Extrinsic Outflow Graft Obstruction of the HeartMate 3 LVAD: A State-of-the-Art Review.

While notable improvements in survival, incidence of hemocompatibility-related adverse events, hospitalizations and cost have been demonstrated with the only commercially available durable left ventricular assist device, a category of pump malfunctions characterized by outflow graft obstruction has been noted with broader use and clinical follow up of recipients of this technology. Of particular concern, is the accumulation of acellular biodebris between the outflow graft and bend relief covering the outflow graft at its origin with the pump (which we term extrinsic outflow graft obstruction at the bend relief, or EOGO-BR). This process tends to be insidious, occurs late in the postoperative course, can be challenging to diagnose, and can result in significant morbidity and mortality. Herein we provide a review of this complication and outline diagnostic, treatment and preventive strategies.

Inhibition of angiogenesis in the management of refractory gastrointestinal bleeding in patients with LVAD support.

BACKGROUND: Gastrointestinal bleeding (GIB) in patients with continuous flow left ventricular assist devices (CF-LVADs) is often related to GI angiodysplasia (GIAD). We previously reported data on VEGF inhibition with IV bevacizumab in the treatment of LVAD-associated GIAD bleeding, and now present follow-up data on patients treated with IV bevacizumab and/or low-dose oral pazopanib. METHODS: All consecutive adult patients with LVAD-associated GIB from GIAD treated with bevacizumab or pazopanib, from July 20, 2017 to June 22, 2022, were included in the analysis. Data on hospitalizations, GI endoscopic procedures, and blood transfusions were obtained from first admission for GIB up to a median of 35.7 months following treatment initiation (range 1.3-59.8 months). RESULTS: Eleven patients (91% male, mean 69.5 ± 8.9 years) were included. Eight patients (73%) received IV bevacizumab, two patients (18%) received oral pazopanib, and one patient (9%) received bevacizumab followed by pazopanib therapy. We observed a significantly decreased number of annualized hospitalizations for GIB (median difference - 2.87, p = 0.002), blood transfusions (median difference - 20.9, p = 0.01), and endoscopies (median difference - 6.95, p = 0.007) in patients pre- and post-anti-angiogenic therapy (bevacizumab and/or pazopanib). Similarly, a significant improvement in these clinical outcomes was noted in the bevacizumab group with decreased annualized hospitalizations (median difference - 2.75, p = 0.014), blood transfusions (median difference - 24.5, p = 0.047), and number of endoscopies (median differences -6.88, p = 0.006). CONCLUSION: Anti-angiogenic therapy with IV bevacizumab and/or low-dose oral pazopanib appears to provide benefits in patients with LVAD-associated GIB with reduced hospitalizations, blood transfusions, and need for GI endoscopic procedures.

Clinical Characteristics and Outcomes of Clostridioides difficile Infection in Patients With Left Ventricular Assist Device.

The literature regarding Clostridioides difficile infection (CDI) in left ventricular assist devices (LVADs) patients is limited. Therefore, we aimed to characterize the clinical course, risk factors, management, and outcomes of LVAD patients who developed CDI. Adult patients who underwent LVAD placement during 2010-2022 and developed CDI were included. To determine risk factors and outcomes, we matched CDI patients with LVAD patients who did not develop CDI. Each CDI case was matched with up to two control subjects by age, sex, and time from LVAD implantation. Forty-seven of 393 LVAD patients (12.0%) developed CDI. The median time from LVAD implantation to CDI was 147 days (interquartile range 22.5-647.0). The most common CDI treatment was oral vancomycin (n = 26, 55.3%). Thirteen patients (27.7%) required treatment extension because of a lack of clinical response. Three patients (6.4%) developed recurrent CDI. When 42 cases were matched to 79 control subjects, antibiotic exposure within 90 days was significantly associated with CDI (adjusted odds ratio 5.77; 95% confidence interval, 1.87-17.74; p = 0.002). Moreover, CDI was associated with 1 year mortality (adjusted hazard ratio 2.62; 95% confidence interval, 1.18-5.82; p = 0.018). This infection occurs most often within the first year after LVAD implantation and was associated with 1 year mortality. Antibiotic exposure is an important risk for CDI.

Pulmonary Capillary Recruitment Is Attenuated Post Left Ventricular Assist Device Implantation.

