LVAD Population Research Articles

1587. Analysis of Breakthrough Blood Stream Infections in Left Ventricular Assist Device Recipients Managed With Chronic Antimicrobial Suppressive Therapy

BackgroundLeft ventricular assist devices (LVAD)-associated infections are associated with fivefold higher 1-year mortality. Published literature is insufficient to inform clinicians regarding optimal management of bloodstream infection (BSI) in patients LVAD recipients. In particular, it is unclear which episodes of BSI may result in occult hematogenous seeding of the device surfaces, and therefore should be managed with chronic suppressive therapy (CAS). We aim to describe BSI, CAS, and breakthrough BSI in our LVAD population.MethodsWe retrospectively reviewed 332 episodes of all LVAD infections at Mayo Clinic from 2007 to 2015. We categorized BSI as LVAD related/associated and LVAD nonrelated as defined by established criteria in the cardiac device literature. Our primary outcome was to describe breakthrough BSI in LVAD related and nonrelated infections in patients receiving CAS and those who were not.ResultsWe identified 68 episodes of bacteremia in our LVAD population. Of these, 55 were proven BSI (see Fig 1). In our study cohort, 45/55 (82%) were male and median patient age was 62 years. A majority of LVAD implants were destination therapy 34/55 (62%) and 35/55(64%) had a central line in place at the time of BSI. Twenty patients had non-VAD-related BSI and nine of these (9/20, 45%) patients were placed on CAS with two of these (2/9, 22%) had subsequent breakthrough BSI, whereas 11/20 (55%) were not placed on CAS with no breakthrough infections seen (Figure 1).ConclusionOur preliminary data suggest that routine use of CAS for non-VAD-related BSI is not necessary as only a minority go on to have breakthrough BSI. Limiting unnecessary use of antibiotics will have significant implications for stewardship and preventing emergence of resistance. Disclosures L. M. Baddour, UpToDate: Collaborator, Royalty payment. M. R. Sohail, TyRx Inc: Investigator, Research support; Medtronic Inc: Investigator, Research support; Medtronic Inc: Consultant, Speaker honorarium; Spectranetics: Consultant, Speaker honorarium; Boston Scientific Corp: Consultant, Speaker honorarium.

Gender and Diastolic Dysfunction May be the Driver of Failure of Myocardial Recovery Following LVAD Implantation

LVADs offer a rare chance of myocardial recovery. Such recovery has historically been measured based on explantation rates—a metric that fails to capture progressive events prior to explantation. The objective was to assess ventricular function amongst LVAD population.

Increased Pump Speed is Associated with Reduced Rates of Stroke on HeartMate II LVAD Support

Higher pump speeds have recently been associated with reduced rates of pump thrombosis in the HeartMate II LVAD population. Whether pump speed is associated with stroke has not been well established. In this analysis we use a single center cohort to determine the association with discharge speed and all-cause stroke.

Utilization and Outcomes for BiVADs in Pedimacs Patients

In the Berlin Heart IDE trial, BIVAD patients had worse outcomes than LVAD patient, but this analysis assumed the two patient groups were similar, ignoring the likelihood that BIVAD patients had RV failure. We aimed to compare outcomes in pediatric patients supported with BiVADs to a matched LVAD population.

Altered regulation of cardiac ankyrin repeat protein in heart failure

BackgroundLeft ventricular assist devices (LVADs) have revolutionized and improved the care of the sickest heart failure (HF) patients, and it is imperative that they receive appropriate ventricular unloading. Assessing this critical parameter with current methodologies (labs, imaging) is usually suboptimal in this patient population. Hence it is imperative to elucidate the molecular underpinnings involved in ventricular unloading. We have previously identified the cytoskeletal protein βII spectrin as an essential nodal protein involved in post-translational targeting and βII spectrin protein levels are significantly altered in multiple forms of human and animal HF. We therefore hypothesized that the βII spectrin pathway would play a critical role in LVAD remodeling. MethodsHuman heart failure samples were obtained from patients undergoing heart transplantation. Wild type (WT) mice and our previously validated βII spectrin conditional knock out (βII cKO) mice were used for animal experiments. Transaortic constriction (TAC) was performed on WT mice. Protein expression was assessed via immunoblots, and protein interactions were assessed with co-immunoprecipitation. Transcriptome analysis was performed using isolated whole hearts from control adult WT mice (n = 3) compared to βII cKO spectrin mice (n = 3). ResultsWe report that hearts from mice selectively lacking βII spectrin expression in cardiomyocytes displayed altered transcriptional regulation of cardiac ankyrin repeat protein (CARP). Notably, CARP protein expression is increased after TAC. Additionally, our findings illustrate that prior to LVAD support, CARP levels are elevated in HF patients compared to normal healthy controls. Further, for the first time in a LVAD population, we show that elevated CARP levels in HF patients return to normal following LVAD support. ConclusionOur findings illustrate that CARP is a dynamic molecule that responds to reduced afterload and stress, and has the potential to serve as a prognostic biomarker to assess for an adequate response to LVAD therapy.

