Clinical and economic impact of ventricular assist device infections: a real-world claims analysis.

BACKGROUND: VAD therapy has revolutionized the treatment of end-stage heart failure, but infections remain an important complication. The objective of this study was to characterize the clinical and economic impacts of VAD-specific infections. METHODS: A retrospective analysis of a United States claims database identified members ≥ 18 years with a claim for a VAD implant procedure, at least 6 months of pre-implant baseline data, and 12 months of follow-up between 1 June 2016 and 31 December 2019. Cumulative incidence of infection was calculated. Infection and non-infection cohorts were compared regarding mortality, healthcare utilization, and total cost. Regression models were used to identify risk factors associated with infections and mortality. RESULTS: A total of 2,259 patients with a VAD implant were included, with 369 experiencing infection (12-month cumulative incidence 16.1%). Patients with infection were 2.1 times more likely to die (p < 0.001, 95% CI [1.5-2.9]). The mean 12-month total cost per US patient was $354,339 for the non-infection cohort and $397,546 for the infection cohort, a difference of $43,207 (p < 0.0001). CONCLUSIONS: VAD infections were associated with higher mortality, more healthcare utilization, and higher total cost. Strategies to minimize VAD-specific infections could lead to improved clinical and economic outcomes.

The Jarvik 2000 Left Ventricular Assist Device: Results of the United States Bridge to Transplant Trial.

The Jarvik 2000 bridge to transplant investigational device exemption study was a multicentered, prospective study of 150 UNOS status I patients implanted with the Jarvik 2000 between 2005 and 2012. During the study period, there were numerous modifications of the system that included converting from pin to cone bearings. Results were analyzed for three cohorts: total (n = 150), pin (n = 128), and cone (n = 22). Baseline demographics included age (52 ± 13), gender (79% male), size (BSA 1.98), and etiology (37% idiopathic dilated cardiomyopathy; 43% Ischemic). Seventy percent of patients were either INTERMACS 1 or 2. The primary endpoint-defined as successful transplantation or listing at 180 days (prespecified at 65%; 95% lower CI: 57%)-was successfully achieved for the total cohort (67.3%; 95% CI: 59.5%-74.3%; p = 0.006). In subgroup analysis of the more contemporary, cone-bearing group, the primary endpoint was met in 91% (95% CI: 72%-97.5%; p = 0.001). Compared with pin patients, cone-bearing patients had less hemolysis as well as decreased end-organ dysfunction. Functional and quality of life scores improved after implantation independent type of bearing. In conclusion, despite a particularly sick patient population, the Jarvik 2000 was shown to be effective in supporting the advanced HF patient.

Global best practices consensus: Long-term management of patients with hybrid centrifugal flow left ventricular assist device support.

OBJECTIVES: Six months after withdrawal of the HeartWare HVAD System (HVAD; Medtronic) from sale, approximately 4000 patients continue ongoing support with this device. In light of the diminishing experience, this global consensus document summarizes key management recommendations. METHODS: International experts with experience in the management of patients with ongoing HVAD support were invited to summarize key aspects of patient and pump management and highlight differences in the current HeartMate 3 (Abbott Laboratories) ventricular assist device. Clinicians from high-implanting HVAD sites reviewed current literature and reported experience to generate a consensus statement. RESULTS: Specific guidelines to assist in the management of ongoing HVAD patients are developed. Key management protocols and helpful techniques developed from experienced clinicians are combined into a short guideline document. As experience with HeartMate 3 increases, key differences in approach to management are highlighted, where appropriate. CONCLUSIONS: With decreasing worldwide experience in the ongoing management of HVAD-supported patients, this consensus guideline provides a summary of best practice techniques from international centers. Differences in HeartMate 3 management are highlighted.

Higher levels of allograft injury in black patients early after heart transplantation.

