Selection Committee Member: Nisha Bansal @NishaKidneyDoc
Nisha Bansal is an Associate Professor and the Arthur Stach Family Endowed Professor in the Division of Nephrology at the University of Washington (UW). She is also an investigator in the Kidney Research Institute, the Associate Fellowship Program Director and the Director of the Kidney-Heart Service at UW. She is an expert in the pathophysiology, diagnosis and treatment of hypertension and cardiovascular disease in patients with chronic kidney disease and those treated with dialysis.
Writer: Jen Bergeron @DrJennyBee
Jen Bergeron is a chief and second-year nephrology fellow at Vanderbilt University. She is a graduate of Tufts University School of Medicine- Maine Track and completed her residency at the University of Vermont. Her clinical and research interests include palliative nephrology and ESRD care, sharing her love of renal physiology, and mentorship.
Writer: Jefferson Triozzi @nepherson
Jefferson L. Triozzi is a nephrology fellow at Vanderbilt University Medical Center where he also serves as a chief fellow. He now pursues a Master’s of Science in Clinical Investigation at Vanderbilt University School of Medicine. His interests are CKD and cardiometabolic diseases.
Competitors for the Heart Failure Devices Region
Amidst the political and cultural upheaval of the 1960s, a new era began in medicine—that of heart failure devices. In 1963, Dr. Michael E. DeBakey and colleagues successfully implanted an air-powered pump into the heart of a 37-year-old woman, allowing her to survive cardiogenic shock after open-heart surgery. We’ve come a long way since then, with the emergence of numerous cardiac devices indicated for acute and chronic settings (Table 1). Many technical advancements have been made in the last decade alone. Non-durable cardiac devices provide temporary support for the heart and restore systemic hemodynamics, such as those used during high-risk cardiac interventions or cardiogenic shock. Durable devices offer longer-term options and can serve as a bridge to transplantation or destination therapy. There are a number of factors a nephrologist must consider when caring for patients with a cardiac device. It’s no secret—heart, and kidney function are intricately linked, as we saw in the NephMadness 2022 Cardiorenal Region. Cardiac devices can offer benefits to patients with kidney disease, while simultaneously presenting challenges to the care of our patients.
Team 1: Cardiac Devices in AKI
Acute kidney injury (AKI) is a common complication in patients with advanced heart failure and often leads to long-term kidney dysfunction. In theory, a device that improves cardiac output and kidney perfusion should reduce the risk of AKI. But the story is not so straightforward.
Non-durable devices may reduce the risk of AKI in specific settings
Cardiac devices used in acute settings include the intra-aortic balloon pump, percutaneous ventricular assist devices (Impella, TandemHeart), and extracorporeal membrane oxygenation (ECMO) machines (Image 1).
Observational data suggests the Impella System lowers the risk of AKI in cardiogenic shock or high-risk cardiovascular interventions. In a case-control study, Impella use during high-risk percutaneous coronary intervention was associated with a lower risk of AKI (adjusted odds ratio = 0.13; 95% confidence intervals = 0.09–0.31, P<0.001) (see Visual Abstract 1 below). In a separate single-center study of patients with all-cause cardiac shock, the subset of patients with AKI demonstrated a significant decrease in serum creatinine with Impella-supported cardiac catheterization. Although these findings are hypothesis-generating and subject to confounding factors, several nephroprotective mechanisms have been proposed. One explanation is that devices maintain continuous kidney blood flow, thereby reducing ischemic tubular necrosis and ensuring an adequate glomerular filtration rate to prevent accumulation of contrast agents. A study in swine found a link between left ventricular unloading and a reduction in the proinflammatory cardiorenal response by placing this device prior to reperfusion in the setting of an acute myocardial infarction. Either way, supporting cardiac output could limit kidney damage when hemodynamics are compromised, at least in the short term.