Capsule Endoscopy in Left Ventricular Assist Device Patients: Retrospective Review of Efficacy and Necessity

Background
 Capsule endoscopy (CE) is mainstream in the evaluation of obscure gastrointestinal bleeding (GIB) in the general population. However, the diagnostic and therapeutic impact of CE in LVAD patients susceptible to transient bleeding remains largely unexplored. This study aimed to assess the benefits of CE in the evaluation of LVAD associated GIB.
 Methods
 Retrospective review of patients implanted with a continuous flow LVAD who underwent inpatient capsule endoscopy (CE) between January 2014 and May 2017 at our center. Identification of lesions with high bleeding potential or presence of frank blood were considered abnormal findings on CE study.
 Results
 Twenty-five inpatients who underwent 41 CE were identified. All patients presented with GIB and had preceding negative upper endoscopy and colonoscopy in the past 4 weeks. On the first capsule in each patient, 19 had interpretable images, abnormal findings were detected in 5 patients (high risk lesion in 3, frank blood in 2), four of these underwent an enteroscopy and only 2 (8%) patients had confirmation of the capsule findings with APC treatment (true positive). Excluding patients with malfunction, LVAD interference and poor bowel prep, 14 patients had negative/equivocal CE, of which 4 underwent enteroscopy due to continued bleeding and 2 of these patients had treatable culprit lesions (false negative). A total of 17 (68%) patients were discharged without any therapeutic intervention irrespective of the success or findings on CE due to clinical stabilization. Twenty patients (80%) had recurrence in a mean 154 days. As expected, repeat capsules in the same admission increased the diagnostic yield (p=0.031). Only nine patients (36%) had capsule-image evidence of reaching the cecum while 4 patients (16%) had retention which had to be retrieved without further complication.
 Conclusions
 This study demonstrated that evaluation of GIB with CE is feasible and safe but was associated with a low diagnostic yield and low conversion to therapeutic intervention. With a true positive yield of 4% in our cohort, the efficacy and cost-effectiveness of CE in the LVAD population is debatable. The role of CE in LVAD patients may need to be reevaluated. An identification of patients who would benefit from a capsule-first approach would allow optimum utilization of resources and reduce healthcare expenditure.

158 - Heart Failure Hospitalizations in a Contemporary LVAD Population

Introduction: Despite left ventricular unloading, LVAD recipients continue to experience heart failure (HF) hospitalizations. Our objective was to characterize the short and long term rates and risk factors for HF hospitalizations in a contemporary LVAD population. Methods and Results: Between January 2010 and December 2016, 266 HF patients were discharged on continuous flow LVAD support after an index hospitalization for device implantation (FDA approved devices). Subject characteristics are shown in Table 1. Patients were followed for all cause and HF hospitalizations for up to 6.9 years (median support time 4.4 years; total time 423-person-year). HF was the third most common cause of hospitalization (after bleeding and infection). Eighty-eight patients (33%) experienced 175 HF hospitalizations (range 1–12; 56% had only one HF hospitalization). The rate of HF hospitalization decreased to the lowest rate between years 2 and 3, but started to increase thereafter, in both centrifugal and axial flow pumps (Fig. 1). In a multivariable model, history of hypertension (HR 1.83, 95% CI 1.12–3.11; P = .01), BUN at implant (HR 1.14 per 10 mg/dl, 95% CI (1.01–1.26), P = .03) and male sex (HR 1.71, 95% CI 1.03–3.00; P = .04) were independent predictors of HF hospitalization. The rates of HF hospitalizations were no different in centrifugal compared with axial flow pumps.. Conclusion: Whereas the rate of HF hospitalization declines after the first two years of LVAD support, it increases thereafter. With the expanding use of LVADs and improved survival on support, it is imperative to characterize the role of the right and/or left ventricles in causing late HF and define guided therapeutic approaches.Table 1VariableMean ± SD or N (%frequency)Age at implant, years55 ± 12Sex, women70 (26%)Black race182 (68%)BMI at implant29 ± 6Hypertension173 (65%)Diabetes mellitus101 (38%)Ischemic etiology90 (34%)Creatinine, mg/dl1.31 ± 0.6BUN, mg/dl24 ± 15Device type:HMII110 (41%)HVAD156 (59%)Intention of Implant:Bridge to decision32 (12%)Bridge to transplant139 (52%)Destination therapy95 (36%) Open table in a new tab