Black patients suffer higher rates of antibody-mediated rejection and have worse long-term graft survival after heart transplantation. Donor-derived cell free DNA (ddcfDNA) is released into the blood following allograft injury. This study analyzed %ddcfDNA in 63 heart transplant recipients categorized by Black and non-Black race, during the first 200 days after transplant. Immediately after transplant, %ddcfDNA was higher for Black patients (mean [SE]: 8.3% [1.3%] vs 3.2% [1.2%], p = 0.001). In the first week post-transplant, the rate of decay in %ddcfDNA was similar (0.7% [0.68] vs 0.7% [0.11], p = 0.78), and values declined in both groups to a comparable plateau at 7 days post-transplant (0.46% [0.03] vs 0.45% [0.04], p = 0.78). The proportion of Black patients experiencing AMR was higher than non-Black patients (21% vs 9% [hazard ratio of 2.61 [95% confidence interval: 0.651-10.43], p = 0.18). Black patients were more likely to receive a race mismatched organ than non-Black patients (69% vs 35%, p = 0.01), which may explain the higher levels of early allograft injury.

Time in Therapeutic Range Significantly Impacts Survival and Adverse Events in Destination Therapy Patients.

The study aim was to examine the impact time in therapeutic range (TTR, International Normalized Ratio [INR] 2.0-3.0) has on survival and adverse events in patients receiving the HeartWare HVAD System in the ENDURANCE and ENDURANCE Supplemental Trials. Evaluable subjects (n = 495) had >1 INR value recorded 1-24 months postimplant and were categorized as: low TTR (10-39%), moderate TTR (40-69%), and high TTR (≥70%). Baseline characteristics, adverse events, and survival were analyzed. Low TTR patients experienced higher rates of major bleeding (1.69 vs. 0.54 events per patient year [EPPY]; p < 0.001), GI bleeding (1.22 vs. 0.38 EPPY; p < 0.001), stroke (0.47 vs. 0.17 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.02), infection (1.44 vs. 0.69 EPPY; p < 0.001), and renal dysfunction (0.23 vs. 0.05 EPPY; p < 0.001) compared with high TTR. Moderate TTR had higher rates of major bleeding (0.75 vs. 0.54 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.007), cardiac arrhythmia (0.32 vs. 0.24 EPPY; p = 0.04), and infection (0.90 vs. 0.69 EPPY; p = 0.001) compared with high TTR. Two year survival was greater among moderate and high versus low cohorts (Log-rank p = 0.001). The significant reduction in morbidity and mortality in destination therapy (DT) HVAD patients with well-controlled TTR (≥70%) emphasizes the importance of vigilant anticoagulation management.

Comparison of two individualized antithrombotic protocols in HeartWare HVAD recipients.

We previously reported low rates of pump thrombosis and hemorrhagic stroke, but increased bleeding, under our original antithrombosis protocol (P1) in HeartWare recipients. We designed and implemented a revised protocol (P2) to reduce complexity and bleeding. Thrombelastography and PFA-100 guide antiplatelet titration. Goals for P2 were altered to decrease antiplatelet use and anticoagulation intensity. We compared the incidence and rates of gastrointestinal bleeding (GIB), embolic (eCVA) and hemorrhagic (hCVA) stroke, pump thrombosis (PT), and total bleeding (GIB+hCVA), total thrombosis (eCVA+PT), and total events between P1 and P2. Laboratory and medication data were assessed. Patients with and without hemocompatibility-related adverse events (HRAEs) were compared. The study included 123 patients (P1: 65; P2: 58). GIB rate decreased (P1: 0.66; P2 0.30 EPPY, P = .003). CVA rates and incidence were statistically similar, although hCVA incidence increased (P1: 3%; P2: 12%, P = .06). Incidence (P1: 3%; P2: 16%, P = .02) and rate (P1: 0.03; P2: 0.12 EPPY, P = .08) of PT increased. Incidence and rate of overall HRAEs and thrombotic events were similar, while bleeding rate decreased (P1: 0.69; P2: 0.40 EPPY, P = .02). Twelve-month medication burden decreased. Compared to non-HRAE patients, patients with bleeding HRAEs had more antiplatelet and pentoxifylline use, but less statin use; and lower PFAs. Patients with thrombotic HRAEs had less dual antiplatelet use, lower INRs, R-times, and PFA-ADP values. A revised antithrombotic protocol decreased GIB and overall hemorrhagic HRAE rate and medication burden. Unfortunately, PT increased. Non-HRAE and HRAE patients differed in anticoagulation and antiplatelet intensity. These differences will guide the revision of P2.