There is limited knowledge of pulmonary physiology and pulmonary function after continuous flow-left ventricular assist device (CF-LVAD) implantation. Therefore, this study investigated whether CF-LVAD influenced pulmonary circulation by assessing pulmonary capillary blood volume and alveolar-capillary conductance in addition to pulmonary function in patients with heart failure. Seventeen patients with severe heart failure who were scheduled for CF-LVAD implantation (HeartMate II, III, Abbott, Abbott Park, IL or Heart Ware, Medtronic, Minneapolis, MN) participated in the study. They underwent pulmonary function testing (measures of lung volumes and flow rates) and unique measures of pulmonary physiology using a rebreathe technique that quantified the diffusing capacity of the lungs for carbon monoxide (DLCO) and diffusing capacity of the lungs for nitric oxide before and 3 months after CF-LVAD implantation. After CF-LVAD, pulmonary function was not significantly changed (p >0.05). For lung diffusing capacity, alveolar volume (VA) was not changed (p = 0.47), but DLCO was significantly reduced (p = 0.04). After correcting for VA, DLCO/VA showed a trend toward reduction (p = 0.08). For the alveolar-capillary component, capillary blood volume (Vc) was significantly reduced (p = 0.04), and alveolar-capillary membrane conductance trended toward a reduction (p = 0.06). However, alveolar-capillary membrane conductance/Vc was not altered (p = 0.92). In conclusion, soon after CF-LVAD implantation, Vc is reduced likely because of pulmonary capillary derecruitment, which contributes to the decrease in lung diffusing capacity.

Infections in Patients With Left Ventricular Assist Devices: Current State and Future Perspectives.

Mechanical circulatory support is increasingly being used as bridge-to-transplant and destination therapy in patients with advanced heart failure. Technologic improvements have led to increased patient survival and quality of life, but infection remains one of the leading adverse events following ventricular assist device (VAD) implantation. Infections can be classified as VAD-specific, VAD-related, and non-VAD infections. Risk of VAD-specific infections, such as driveline, pump pocket, and pump infections, remains for the duration of implantation. While adverse events are typically most common early (within 90 days of implantation), device-specific infection (primarily driveline) is a notable exception. No diminishment over time is seen, with event rates of 0.16 events per patient-year in both the early and late periods postimplantation. Management of VAD-specific infections requires aggressive treatment and chronic suppressive antimicrobial therapy is indicated when there is concern for seeding of the device. While surgical intervention/hardware removal is often necessary in prosthesis-related infections, this is not so easily accomplished with VADs. This review outlines the current state of infections in patients supported with VAD therapy and discusses future directions, including possibilities with fully implantable devices and novel approaches to treatment.

Opioid usage after left ventricular assist device implantation: A single center retrospective analysis.

BACKGROUND: Opioid use disorder is a known national concern and extends across multiple populations; however, opioid use in the left ventricular assist device (LVAD) population and subsequent outcomes is not well described. OBJECTIVES: We sought to understand opioid use and patient characteristics among the LVAD population at a single center and associated outcomes after index LVAD hospitalization in relation to opioid use. METHODS: A single center retrospective review of pre-operative and post-operative opioid use was characterized during the index admission for LVAD implantation. Additionally, we reviewed medical records from patients with opioid prescription at hospital discharge stratified by oral morphine equivalents (OME) and refills of opioid prescriptions with analysis of the outcomes of readmission and death after hospital discharge from the index admission for LVAD implantation. RESULTS: Opioid exposed patients in this cohort increased in frequency from 0% of patients in 2007 to a peak of 25.9% of patients in 2013, and gradually declined thereafter to 12.5% in 2017. CONCLUSIONS: Despite the rate of high dose opioid therapy in this cohort, neither opioid use, opioid history, oral morphine equivalents (OME), or opioid refills portended worse survival after LVAD implantation.

Interventricular-Septal Output While Supported on Left Ventricular Assist Device Therapy.