(1358) - Initiation of a Standardized International Normalized Ratio Management Protocol Reduces Out of Range Days in an Ambulatory LVAD Population

(1358) - Initiation of a Standardized International Normalized Ratio Management Protocol Reduces Out of Range Days in an Ambulatory LVAD Population

HCV false positive immunoassays in patients with LVAD: A potential trap!

BackgroundLeft ventricular assist devices (LVAD) are a therapeutic choice for patients with advanced heart failure prior cardiac transplantation. Patients with a LVAD implant are frequently monitored for hepatitis C virus (HCV) as a positive result may be an exclusion criterion for transplantation. ObjectivesTo determine the rate of false positive results with immunoassays for HCV antibodies in a LVAD population. Study designBetween June 2011 and January 2015, HCV antibody testing using a chemiluminescent immunoassay (CLIA) (Liaison, Diasorin) was performed for 32 patients prior and post LVAD implantation. A HCV reactive result by CLIA was repeated and further tested by an enzyme linked fluorescent assay (ELFA) (VIDAS, bioMérieux). For patients with a positive HCV CLIA and ELFA test, immunoblot and HCV RNA detection were performed. ResultsPrior to LVAD implantation, all patients showed a negative HCV serology. After LVAD implantation, 19 patients (59%) had positive results for HCV antibody using CLIA and ELFA technologies. The HCV immunoblot was negative for 17 patients and indeterminate for two patients. For 15 patients, HCV RNA detection was performed and was undetectable. Actually, no HCV infections were observed among those who were tested for HCV RNA. ConclusionsHCV serological tests routinely used in our laboratories are not reliable in patients with cardiac devices. A positive CLIA and/or ELFA reaction in patients with a LVAD should be confirmed by HCV immunoblot and by HCV RNA PCR detection in order to rule out a HCV infection.

Damaging Cardiac and Cancer Genetic Variants in the LVAD Population

Abstract
 Background: Next generation sequencing technology, coupled with population genetic databases, have made broad genetic evaluation relatively inexpensive and widely available. Our objective was to assess the prevalence of potentially damaging cancer and cardiac gene variants in advanced non-ischemic cardiomyopathy patients.
 Methods: Explanted human heart tissue procured at LVAD placement was obtained from the University of Nebraska Medical Center Heart Tissue Bank. Genomic DNA was isolated from tissues and amplified by PCR using targeted ampliseq primer pools from an inherited disease panel. Individual libraries were amplified by emulsion PCR on Ion Sphere particles and sequencing was performed on a PGM sequencer (Ion torrent) using the Ion 316 chip. The Ion Torrent browser suite was used to map the reads and call the variants. The identified single nucleotide polymorphisms, insertions, and deletions were then annotated and characterized with ANNOVAR. Non-synonymous mutations with a population frequency of less than or equal to 1% were identified and analyzed utilizing an open source integrative genomics viewer. Amino acid substitution effects on protein function were determined by a bioinformatics algorithm. Myocardial recovery was defined as an improvement in EF to greater than 45% at three months post implant.
 Results: Our sample population included 12 males and 2 females with an average age of 49 and an average EF at presentation of 17%. Damaging cardiac gene variants were present in 11/14 patients. Only 1 of the 11 patients with damaging cardiac gene variants improved their ejection fraction to greater than 45% post LVAD. Two of the 2 patients without mutations improved their ejection fraction to greater than 45%, p-value=.04. Nine of the 14 patients in this population had damaging oncogene mutations.
 Conclusions: Damaging variants in cancer and cardiac genes are common in end-stage non-ischemic cardiomyopathy patients undergoing LVAD placement. Genetic variation likely contributes to disease progression and cancer risk.