AKI reversal after durable device placement
LVAD (left ventricular assist device) placement may initially lead to improved kidney function after placement. In a single-center observational study of 131 patients, kidney function improved in 75% of patients within the first month after LVAD placement (Visual Abstract 1). A multivariate analysis found that early AKI reversal was more likely among younger patients with lower baseline kidney function. Reversibility of AKI suggests impaired hemodynamics rather than intrinsic kidney damage as the main driver of kidney injury. Thus, lower baseline kidney function could represent greater potential for improvement due to the relief of venous congestion and the optimization of cardiac output that an LVAD provides. Cardiac devices may even help patients with reversible AKI to wean off of dialysis. In a small cohort of 68 LVAD patients, 5 out of 6 patients on dialysis pre-operatively recovered their kidney function within one month after LVAD placement. One of these patients was able to discontinue dialysis immediately after LVAD placement. The results of a separate meta-analysis examining AKI patients needing dialysis suggested that one-half will recover kidney function (defined as independence from dialysis within two weeks of injury) after the placement of an LVAD.
The data above suggest that younger patients and those with reversible, hemodynamic forms of AKI have potentially excellent short-term kidney outcomes after durable cardiac device placement. But what happens months and years down the line? Multi-center observational data demonstrates an interesting pattern of change in eGFR over two years after LVAD placement (Image 2). Kidney function improves at first but then declines. Why would this happen?
Durable devices can reverse AKI, but not for long…
For patients with advanced heart failure refractory to medical interventions, cardiac devices may be needed for the long haul. Ultimately, heart transplantation is the only curative therapy. Originally designed as a temporary “bridge” for those waiting for transplants, LVADs have evolved to become an essential long-term treatment option for patients ineligible for transplantation. The technology behind these devices has improved drastically—they have become smaller and more efficient (Image 3), allowing patients to live active lifestyles while receiving aid from the device. Additionally, LVADs can assist in cardiac recovery, providing hope to those suffering from heart failure.
There are many factors that ultimately lead to a decline in kidney function after cardiac device placement. The risk of AKI after LVAD placement is estimated between 5.1 to 33.3%. Not unexpectedly, those who develop AKI after device placement have decreased survival. There are many factors that could contribute to AKI, including perioperative factors, hemodynamic changes, vascular injury and non-pulsatile flow, hemolysis, and other much rarer tubular and glomerular pathologies.
We also note the challenges in measuring and monitoring kidney function in patients with advanced heart failure. Traditional creatinine-based formulas may not be accurate due to reduced muscle mass and creatinine production in these patients. Alternative markers, such as cystatin-C and NGAL, have modest success in this patient population. Ongoing research is seeking to better understand the unique challenges of kidney function assessment in the setting of advanced heart failure disease and to develop more reliable methods for measurement.
Perioperative & Hemodynamic Factors
Placing an LVAD is no walk in the park. LVAD implantation remains a high-risk surgery, with life-threatening complications potentially occurring in the perioperative phase. The use of cardiopulmonary bypass during LVAD placement increases the risk of AKI by triggering systemic inflammation, impairing vasomotor tone, and potentially creating microemboli in the renal capillaries. Excessive bleeding during surgery or the need for surgical revision could also contribute.
The tenuous hemodynamic status of patients with cardiac devices further predisposes patients towards AKI. Patients with an LVAD can develop right ventricular dysfunction, which may lead to kidney venous congestion and nephrosarca. It is estimated that 20%-50% of LVAD implantations are complicated by right heart failure (RHF). Therefore, RHF preventative strategies focus on managing the preload and afterload of the right ventricle and using vasodilators to reduce pulmonary vascular resistance. In extreme cases, surgery to also implant an RVAD (right ventricular assist device) may be necessary. However, RVAD placement in the setting of clinically severe right heart failure is often unsuccessful, leading some to advocate for RVAD placement much earlier.
While early LVAD iterations attempted to mimic the pulsing action of a healthy heart, subsequent devices using continuous flow demonstrated superior patient outcomes and device durability. However, novel studies suggest the continuous blood flow generated by the LVAD may harm the kidneys over time. In a calf animal model, investigators showed that reduced pulsatility produced severe periarteritis in the kidneys (make sure to check out the pathology pictures in this article), which was associated with an upregulation of the local renin-angiotensin system and inflammation. Other vascular changes, such as increased stiffness of the aorta, may be related to non-pulsatile blood flow.