The effects of left ventricular unloading on septal function in patients with left ventricular assist devices (LVADs) have not been well characterized in vivo. The purpose of this study was to evaluate the relationship between markers of septal function with echocardiography in relationship to RV dysfunction and late RV failure after LVAD implantation. A retrospective study was conducted of patients supported on centrifugal-flow LVADs implanted over a 10-year period. Echocardiographic data were collected pre-operatively and up to 2 years after implantation. Interventricular septum (IVS) measurements were taken at end-systole and end-diastole. Interventricular-septal output (ISO) was calculated using the formula: (IVSs-IVSd)×heart rate. A total of 110 patients were included. An immediate and sustained reduction in both lateral annulus systolic velocity (RVS') and TAPSE were observed after implant ( p < 0.0001). However, ISO gradually decreased over time ( p < 0.0001). While ISO was not predictive of late RV failure, a decrease in ISO by 25% or greater from pre-implant to hospital discharge was associated with late RV failure (OR 4.8; 95% CI, 1.4-16.5; p = 0.012) even after adjusting for relevant clinical variables ( p ≤ 0.01 for each model). RV function is known to be influenced by mechanical ventricular interdependence and we demonstrate that measurement of ISO may be a useful marker in assessing RV dysfunction and predicting RV failure in patients following LVAD implantation.

First Report of Proton Beam Therapy in a Patient With a Left Ventricular Assist Device.

A 77 year old man previously implanted with a HeartMate II left ventricular assist device (LVAD) as destination therapy and an implantable cardioverter defibrillator presented with a left upper lobe squamous cell lung cancer. Oncology determined that proton beam therapy was indicated for treatment, and a multidisciplinary team of radiation physicists, radiation oncologists, and LVAD providers developed a protocol to proceed safely. He was successfully treated with combined proton beam radiation therapy and reduced dose chemotherapy. This case demonstrates feasibility and considerations of proton beam therapy for malignancy relevant to patients with implantable cardiac devices including LVADs.

De Ritis-adjusted AST provides comparable efficacy to lactate dehydrogenase as a biomarker for detection of LVAD hemolysis or thrombosis.

BACKGROUND: Lactate hydrogenase (LDH) is a common biomarker utilized in the detection and monitoring of left ventricular assist device (LVAD) hemolysis and thrombosis. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are common laboratory tests that can be used to calculate the De Ritis ratio and the De Ritis adjusted AST. METHODS: A retrospective review of LVAD patients was performed to identify three cohorts of patients: those with confirmed pump thrombosis after device exchange, those with LVAD-related hemolysis who were medically managed without pump exchange, and those who did not meet these criteria and served as the control cohort. Evaluation of AST, AST/ALT ratio (referred to as the De Ritis ratio) as well as AST x (AST/ALT) or the De Ritis-adjusted AST (DRA) was performed. RESULTS: There were 29 patients who underwent device exchange for thrombosis, 25 patients who were diagnosed with hemolysis and treated medically (clopidogrel (N = 6), heparin (N = 13), tirofiban (N = 8), eptifibatide (N = 2), and some received more than one of these treatments), and 425 control patients. A qualitatively comparable relative and absolute rise in DRA and LDH were found in both surgically managed pump thrombosis and suspected device-related hemolysis. CONCLUSIONS: Both AST and LDH as well DRA are significantly associated with pump thrombosis (p < 0.0001 for each). DRA is a potential screening biomarker for hemolysis and device thrombosis in stable left ventricular assist device patients.

Optimal Hemodynamics and Risk of Severe Outcomes Post-Left Ventricular Assist Device Implantation.

Data on pre-implant hemodynamic optimization before continuous flow left ventricular assist device placement (CF-LVAD) with respect to patient-centered outcomes remain limited. Consecutive patients undergoing CF-LVAD implant between 2007 and 2017 were identified. Hemodynamic variables, trends, and laboratory studies were evaluated pre-LVAD implant in a logistic regression model to identify predictors of the primary composite endpoint: the need for right ventricular assist device therapy, the requirement for hemodialysis at 90 days, and 30-day mortality. Multivariate modeling identified three variables significantly associated with the primary endpoint: right ventricular stroke work index (RVSWI), right atrial pressure (RAP), and blood urea nitrogen (BUN); all immediately pre-LVAD, p < 0.01. Optimal dichotomization points were 500 mmHg*ml*m-2, 12 mmHg, and 40 mg/dL. The three-component model identified an AUC of 0.77 (p < 0.0001) for the composite endpoint. Optimization of 2/3 parameters, 1/3, and 0/3 was associated with odds ratios of 3.5 (95% CI, 1.1-11.7), 7.2 (95% CI, 2.1-24.2), and 20.6 (95% CI, 5.3-80.6), respectively, relative to those patients who were fully optimized (3/3 parameters). The number of optimized parameters was also associated with 1-year overall survival (p = 0.02). Low RVSWI, high RAP, and high BUN were independently associated with adverse outcomes after the CF-LVAD implant, demonstrating a stepwise association with severe postimplant adverse events.