Minimally Invasive Left Ventricular Assist Device Insertion Facilitates Subsequent Heart Transplant.

OBJECTIVE: We have observed that minimally invasive left ventricular assist device (LVAD) insertion leads to more facile re-entry and easier cardiac transplantation. We hypothesize minimally invasive LVAD implantation results in improved outcomes at the time of subsequent heart transplant. METHODS: All adults undergoing cardiac transplantation between October 2015 and March 2019 at our institution were retrospectively reviewed. Those bridged to transplantation with a HeartWare HVAD were identified and divided into 2 cohorts based upon the surgical approach: those who underwent HVAD placement by conventional sternotomy versus minimally invasive insertion via lateral thoracotomy and hemisternotomy (LTHS). Patient demographics, as well as perioperative transplant outcomes, including survival, length of stay (LOS), blood utilization, ischemic time, bypass time, and postoperative extracorporeal membrane oxygenation (ECMO) were compared between cohorts. RESULTS: Forty-two patients were bridged to heart transplant with a HVAD implanted via either sternotomy (n = 22) or LTHS technique (n = 20). Demographics were similar between groups. There was 1 predischarge death in the sternotomy group and none in the LTHS group. Body surface area, cardiopulmonary bypass time, ischemic time, ECMO utilization, and reoperation for bleeding were similar. Red blood cell units transfused were significantly lower in the LTHS cohort (3.0 [1.0-5.0] vs 6.0 [2.5-10.0] P = 0.046). The LTHS cohort had a significantly shorter hospital LOS (12.0 [11.0-28.0] vs 22.5 [15.7-41.7] P = 0.022) with a trend toward shorter intensive care unit LOS (6.0 [5.0-10.5] vs 11.0 [6.0-21.5] days P = 0.057). CONCLUSIONS: Minimally invasive HVAD implantation improves outcomes at subsequent heart transplantation, resulting in shorter LOS and less red cell transfusion. Larger multi-institutional studies are necessary to validate these findings.

A Minimally Invasive Approach to Left Ventricular Assist Device Insertion Facilitates Subsequent Explant.

A minimally invasive approach to left ventricular assist device (LVAD) insertion may benefit patients at the time of implant, but whether the approach to LVAD insertion influences the outcome of subsequent cardiovascular reoperations is unknown. Here we present the case of a 50-year-old male who underwent LVAD insertion through a minimally invasive approach and subsequently had left ventricular recovery. LVAD explant was performed without the use of any blood products or inotropic support. This case demonstrates that a minimally invasive approach to LVAD insertion may also facilitate subsequent device explant.

Outcomes with temporary mechanical circulatory support before minimally invasive centrifugal left ventricular assist device.

BACKGROUND: Despite improved survival and morbidity after durable left ventricular assist device (dLVAD), outcomes for cardiogenic shock patients are suboptimal. Temporary mechanical circulatory support (tMCS) can permit optimization before dLVAD. Excellent outcomes have been observed using minimally-invasive dLVAD implantation. However, some feel tMCS contraindicates this approach. To evaluate whether left thoracotomy/hemisternotomy (LTHS) dLVAD placement is safe in this setting, we compared patients who did and did not require tMCS. METHODS: Outcomes for patients receiving dLVADs via LTHS were compared among those bridged with extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), or no tMCS. We evaluated demographics, comorbidities, laboratory and hemodynamic data, and intraoperative and postoperative outcomes. RESULTS: Eighty-three patients underwent LTHS dLVAD placement. Fifty did not require tMCS, while 22 (26%) required IABP, and 11 (13%) ECMO. Non-tMCS patients were primarily Intermacs 3 (56%), while IABP recipients were mainly Intermacs 2 (45%). All patients with ECMO were Intermacs 1. Patients with tMCS had worse end-organ function. Operative outcomes were similar except more concomitant procedures and red-cell transfusions in patients with ECMO. Intensive care unit and hospital length of stay and inotrope duration were also similar. There were no differences in bleeding, stroke, and infection rates. Three- and 12-month survival were: no tMCS: 94%, 86%; IABP: 100%, 88%; and ECMO: 81%, 81% (P = .45). CONCLUSIONS: Patients with cardiogenic shock can safely undergo LTHS dLVAD implantation after stabilization with ECMO or IABP. Outcomes and complications in these patients were comparable to a less severely ill cohort without tMCS.