(613) - Multidisciplinary Approach to Managing GI Bleeding in the LVAD Population

(613) - Multidisciplinary Approach to Managing GI Bleeding in the LVAD Population

Six-minute walk distance predicts VO₂ (max) in patients supported with continuous flow left ventricular assist devices.

Six-minute walk distance (6MWD) and maximal oxygen uptake (VO₂ max ) are used as prognostic tools in patients with heart failure (HF). Whether these tests provide similar information in the LVAD population is not known. Eight patients supported with VentrAssist rotary blood pump LVADs, underwent three days of testing that included 6MWD and VO₂ max at normal, high or low speeds, generating twenty-four paired results. The mean 6MWD was 438 (+/- 90 SD) m and the mean VO₂ (max) was 14.12 (+/-1.87) ml/kg/min. There was a modest correlation between VO₂ (max) and 6MWD (r = 0.56 p = 0.004), which improved (r = 0.72 p = 0.002) when patients with higher resting Pro BNP levels and larger left ventricular end diastolic diameters (LVEDD) were excluded. 6MWD is correlated with VO₂ (max) in LVAD supported patients, with higher correlations in patients with better underlying cardiac function.

(520) - Decreased Renal Function Correlates With Severity of Aortic Regurgitation But Not LV EF or RV Function With LVAD Therapy

Aortic regurgitation is recognized as a developing clinical problem in the LVAD population. Correlation of AR with renal dysfunction with LVAD has not been investigated. While the impact of LVAD on renal function is described, the correlation to improvement in LV and RV function remains unclear. Our objective was to evaluate the relationship of serum creatinine to LV EF, RV function and AR in the LVAD population.

(335) - A Zero 90-Day Mortality After Lung Transplantation - What Is the Price?

s S127 Methods: We retrospectively examined medical records of 71 patients who underwent placement of a HeartMate II or HeartWare LVAD at our institution. Insurance status was determined at the time of implantation. Medical record was examined to assess clinical outcomes such as survival, attainment of insurance, and transplant candidacy. Results: We identified 14 uninsured patients (20% of total LVAD population) who underwent LVAD implantation. Uninsured patients were younger and less likely to have ischemic etiology for heart failure than insured patients (see table). All patients postoperatively eventually attained insurance benefits (Medicare or Medicaid). Clinical outcomes were as follows: 7 patients (50%) were eventually listed for transplantation with 4 undergoing transplant and 3 currently listed, 5 patients (36%) with ongoing support as destination therapy, and 2 deaths (14%) within the first year (cerebrovascular accident in both). Conclusion: Uninsured patients can undergo LVAD implantation with successful outcomes. LVAD implantation can allow for patients to stabilize while insurance is obtained, allowing for eventual listing for transplantation. Given the high costs associated with chronic heart failure, further research is needed to determine if LVAD placement in uninsured advanced heart failure patients can reduce overall health care expenditures. Patient Demographics Insured(n = 57) Uninsured(n = 14) p value Age (yrs) 54 ± 11 42 ± 11 < 0.01 Male gender (%) 74% 79% NS Ischemic etiology (%) 52% 36% < 0.01 INTERMACS profile 2.4 ± 1.0 2.0 ± 1.0 NS

Bridging with Half-Therapeutic Dose Enoxaparin for Sub-Therapeutic INR among Outpatients with Ventricular Assist Devices

