, but also prevents LV collapse due to overly aggressive LV unloading in the presence of low systemic after-load. Other medical strategies include ventilation, which reduces carbon dioxide while optimizing oxygen delivery. Reports of temporary right atrial to pulmonary artery bypass as an extension of the main cardiopulmonary bypass circuit while weaning from bypass have been shown to help gradually reintroduce the workload to the RV. It is critical to realize that clinicians are not enamored with using long-term BiVAD support or its alternative, the total artificial heart. The most recent INTERMACS5 data demonstrate that in 49,000 patients only 2% received a total artificial heart and another 5.7% received a BiVAD implant. It is even more telling that, before 2010, 11.8% of patients received a BiVAD and, in the most recent era of 2012 to June 2013, only 2.6% received a BiVAD. Thus, this prejudice of utilizing LVAD-alone solutions for chronic heart failure and most importantly acute heart failure with shock is real but may be short-sighted. Takeda et al also provide some very critical insights into the condition of the RV after support with an unplanned RVAD. Although the patients who were weaned met good hemodynamic criteria for weaning, nearly 50% continued to have tricuspid insufficiency and severely compromised RV wall motion abnormalities 1 month after RVAD removal.
135
Multiple studies have identified clinical, hemodynamic and echocardiographic risk factors for the need for RV support after LVAD. However, as also seen in the study by Takeda and colleagues, the majority have been examined only within the context of their relevance to peri-operative outcome. Their study further provides valuable insight into the limitations of unplanned RVAD use, even when applied by a very experienced team using carefully adopted protocols of utilization. Little information exists regarding predictors for chronic RV dysfunction on LVADs. It is no longer about just getting the patient out of the operating room without an RVAD. What is desperately needed is a more detailed look at the long-term functional status of those patients supported with not only temporary RVADs but also those who require more extended support with long-term inotropic therapy even after hospital discharge. Only then will we truly understand the implications of utilizing LVAD therapy alone in the clinical scenario of moderately severe biventricular failure. My contention remains that technology development for biventricular failure is lagging and is thus poorly adopted. Our hope is that biventricular support may become more attractive with the introduction of smaller rotary blood pumps. These new technologies must be accompanied by a renewed focus on the peripheral and wearable components that balance the flow between the ventricles. Otherwise, we will rely on the centuries-old wisdom of Hippocrates who well understood the consequences of waiting too long in an illness and intervening when it reaches its crisis stage. Of course, in his wisdom he recognized the unpredictability of outcome in salvage surgery. But we should not let our treatments be dictated by anecdotes of success.
Disclosure statement The author has no conflicts of interest to disclose.
References 1. Kirklin JK, Naftel DC, Pagani FD, et al. Long-term mechanical circulatory support (destination therapy): on track to compete with heart transplantation? J Thorac Cardiovasc Surg 2012;144:584-603. 2. Takeda K, Naka Y, Yang JA, et al. Outcome of unplanned right ventricular assist device support for severe right heart failure after implantable left ventricular assist device insertion. J Heart Lung Transplant 2014;33:141-8. 3. Kormos RL, Teuteberg JJ, Pagani FD, et al. Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: incidence, risk factors, and effect on outcomes. J Thorac Cardiovasc Surg 2010;139:1316-24. 4. Naftel DC, Bittman RM, Pagani FD, et al. Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation. Circulation 2012;125:3191-200. 5. Kirklin JK, Naftel DC, Kormos RL, et al. Fifth INTERMACS annual report: risk factor analysis from more than 6,000 mechanical circulatory support patients. J Heart Lung Transplant 2013;32:141-56.