FDG PET/CT for Early Detection and Localization of Left Ventricular Assist Device Infection: Impact on Patient Management and Outcome.

OBJECTIVES: The feasibility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) for the diagnosis of left ventricular assist device (LVAD) infection has been demonstrated. Beyond the diagnoses of LVAD infection, the authors hypothesized that the pattern and site of the infection along its various components may significantly impact clinical management and patient outcome. BACKGROUND: In patients with end-stage heart failure, the clinical use of LVAD for destination therapy is on the rise, accompanied by a higher prevalence of infections and serious complications. METHODS: FDG PET/CT was performed in 35 heart failure patients with LVAD, 24 with and 11 without clinical suspicion of infection. Microbiology and/or clinical follow-up were used as the final diagnosis standard. Survival rates were compared in patients with and without FDG evidence of infection, and in relation to peripheral (exit wound site or driveline) versus central (cannula or pump) device infection. RESULTS: Of 35 patients, 28 (80%) showed metabolic evidence of LVAD infection: 5 limited to the periphery and 23 with extension to the central components of the device. The remaining 7 patients showed no metabolic evidence of infection, which was confirmed by microbiology and clinical follow-up. When CT images were interpreted independently from the FDG PET and clinical information, only 4 of 35 (11%) suggested the possibility of infection. Fourteen of 28 (50%) infected patients died during a mean of 23 months of follow-up after the diagnosis by FDG PET/CT: 12 (86%) with central infection and only 2 with peripheral infection. By contrast, none of the 7 (0%) noninfected patients died (p = 0.03). CONCLUSIONS: FDG PET/CT is a useful technique for identifying LVAD infection and determining the site and pattern of the infection. The latter has clinical management and patient outcome implications.

Individualized Antithrombotic Therapy in Heartware HVAD Recipients.

There are no evidence-based guidelines for antithrombotic therapy in left ventricular assist device patients. We evaluated the efficacy of a multi-agent, test-guided protocol, which remained consistent throughout our use of the Heartware HVAD. Thrombelastography and platelet function analyzer (PFA)-100 guide antiplatelet titration. Goals are normal kaolin thrombelastography maximum amplitude and prolonged PFA-100. We analyzed incidence and rates of nonprocedural bleeding, stroke, and pump thrombosis for all 81 primary Heartware left ventricular assist devices implanted since 2011. For each event, we examined whether each test was within goal range. We also compared medication burden and dosage between patients with and without events. Pump thrombosis and hemorrhagic stroke each occurred in two patients (2.5%; 0.03 events/patient-year [EPPY]), and ischemic stroke in six (7.4%; 0.10 EPPY). Nonprocedural bleeding occurred 75 times in 34 patients (42%; 1.24 EPPY), primarily gastrointestinal (28%; 0.66 EPPY). Subtherapeutic international normalized ratio (INR) was the most common at thrombotic events; supratherapeutic partial thromboplastin time, international normalized ratio (INR), and PFA-adenosine diphosphate (ADP) were common at bleeding events. Medication burden and dosage were lower in patients with events than in stable patients. Protocol-guided antithrombotic therapy resulted in low rates of pump thrombosis and hemorrhagic stroke. Ischemic stroke and gastrointestinal bleeding rates were higher than in a comparable HVAD population. Optimization of our protocol to decrease its complexity and to reduce bleeding is underway.

Quantitative Assessment of Inflow Malposition in Two Continuous-Flow Left Ventricular Assist Devices.