Background: Long-term anticoagulation therapy with warfarin is recommended for LVAD patients. Compared to other warfarin-treated patients, the LVAD population has a higher rate of suboptimal INRs and a lower average time in the therapeutic window. Suboptimal anticoagulation is a major reason for hospital readmission. We describe our experience with the use of half-dose enoxaparin (0.5 mg/kg/dose) bridging therapy, as a potential alternative to hospital readmission for LVAD-patients with subtherapeutic INRs who may be at higher risk of thrombotic events. Methods: LVAD outpatients with sub-therapeutic INRs were selected to receive half therapeutic dose enoxaparin as bridge therapy based on our VAD anticoagulation protocol. Selection criteria included current INR, VAD type and timing of implantation, history of bleeding or thrombotic events, renal function, medication adherence, and ability to effectively administer enoxaparin injections. The general threshold for bridging was an INR ! 1.6. Enoxaparin was dosed as 0.5 mg/kg every 12 hours. Outpatient INR monitoring and follow-up was conducted by the VAD Coordinator and pharmacist. Within 24 hours of initiation of therapy, a pharmacist telephoned the patient to reinforce proper administration technique and to answer medication-specific questions. Additional telephone communications were conducted by the pharmacist and VAD Coordinator to assess for bleeding complications and duration of therapy. Patients are monitored routinely for thrombus at each ambulatory clinic visit. Results: During the initial 6 months of this program, 15 patients (11 HeartMate II, 3 HeartWare LVAD, 1 Heartware BiVad) were treated with half-dose enoxaparin. The mean INR upon initiation of therapy was 1.4 (range 1.2 to 1.7). Patients received an average of 7.2 enoxaparin doses (range 4 to 14) for a mean duration of therapy of 3.5 days (range 2 to 7). In total, 108 doses were administered accounting for 54 patient days of therapy. No patient was admitted to a hospital due to bleeding or thrombotic events. Minor bleeding, described as mild bleeding at the injection site and increased bruising, was reported in 5 patients (30%). During the observation period, 14 patients (93.3%) completed the protocol with achievement of a therapeutic INR; one patient discontinued therapy due to hospital admission not related to anticoagulation management. Conclusion: In this small series, half-dose enoxaparin appears to be a feasible strategy to bridge selected ambulatory VAD patients with sub-therapeutic INRs. Further investigation is needed to determine its safety and efficacy in a larger population of patients

Cognitive Behavioral Therapy by iPad for Caregivers: A Pilot Study

Background: Long-term anticoagulation therapy with warfarin is recommended for LVAD patients. Compared to other warfarin-treated patients, the LVAD population has a higher rate of suboptimal INRs and a lower average time in the therapeutic window. Suboptimal anticoagulation is a major reason for hospital readmission. We describe our experience with the use of half-dose enoxaparin (0.5 mg/kg/dose) bridging therapy, as a potential alternative to hospital readmission for LVAD-patients with subtherapeutic INRs who may be at higher risk of thrombotic events. Methods: LVAD outpatients with sub-therapeutic INRs were selected to receive half therapeutic dose enoxaparin as bridge therapy based on our VAD anticoagulation protocol. Selection criteria included current INR, VAD type and timing of implantation, history of bleeding or thrombotic events, renal function, medication adherence, and ability to effectively administer enoxaparin injections. The general threshold for bridging was an INR ! 1.6. Enoxaparin was dosed as 0.5 mg/kg every 12 hours. Outpatient INR monitoring and follow-up was conducted by the VAD Coordinator and pharmacist. Within 24 hours of initiation of therapy, a pharmacist telephoned the patient to reinforce proper administration technique and to answer medication-specific questions. Additional telephone communications were conducted by the pharmacist and VAD Coordinator to assess for bleeding complications and duration of therapy. Patients are monitored routinely for thrombus at each ambulatory clinic visit. Results: During the initial 6 months of this program, 15 patients (11 HeartMate II, 3 HeartWare LVAD, 1 Heartware BiVad) were treated with half-dose enoxaparin. The mean INR upon initiation of therapy was 1.4 (range 1.2 to 1.7). Patients received an average of 7.2 enoxaparin doses (range 4 to 14) for a mean duration of therapy of 3.5 days (range 2 to 7). In total, 108 doses were administered accounting for 54 patient days of therapy. No patient was admitted to a hospital due to bleeding or thrombotic events. Minor bleeding, described as mild bleeding at the injection site and increased bruising, was reported in 5 patients (30%). During the observation period, 14 patients (93.3%) completed the protocol with achievement of a therapeutic INR; one patient discontinued therapy due to hospital admission not related to anticoagulation management. Conclusion: In this small series, half-dose enoxaparin appears to be a feasible strategy to bridge selected ambulatory VAD patients with sub-therapeutic INRs. Further investigation is needed to determine its safety and efficacy in a larger population of patients