Hemolysis is common in cardiac devices due to the level of shear stress on red blood cells. Additionally, turbulent blood flow, such as from clot formation in the LVAD pump or inadequate pump speed settings, exacerbates damage to red blood cells. Hemolysis, whether overt or subclinical, can lead to worsening kidney function in several ways. Pigment nephropathy due to LVAD-related hemolysis has been reported. Recently, investigators have identified a proximal tubulopathy related to chronic hemolysis in LVAD patients. The authors identified LVAD patients with proteinuria, glycosuria, and potassium and phosphorus wasting. The authors speculated that the mechanism of proximal tubulopathy was due to LVAD-related hemolysis, similar to the Fanconi-type syndrome seen in hemolytic conditions like sickle cell disease or paroxysmal nocturnal hemoglobinuria. In addition to increasing the risk of AKI, hemolysis is associated with both increased risk for cerebrovascular accident and death. Therefore, some centers routinely monitor plasma-free hemoglobin to proactively detect hemolysis and prevent complications, though it is unclear if this practice improves outcomes. When hemolysis is identified, echocardiography can help to identify mispositioning that may be causing obstruction to the device’s inlet or outlet. In cases where hemolysis is accompanied by a drop in effective blood volume, blood transfusions or volume expansion may also be necessary.
Lastly, development of glomerulonephritis has been described in a case series of patients with LVAD. The authors describe a rare form of “LVAD vasculitis” which presents with infection, skin rash, and AKI. Kidney biopsies of these patients demonstrated infection-associated glomerulonephritis (Image 4). Of note, drive-line infections are the most common non-surgical complication after implantation.
Newer iterations of ventricular assist devices using different flow techniques may prove beneficial for patient outcomes. There have been notable changes in technologies, including a shift from axial to centrifugal flow (Image 5). The landmark REMATCH trial brought axial flow technology to the masses in 2001. Axial flow pumps work by a propeller in a pipe screwing itself into the incoming blood and pushing it towards the outlet. More recently, the MOMENTUM 3 trial showed that a novel magnetically levitated centrifugal continuous-flow LVAD (HeartMate3) had better outcomes than axial pumps. Centrifugal flow pumps more gently capture incoming blood in a centrifuge and sweep it tangentially off the blade tips into the outlet pipe. 77% of patients who received the centrifugal LVAD remained alive and free of disabling stroke or reoperation to replace/remove a malfunctioning device at two years compared to 65% of patients with axial LVADs (relative risk 0.84, 95% confidence intervals = 0.78–0.91). Centrifugal flow pumps had improved hemocompatibility which decreased the occurrence of de novo pump thrombosis, ischemic and hemorrhagic strokes, and nonsurgical bleeding. The HeartMate3 introduced another interesting feature—an artificial pulse created by alternating the speed of the pump every two seconds. Whether this technology will positively impact kidney outcomes is unclear. Regardless, HeartMate3 has largely replaced previous models in practice.
Patient Selection and Prognosis
As discussed above, LVAD implantation is a complicated procedure with high morbidity and mortality. Real-world data after Momentum 3 showed that 5-year survival was 59% in the centrifugal-flow pump group and 44% in the axial-flow pump group (p=0.003), suggesting that newer LVADs might have a slight survival benefit, though overall outcomes are still poor. The HeartMate 3 Risk Score was validated to predict mortality after LVAD placement. Not surprisingly, kidney biomarkers (identified by serum sodium and BUN) are the strongest predictors. Whereas younger patients with reversible AKI may have lower risks, older patients with baseline chronic kidney disease may have higher risks. Traditionally, baseline eGFR < 30 mL/min was a relative contraindication to LVAD placement, but as device placement has become increasingly commonplace there are more patients with more advanced kidney disease who qualify for a device. Optimizing nephrology care before and after surgery is vital to improve outcomes.