BACKGROUND: We previously investigated preoperative variables associated with qualitative inflow cannula malposition in the HeartMate II (Thoratec-Abbott, Abbott Park, IL) continuous-flow left ventricular assist device. In this report, we assess inflow cannula malposition quantitatively in recipients of both the HeartMate II and the HeartWare (Medtronic-HeartWare, Minneapolis, MN) and examine its association with device thrombosis. METHODS: Malposition was quantified based on angular deviation from a hypothetic ideal inflow cannula position in two orthogonal computed tomography imaging planes. Ideal position lies on a line from the apex to the center of the mitral valve. Positive anterior plane angulation indicates deviation toward the superior free wall; negative, toward the inferior wall. Positive lateral plane angulation indicates deviation toward the septum; negative, toward the lateral wall. Device thrombosis was assessed based on clinical criteria. RESULTS: Fifty-four HeartMate II patients and 68 HeartWare patients were analyzed. Inflow cannula deviation was significantly higher for HeartMate II than for HeartWare (anterior plane angle 36.7 ± 16.8 versus -18.7 ± 11.6 degrees, p < 0.001; lateral plane angle 23.7 ± 20.1 versus 0.2 ± 15.0 degrees, p < 0.001. Pump thrombosis occurred in 31% of HeartMate II patients and 2.9% of HeartWare patients (p < 0.001). In a multivariate model, HeartMate II and increasing inflow cannula deviation toward the septum were associated with higher thrombosis risk (odds ratio 1.35 per 10-degree increase). CONCLUSIONS: We found distinct device-dependent differences in inflow cannula positioning and thrombosis, with HeartWare showing both less malposition and less thrombosis. Malposition toward the ventricular septum may contribute to pump thrombosis through a vicious cycle of suction events, low flow, and speed reduction.

Systemic Inflammatory Response Syndrome After Contentious-Flow Left Ventricular Assist Device Implantation and Change in Platelet Mitochondrial Membrane Potential.

BACKGROUND: The objective of this study was to investigate the change of platelet function and platelet mitochondrial membrane potential in contentious-flow left ventricular assist device (CF-LVAD)-implanted heart failure (HF) patients with or without systemic inflammatory response syndrome (SIRS). METHODS AND RESULTS: We recruited 31 CF-LVAD patients (16 SIRS and 15 non-SIRS) and 11 healthy volunteers as control. Pre- and post-implantation blood samples were collected. We used PFA-100 to test platelet functionality. Mitochondrial potential-sensitive dye was used to detect platelet dysfunction (mitochondrial membrane potential; ΔΨm) via flow cytometry. The percentage of depolarized-ΔΨm platelets was found to be a preexisting condition in all HF patients before CF-LVAD implantation compared with control subjects (10.3 ± 6.3% vs 2.8 ± 2.2%; P < .001). As evident from the PFA-100 test, the HF patients who developed SIRS after CF-LVAD implantation had significantly more qualitative platelet defects and thrombocytopathies compared with baseline. After implantation, the depolarized platelets in the SIRS patients increased by 2-fold compared with baseline (18.2 ± 8.4% vs 9.0 ± 6.6%; P < .01); whereas no change was noticed in the non-SIRS patients (10.9 ± 6.2% vs 11.7 ± 5.8%; P = .75). CONCLUSIONS: We identified that platelet function and mitochondrial damage were enhanced in CF-LVAD patients with SIRS. Our findings suggest that depolarization of mitochondrial membrane potential is associated with SIRS after CF-LVAD implantation surgery.

Comparison of intraplatelet reactive oxygen species, mitochondrial damage, and platelet apoptosis after implantation of three continuous flow left ventricular assist devices: HeartMate II, Jarvik 2000, and HeartWare.