Type 2 Cardiorenal Syndrome in the Left Ventricular Assist Device (LVAD) Population

Purpose Type 2 Cardiorenal Syndrome after LVAD has not been well evaluated in patients with Mechanical Circulatory Support. It has been observed over time that a subset of patients continues to develop worsening renal function over time despite maximal medical therapy and LVAD support. It also appears that these patients maintain higher Doppler pressure recordings over time despite aggressive blood pressure management. Methods and Materials We performed a retrospective chart review of all 27 Destination Therapy patients who survived more than one year after HeartMate II implantation between 2008 and 2011. Doppler pressure readings were obtained via manual blood pressure cuff and Doppler Ultrasound and recorded at time of discharge after LVAD implantation and again at one year follow up visit. Renal function was assessed via Modification of Diet in Renal Disease (MDRD) equation to estimate GFR at time of discharge and again at one year follow up. Results The mean Doppler pressure recorded at time of discharge post-LVAD implantation was 86.2 mm Hg. The mean doppler pressure recorded at one year post implant was 98.3 mm Hg (p = 0.0191). The mean GFR at time of discharge was 96.28 + 5.99 ml/min while at one year was 71.30 ml/min (p= 0.015). The average increase in beta blocker dose over one year was 82% (p = 0.0091). The average increase in ACE/ARB dose over one year was 114% (p=0.08, NS). Conclusions Cardiorenal Syndrome in the LVAD population is not well understood. We have demonstrated that there is a statistically significant decline in GFR to stage II Chronic Kidney Disease, with a simultaneous rise in doppler pressure over one year in patients after LVAD implantation. It is unclear if the continuous flow LVADs contribute to this phenomenon and what role the renin-angiotensin-aldosterone axis may play in this patient population, suggesting that further investigation is required.

Preoperative CHA2DS2-VASC Score Predicts Neurologic Complications in Continuous-Flow (CF) Left Ventricular-Assist Device (LVAD) Patients

Purpose Neurologic events are a devastating complication of LVAD support. Pre-LVAD stroke risk scores are lacking. CHA 2 DS 2 -VASC is an established risk score for ischemic stroke (iCVA) in patients with atrial fibrillation (AF). We hypothesized that it might have predictive value in CF LVAD recipients. Methods and Materials Records for recipients of currently available durable CF LVADs were reviewed. Cox proportional hazards modeling was used to determine association between pre-LVAD variables and: 1) post-LVAD iCVA; or 2) either iCVA or transient ischemic attack (TIA). Patients were censored at death, explant, or ongoing support. In addition to CHA 2 DS 2 -VASC parameters (heart failure; hypertension; age; diabetes; gender; prior iCVA or TIA; vascular disease including myocardial infarction), we tested pre-LVAD Intermacs profile, device type, comorbidity requiring anticoagulation (deep vein thrombosis, pulmonary embolism, LV thrombus, AF), positive heparin antibody, and serum sodium (Na) and albumin (Alb). Lower Na and Alb are predictors of post-LVAD stroke (Kato, J Hrt Lung Transpl 2012;31:1). No patient had a diagnosed hypercoagulable state. Results Of 103 CF LVAD implants (excluding replacements), data were available for 100: 42 Jarvik; 53 Heartmate II; 5 Heartware. 11 (11%) had iCVA, 5 (5%) had TIA, and 1 (1%) had both. Incidence did not differ among devices. For iCVA, CHA 2 DS 2 -VASC was the only significant (at p 2 DS 2 -VASC 2 DS 2 -VASC and Alb were significant predictors. However, the effect of Alb (higher risk with higher Alb) was opposite that shown by Kato et al. No patient with CHA 2 DS 2 -VASC Conclusions In our CF LVAD population, pre-LVAD CHA 2 DS 2 -VASC predicted post-LVAD iCVA or TIA. The Alb effect was incongruent with published data and may require further investigation. We have incorporated this risk score into our pre-LVAD evaluation and plan prospective validation.