EDITORIAL COMMENTARIES
The right heart failure dilemma in the era of left ventricular assist devices Robert L. Kormos, MD From the Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
“In acute diseases it is not quite safe to prognosticate either death or recovery.” “If an operation is considered necessary, one should act at the beginning. “Once the illness has reached a peak, it is best left alone.”—Hippocrates: Aphorisms The challenges presented to clinicians by the failing right ventricle (RV) precede our most recent experiences with left ventricular assist devices (LVADs) by decades, yet for a multitude of reasons we seem not to have solved this difficult dilemma. The LVAD is both beneficial and detrimental to the RV. It is beneficial by reducing the RV’s work against pressure by decompressing the LV and thus the pulmonary capillary wedge pressure, which in turn passively reduces pulmonary vascular resistance. On the other hand, an LVAD, by decompressing the LV, can cause a leftward shift of the interventricular septum, which results in a more spherical shape to the RV, thus disadvantaging it in its mechanical contractile properties. In addition, a new set of hemodynamic conditions is presented to the RV. Whereas RV output had been equated to the LV output, once we have introduced an LVAD we raise the expected output of the RV to that of the LVAD. RV-developed pressure is determined by RV free wall function, LV function and interventricular septal position and function. Once the septum has been essentially disabled, the work becomes the responsibility of the anterior free wall of the RV. Thus, the anatomic, functional and physiologic parameters imposed upon the RV by an LVAD create a set of conditions whereby the RV operates in a disadvantaged mechanical zone, thus relying largely on a reduction in pulmonary after-load for its most of its operability. A delicate balance between adequate decompression and pump flow required for end-organ perfusion must be in place while protecting RV anatomic integrity. This produces what I refer to as the RV dilemma. Much of the early morbidity and mortality associated with LVADs relates to patient selection. INTERMACS clearly delineates the key effect of the selection of Level 1 patients upon peri-operative mortality and long-term outcome.1 Thus, although multiple parameters have evolved for assessing the
hemodynamic and echocardiographic risk factors for RV failure after LVAD use, many of these can be rendered less predictive by an overwhelming set of clinical conditions of acuity, pre-operative end-organ failure and cardiogenic shock, which ultimately translate into an inflammatory state that affects both RV contractility and pulmonary function. The role of the lung and its pathology and response to acute injury of surgery and shock has been under-recognized for its contribution to total pulmonary resistance, which can reduce the benefit that the LVAD provides in reducing the pulmonary after-load. We are therefore often driven to LVAD implantation in a subset of patients by the acuity of implantation. The percentage of patients presenting with acute cardiogenic shock is likely to grow as temporary percutaneous strategies of circulatory support become more widely applied in conditions of acute myocardial compromise and as centers become more comfortable with extracorporeal membrane oxygenation. In this issue of the journal, Takeda and colleagues report on their experience with the unplanned use of a right ventricular assist device (RVAD) in patients receiving a LVAD.2 Of 398 patients, 44 (11%) required a RVAD—over 64% of which were placed at the same operative setting and another 36% within 3 days of LVAD implantation. However, it is also important to note that another 9% of the total group had elective biventricular assist devices (BiVADs) implanted, thus revealing that 20% of the patients had a recognized or unrecognized risk for RV failure. Only 48% of the unplanned RVAD-supported patients could be weaned from their device. Again, in their study, as in others, the pre-implant clinical factors, such as level of end-organ failure, seemed to outweigh the more evidence-based rationale for selecting an LVAD alone according to echocardiographic or hemodynamic predictors. The early peri-operative outcomes also seem to support the strategy that a planned BiVAD implant has lower hospital mortality (30%) compared with use of an unplanned RVAD (50%). In many ways, Takeda et al confirm a prejudice that is rapidly growing in the mechanical support community. Many physicians have accepted RV failure as a necessary
1053-2498/$ - see front matter r 2014 International Society for Heart and Lung Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.healun.2013.12.019
Kormos
The Right Heart Failure Dilemma in the Era of Left Ventricular Assist Devices