Check out this podcast episode of Cardionerds featuring Brian Houston and Nisha Bansal:
Team 2: Cardiac Devices in ESKD
The number of patients with LVADs who require long-term dialysis is on the rise. The risk of requiring kidney replacement therapy after LVAD placement ranges from 9.0% to 38.1%. This is mostly due to the high prevalence of chronic kidney disease in heart failure patients and the risk of irreversible AKI after device implantation. And although “irreversible kidney disease” is listed as a contraindication for device placement per the American College of Cardiology, we are starting to see small but growing numbers of LVAD placements in patients with end-stage kidney disease (ESKD).
Outcomes are poor—how can we improve them?
Outcomes for patients with LVADs are tracked by two large registries: INTERMACS (US patients with FDA-approved devices) and EUROMACS (European registry for patients with mechanical circulatory support devices). The data are clear: Patients with LVADs who require kidney replacement therapies have poor outcomes. Early studies revealed 30% mortality within 3 months for patients with ESKD after LVAD implantation. In one study of Medicare claims and USRDS data that included 155 patients with ESKD, patients with ESKD and an LVAD survived a median of 16 days compared to a median of 2,125 days for patients with an LVAD but without ESKD (Visual Abstract 3). How can we improve these outcomes and support patients until transplant?
Patients with LVADs can safely receive hemodialysis but face unique challenges. One important issue is that most outpatient dialysis units do not admit LVAD patients as part of their patient population, due in large part to uncertainty around dialysis staff’s technical expertise. Nevertheless, some dialysis centers have developed structured programs to successfully provide dialysis care for LVAD patients. In a retrospective case series of LVAD patients requiring outpatient hemodialysis, most patients survived to transplantation or kidney recovery (Image 6). This study reported that dialysis was well-tolerated (~90% of dialysis sessions free of symptoms) with low dialysis-related adverse events (~5% of treatments with symptomatic hypotension). Below, we will review some considerations related to hemodynamics and blood pressure, vascular access, infection risk, and anemia management that are unique to LVAD patients requiring outpatient hemodialysis.
Hemodynamics and Blood Pressure
Continuous flow devices do not generate a palpable thrill or bruit…or pulse, for that matter! Point-of-care ultrasound can be used to assess flow, and ultrasound/doppler-guided blood pressure techniques are also possible. Patients with cardiac devices may be more sensitive to hemodynamic shifts that occur related to intermittent dialysis. Nursing and staff must be trained to understand the LVAD settings to ensure safe limits are maintained for parameters (including the pump speed, flow, and pulsatility index) which are affected by changes in preload and afterload.
Fistulas are a safe and effective way to provide dialysis access in patients with LVADs. It was previously thought that the non-pulsatile blood flow of continuous flow devices would impair fistula maturation, but this did not turn out to be the case in several reports. In 2020, a case series showed that arteriovenous grafts were also safe in patients with LVADs (Image 8). Moreover, HD central venous catheters have a significantly increased risk of developing bacteremia. The presence of a catheter and an intravascular device puts these individuals at especially high risk for infection. Alternative options such as arteriovenous fistulas or arteriovenous grafts could provide safer and more efficient means of access than catheters (Image 7).
Risk of Infection
We know that patients requiring long-term renal replacement therapies are vulnerable to infections, often related to vascular access. Infections remain the most common complication of LVAD devices, too. These include infective endocarditis, bloodstream infections, mediastinitis, and contamination of the soft tissue at or near the site of cardiac device implantation. Driveline infections are the most common cause. The driveline connects the LVAD controller and batteries, which remain outside of the body, to the internal thoracic pump. The driveline is tunneled in the subcutaneous space, providing a focus of entry for microbes to colonize the device and form biofilms. Management of such driveline infections includes 2-4 weeks of targeted antimicrobial therapy, but severe or refractory cases may require chronic suppressive antibiotics or driveline exchange for source control. The risk of infection from vascular access and drivelines combined represents a considerable morbidity and mortality in these patients.