Acoustic Properties of Axial and Centrifugal Flow Left Ventricular Assist Devices and Prediction of Pump Thrombosis.

OBJECTIVE: To characterize the properties of the audible tones produced by current left ventricular assist device (LVAD) pumps approved for use, and to ascertain if changes in those may be present in the setting of pump thrombosis. PATIENTS AND METHODS: From August 31, 2016, to January 16, 2020, LVAD recipients consented to have surface recordings obtained using a high-fidelity digital stethoscope. Audio data were analyzed using digital recording and editing software to produce an acoustic spectrogram by Fast Fourier transformation. RESULTS: Recordings were obtained in 53 patient encounters (27 HeartMate II, 19 HeartWare and 7 HeartMate 3). In 12 patients (9 HeartMate II, 3 HeartWare) there was a clinical concern for pump thrombosis. In all patients and pump models, a fundamental frequency was noted, and the second and third harmonics were also clearly detectable. Where thrombosis occurred in the HeartMate II pump, the absolute (normal -46.9 [-57.5,-42.9] dB vs thrombosis -41.4 [-49.8,-26.8] dB; P=.08) and relative (normal 0.72 [0.62, 0.92] vs thrombosis 0.95 [0.86, 1.24]; P=.01) third harmonic frequencies were increased in amplitude. Where paired data were available, an increase in the absolute and relative third harmonic frequencies was observed in all patients. In the case of the HeartWare device, a consistent difference in harmonic amplitudes in the setting of thrombosis could not be identified. CONCLUSION: A consistent pattern of fundamental and harmonic frequencies is common to all LVADs currently approved for use. Alterations in the amplitude of higher order harmonics may signal the onset of pump thrombosis in axial flow LVADs.

Risk of Liver Dysfunction After Left Ventricular Assist Device Implantation.

BACKGROUND: Incident liver dysfunction after left ventricular assist device implantation has been previously associated with adverse outcomes, yet data on perioperative risk markers are sparse. METHODS: We retrospectively reviewed consecutive patients undergoing continuous-flow left ventricular assist device implant between 2007 and 2017 at a single institution. Perioperative variables were evaluated by univariate modeling and adjusted for false discovery rate. Variables most significantly associated with incident Interagency Registry for Mechanically Assisted Circulatory Support-defined liver dysfunction (INT-LD) were evaluated using logistic regression and optimal cutpoints were defined. One-year survival was evaluated using Kaplan-Meier analysis. RESULTS: We included 359 patients (79% male; mean age 59 ± 13 years; 46% ischemic; 64% destination therapy). Lower right ventricular stroke work index at the time of right heart catheterization, higher right atrial pressure 6 hours after right heart catheterization, higher preoperative total bilirubin, longer cardiopulmonary bypass time, and greater volume of intraoperative ultrafiltration were most strongly associated with incident INT-LD (adjusted P < .01 for each). Initial right ventricular stroke work index less than 460 mm Hg∗mL/m2 (odds ratio [OR] 4.6; 95% confidence interval [CI], 2.3 to 9.4), 6-hour right heart catheterization 14 mm Hg or greater (OR 4.3; 95% CI, 2.1 to 8.8), cardiopulmonary bypass time longer than 137 minutes (OR 3.3; 95% CI, 1.8 to 6.2; P < .01 for all), ultrafiltration more than 2.95 L (OR 3.7; 95% CI, 2 to 6.8), and total bilirubin greater than 1.4 mg/dL (OR 2.7; 95% CI, 1.4 to 5) were each strongly associated with risk of INT-LD, which was associated with decreased unadjusted 1-year survival (P < .001). CONCLUSIONS: Right ventricular stroke work index, right heart catheterization, cardiopulmonary bypass time, and ultrafiltration were each more strongly associated with elevated risk of INT-LD after left ventricular assist device implant than total bilirubin. Therefore, optimization of right ventricular hemodynamics and minimizing cardiopulmonary bypass time and ultrafiltration could potentially reduce the risk of liver dysfunction, but these observations require prospective validation.