Differences in device design may have an effect on platelet damage and associated clinical complications. We aimed to compare device-specific platelet functionality in 26 heart failure patients supported with three continuous-flow left ventricular assist devices: HeartMate II (n = 8), Jarvik 2000 (n = 9), and HeartWare (n = 9). Intraplatelet reactive oxygen species (ROS) generation, mitochondrial damage, and platelet apoptosis were compared between device types before and after the implantation at every week up to 1 month. Overall, the baseline characteristics, demographics, routine laboratory values were comparable between the three device groups. Intraplatelet ROS, mitochondrial damage, and platelet apoptosis significantly elevated in the HeartWare group in comparison with the other two device groups after implantation. The major bleeding, infections, systemic inflammatory response syndrome, and right ventricular failure were found to be more common among the HeartWare group than others. Intraplatelet ROS and platelet damage levels were returned to baseline in both the HeartMate II and the Jarvik groups, whereas in HeartWare group they remained elevated. The patients with the Jarvik and the HeartMate II experienced less clinical complications and the platelet functionality is not compromised by these devices. Data from this study suggests that the continuous-flow left ventricular assist devices design may exert different effects on platelet function.

Intraplatelet reactive oxygen species, mitochondrial damage and platelet apoptosis augment non-surgical bleeding in heart failure patients supported by continuous-flow left ventricular assist device.

Non-surgical bleeding (NSB) is the most common clinical complication among heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). Understanding the role of platelet functionality contributing to NSB after CF-LVAD implantation is crucial for prevention and management of this adverse event. The aim of this study was to examine the role of intraplatelet reactive oxygen species (ROS) and platelet damage on the incidence of bleeding events after CF-LVAD implantation in HF patients. We recruited 25 HF patients implanted with CF-LVADs and 11 healthy volunteers as the control. Intraplatelet ROS generation, platelet mitochondrial damage and platelet apoptosis were quantified by flow cytometry. Among 25 patients, 8 patients developed non-surgical bleeding within one month after CF-LVAD implantation. Intraplatelet ROS, depolarized and apoptotic platelet were found to be pre-existing conditions in all baseline samples of the 25 HF patients when compared to the healthy volunteers. There was no significant difference in the levels of ROS between the non-bleeder and the bleeder groups prior to CF-LVAD implantation, although we noticed 2-fold and 1.5-fold rise in depolarized and apoptotic platelets, respectively, in the bleeder group compared to those in the non-bleeder group. Post implant levels of intraplatelet ROS, depolarized and apoptotic platelets increased and remained elevated in the bleeder group, whereas periodic decreases were noticed in the non-bleeder group, suggesting the potential role of platelet damage on bleeding incidence. ROS generation after CF-LVAD implantation positively associated with platelet apoptosis (ρ = 0.4263, p = 0.0023) and depolarized platelets (ρ = 0.4774, p = 0.0002), especially the latter. In conclusion, elevated intraplatelet ROS and platelet damage may be linked to the NSB among HF patients supported by CF-LVAD. These results provide mechanistic insights into the bleeding complication in patients with CF-LVAD support.

University of Maryland surgical experience with the Jarvik 2000 axial flow ventricular assist device.

BACKGROUND: The Jarvik 2000, an axial flow ventricular assist device (VAD), is currently under investigation for bridge to transplant (BTT) indications. The principal advantage of the Jarvik device is intraventricular pump placement. This eliminates the inflow cannula and pump pocket and allows for uncomplicated left ventricular implantation without sternotomy. Here we describe the evolution of our surgical implantation and explantation technique. METHODS: Data for all patients undergoing implantation of a left VAD (LVAD) (n=35) at the University of Maryland between September 2002 and September 2010 were retrospectively reviewed. Preoperative patient demographics and clinical status and operative technique and outcomes were reviewed. RESULTS: A simple technique for enclosing the pump and outflow graft greatly simplifies the explantation procedure and reduces the risk of lung adhesions and injury. Off-pump implantation reduces operative time and intraoperative red cell transfusions but carries a risk of incomplete ventricular coring, which may precipitate pump thrombosis. The benefits of the left thoracotomy approach were seen in the reduced need for intraoperative red cell transfusion and reduced total intensive care unit (ICU) stay for patients who had undergone previous sternotomy. CONCLUSIONS: The Jarvik 2000 has several distinctive features that simplify surgical management and permit flexible application in an expanded range of candidates for LVAD implantation, particularly in patients who have undergone previous sternotomy.