evil of mechanical circulatory support and have grown to accept the morbidity and mortality associated with the needs for its use. This has led to the development of RVAD technologies that are based upon percutaneous solutions which may lead to earlier adoption of RVAD support. Clearly, the outcome of any of these solutions will have to be proven to be of benefit; currently, we are still faced with 50% mortality—and that merely addresses the population in whom RV failure was obvious due to the need for an RVAD. It does not address the larger population in whom inotropic support may be required for weeks to months after LVAD implantation. This subset of patients with RV dysfunction after LVAD may be over 2-fold larger than the subset requiring a RVAD.3,4 If we consider methods to reduce the risk of RV failure after LVAD implantation, the pre-operative optimization should then be focused on judicious inotropic support combined with efforts to reduce the loading conditions for the RV through aggressive diuresis and, if necessary, temporary use of an intra-aortic balloon pump. The goals are to improve end-organ perfusion to reduce the risk of multi-organ dysfunction, including pulmonary congestion, and to thereby optimize the RV. Intra-operatively, surgical techniques focus on proper pump positioning in the LV and avoidance of bleeding, hypotension, acidosis and volume overload. Overzealous product transfusion due to bleeding results in transfusion-related lung injury, which increases the total pulmonary resistance, again straining the RV. The maintenance of mean arterial pressure is critical for RV perfusion, but also prevents LV collapse due to overly aggressive LV unloading in the presence of low systemic after-load. Other medical strategies include ventilation, which reduces carbon dioxide while optimizing oxygen delivery. Reports of temporary right atrial to pulmonary artery bypass as an extension of the main cardiopulmonary bypass circuit while weaning from bypass have been shown to help gradually reintroduce the workload to the RV. It is critical to realize that clinicians are not enamored with using long-term BiVAD support or its alternative, the total artificial heart. The most recent INTERMACS5 data demonstrate that in 49,000 patients only 2% received a total artificial heart and another 5.7% received a BiVAD implant. It is even more telling that, before 2010, 11.8% of patients received a BiVAD and, in the most recent era of 2012 to June 2013, only 2.6% received a BiVAD. Thus, this prejudice of utilizing LVAD-alone solutions for chronic heart failure and most importantly acute heart failure with shock is real but may be short-sighted. Takeda et al also provide some very critical insights into the condition of the RV after support with an unplanned RVAD. Although the patients who were weaned met good hemodynamic criteria for weaning, nearly 50% continued to have tricuspid insufficiency and severely compromised RV wall motion abnormalities 1 month after RVAD removal.
135
Multiple studies have identified clinical, hemodynamic and echocardiographic risk factors for the need for RV support after LVAD. However, as also seen in the study by Takeda and colleagues, the majority have been examined only within the context of their relevance to peri-operative outcome. Their study further provides valuable insight into the limitations of unplanned RVAD use, even when applied by a very experienced team using carefully adopted protocols of utilization. Little information exists regarding predictors for chronic RV dysfunction on LVADs. It is no longer about just getting the patient out of the operating room without an RVAD. What is desperately needed is a more detailed look at the long-term functional status of those patients supported with not only temporary RVADs but also those who require more extended support with long-term inotropic therapy even after hospital discharge. Only then will we truly understand the implications of utilizing LVAD therapy alone in the clinical scenario of moderately severe biventricular failure. My contention remains that technology development for biventricular failure is lagging and is thus poorly adopted. Our hope is that biventricular support may become more attractive with the introduction of smaller rotary blood pumps. These new technologies must be accompanied by a renewed focus on the peripheral and wearable components that balance the flow between the ventricles. Otherwise, we will rely on the centuries-old wisdom of Hippocrates who well understood the consequences of waiting too long in an illness and intervening when it reaches its crisis stage. Of course, in his wisdom he recognized the unpredictability of outcome in salvage surgery. But we should not let our treatments be dictated by anecdotes of success.
Disclosure statement The author has no conflicts of interest to disclose.
References 1. Kirklin JK, Naftel DC, Pagani FD, et al. Long-term mechanical circulatory support (destination therapy): on track to compete with heart transplantation? J Thorac Cardiovasc Surg 2012;144:584-603. 2. Takeda K, Naka Y, Yang JA, et al. Outcome of unplanned right ventricular assist device support for severe right heart failure after implantable left ventricular assist device insertion. J Heart Lung Transplant 2014;33:141-8. 3. Kormos RL, Teuteberg JJ, Pagani FD, et al. Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: incidence, risk factors, and effect on outcomes. J Thorac Cardiovasc Surg 2010;139:1316-24. 4. Naftel DC, Bittman RM, Pagani FD, et al. Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation. Circulation 2012;125:3191-200. 5. Kirklin JK, Naftel DC, Kormos RL, et al. Fifth INTERMACS annual report: risk factor analysis from more than 6,000 mechanical circulatory support patients. J Heart Lung Transplant 2013;32:141-56.