Associations of depressive symptoms with outcomes in patients implanted with left ventricular assist devices.

OBJECTIVE: We examined characteristics of depressive symptoms in patients who received left ventricular assist devices (LVAD) to assess their effects on negative outcomes post-implantation. METHODS: We retrospectively identified 203 adults with pre-operative PHQ-9 scores who underwent LVAD placement as bridge to transplant (BTT) or destination therapy (DT). We analyzed effects of PHQ-9 total, somatic, and cognitive/affective scores and proportion of patients with clinical depression on all-cause mortality, rehospitalization, major bleeding, and neurologic events post-implantation, controlling for demographics and other medical comorbidities. RESULTS: Mean total PHQ-9 scores did not differ between 81 BTT and 122 DT patients (BTT 6.4 vs. DT 7.5, p = 0.12). A higher proportion of DT patients had clinical depression (BTT 22% vs. DT 39%, p = 0.015). Somatic symptoms accounted for three-quarters of total scores in both groups. PHQ-9 domains were not associated with negative outcomes post-implantation. CONCLUSION: Depression severity did not differ based on implant strategy, but more DT patients had clinical depression. Somatic symptoms were the biggest contributor to depressive symptoms. Pre-implantation PHQ-9 scores were not associated with outcomes, possibly because depression was mild in both groups. Additional work is needed in LVAD patients to better characterize depressive symptoms and their unique effects on clinical course and well-being.

Floating LVAD hardware in an infected hematoma following a traumatic fall.

Left ventricular assist devices (LVAD) are used to support advanced heart failure patients who have failed optimal medical management, meet LVAD criteria, and are deemed to be appropriate surgical candidates. LVAD patients are further advised on symptoms that should prompt notification to the implanting center and are encouraged to contact their LVAD team with device questions and concerns due to morbidity risks unique to this patient population. Mechanical disruption of internal LVAD components is rare and typically requires hospitalization and potentially surgical intervention. External trauma to the LVAD resulting in driveline fracture, torn LVAD outflow grafts, pump displacement, and a kinked inlet cannula have been described.1 Because these occurrences are rare and often unexpected, identification of the root cause may not always be readily apparent. We describe a previously unreported presentation of a patient supported with an LVAD for more than 4 years who was found to have a broken and dislodged LVAD outflow cuff floating in an abdominal hematoma without pump failure.

Predictors and Clinical Outcomes of Vasoplegia in Patients Bridged to Heart Transplantation With Continuous-Flow Left Ventricular Assist Devices.

Background The presence of a durable left ventricular assist device (LVAD) is associated with increased risk of vasoplegia in the early postoperative period following heart transplantation (HT). However, preoperative predictors of vasoplegia and its impact on survival after HT are unknown. We sought to examine predictors and outcomes of patients who develop vasoplegia after HT following bridging therapy with an LVAD. Methods and Results We identified 94 patients who underwent HT after bridging with continuous-flow LVAD from 2008 to 2018 at a single institution. Vasoplegia was defined as persistent low vascular resistance requiring ≥2 intravenous vasopressors within 48 hours after HT for >24 hours to maintain mean arterial pressure >70 mm Hg. Overall, 44 patients (46.8%) developed vasoplegia after HT. Patients with and without vasoplegia had similar preoperative LVAD, echocardiographic, and hemodynamic parameters. Patients with vasoplegia were significantly older; had longer LVAD support, higher preoperative creatinine, longer cardiopulmonary bypass time, and higher Charlson comorbidity index; and more often underwent combined organ transplantation. In a multivariate logistic regression model, older age (odds ratio: 1.08 per year; P=0.010), longer LVAD support (odds ratio: 1.06 per month; P=0.007), higher creatinine (odds ratio: 3.9 per 1 mg/dL; P=0.039), and longer cardiopulmonary bypass time (odds ratio: 1.83 per hour; P=0.044) were independent predictors of vasoplegia. After mean follow-up of 4.0 years after HT, vasoplegia was associated with increased risk of all-cause mortality (hazard ratio: 5.20; 95% CI, 1.71-19.28; P=0.003). Conclusions Older age, longer LVAD support, impaired renal function, and prolonged intraoperative CPB time are independent predictors of vasoplegia in patients undergoing HT after LVAD bridging. Vasoplegia is associated with worse prognosis; therefore, detailed assessment of these predictors can be clinically important.