Patients requiring both dialysis and a heart failure device have a compounding risk for severe anemia (related to anemia of chronic disease), gastrointestinal bleeding due to anticoagulant requirements, and hemolysis (explored above). In addition, both dialysis and heart failure devices raise challenges related to managing anemia. Blood transfusions come with the risk of sensitization prior to solid organ transplantation. And while the use of erythropoiesis-stimulating agents (ESAs) with LVAD can help address low red blood cell levels, the thrombosis risk may be heightened for patients with cardiac devices (Visual Abstract 4). A retrospective study identified increased pump thrombosis in LVAD patients receiving ESAs. This finding was dose-responsive and even found that the use of ESAs was associated with a higher rate of all-cause mortality (HR 1.62). Although these data are subject to residual confounders, it is something we should be cautious about.
Peritoneal dialysis (PD) was traditionally contraindicated for patients with LVADs because the driveline disrupted the peritoneal membrane. Newer devices leave the peritoneal cavity intact, allowing for safe PD. PD may offer several potential benefits for patients with LVADs, including gentle ultrafiltration and a lower risk of catheter-related infections. PD may also preserve residual kidney function which has been shown in several studies to impact survival and patient quality of life. Given the frequent vascular interventions that LVAD patients often undergo, finding adequate anatomy for creating an arteriovenous fistula or graft may not be feasible—making PD a great option. Additionally, PD allows for the possibility of providing dialysis care at home, which can be particularly advantageous since many outpatient facilities may not have experience safely dialyzing LVAD patients (as above).
Outpatient dialysis care for patients living with heart failure devices poses unique practical challenges. It is also of utmost importance that nephrologists work closely with advanced heart failure physicians to make sure all available treatment options are discussed and weighed for each patient. Many patients, such as those in rural areas, may not have easy access to centers providing this highly specialized care. Furthermore, the existing dialysis centers rural patients have access to likely do not have staff with the special training to adequately care for patients with heart failure devices. Education and training programs for dialysis staff on working with patients with LVADs is required. The emphasis on home dialysis modalities, including PD and home hemodialysis (HHD), have been successful in circumventing these hurdles. Novel approaches using telemonitoring could prove beneficial by expanding access and monitoring for these patients.
The use of advanced cardiac devices, much like that of dialysis, has raised several ethical questions since its creation. These issues are magnified when patients require not one, but two forms of life-support for the heart and kidneys. Care teams must weigh the risks and benefits of life-sustaining modalities in terms of beneficence/non-maleficence, futility, and respect for patients’ autonomy in deciding if this new condition is acceptable to them or not. Deactivation of LVADs, much like discontinuation of dialysis, is an ethical quagmire. Health and legal systems worldwide vary on end-of-life care for patients with devices, with nuances between “allowing a patient to die” and physician-assisted suicide. There are many other unanswered questions. For example, if a dialysis patient is receiving a cardiac device as a bridge to transplantation, but then develops a contraindication for transplantation, should terminal deactivation of the cardiac device be discussed? When is the treatment considered futile? What if the patient asks for deactivation? How do we best evaluate patients with dual organ failure for transplantation? Both dialysis and cardiac devices are costly—should we factor in societal justice into the care of these patients?
Shared decision-making with nephrologists, cardiologists, transplant teams, and our patients is important when considering the appropriateness of cardiac devices for patients with ESKD. Although irreversible kidney failure is a contraindication for device placement, perhaps some dialysis patients would indeed benefit from device placement, such as those likely to survive until transplantation. In one study, the median time to death after LVAD placement in ESKD was an abysmal 16 days, with very few making it alive long enough to transplant. A closer look at the data reveals that the interquartile range of survival spans up to 447 days. Identifying the subset of patients with ESKD in which device placement may prolong life in a meaningful way is critical to promoting their care.
The use of cardiac devices has grown rapidly in recent years, with many areas needing improved care that nephrologists can provide. As we discuss the role of cardiac devices in AKI and ESKD, there are a few key points to consider. On one hand, we have the potential benefits—using short-term devices during cardiogenic shock or high-risk interventions, or long-term devices as a bridge to transplantation or destination therapy. On the other hand, we must consider the increased risks of complications, including death, especially for patients with advanced kidney disease or those requiring chronic dialysis. Caring for these patients presents challenges related to complex hemodynamic needs. It can be tricky to navigate, but ultimately teamwork and collaboration are key in ensuring that cardiac devices are used effectively.