Device Exchange and Thrombolytic Therapy for Left Ventricular Assist Device Thrombosis

The 17th Annual Scientific Meeting



S17

HFSA

Neurohormones/Cytokines 043 Atrial Tachyarrhythmias among Patients on Continuous Flow LVAD Support: Incidence, Prevalance and Clinical Outcomes Christopher M. Bianco, Valeria Duarte, Deepak Pattanshetty, Matthew Bunte, Maria Mountis, Cantillon J. Daniel; Cleveland Clinic, Cleveland, OH Introduction: Atrial tachyarrhythmias, including atrial fibrillation (AF) and atrial flutter (AFL), are common among patients on LVAD support. However, the incidence, prevalence and influence on clinical outcomes remains poorly characterized. Objective/Hypothesis: To define the clinical characteristics and compare outcomes among patients with and without atrial tachyarrhythmias on continuous flow LVAD support. AF/AFL patients are hypothesized to demonstrate worse outcomes. Methods: Multi-variable analysis of Cleveland Clinic registry of Heart Mate II (HMII) LVAD recipients between 2007 and August 2012 including atrial arrhythmia data pre and post LVAD, survival outcomes and stroke/TIA events. Results: Among 252 pts (Age 54.4 6 13.8, 79% male), the AF prevalence is 140/252 (56%), and AFL prevalence 33/252 (13%) pts. New AF during LVAD support occurred in 42/154 (27%) pts and new AFL in 17/237 (7%) pts. In comparing patients with AF/AFL (n5149/252, 59%) to those without AF/AFL (n5103/252, 41%), the TIA/stroke event rates were similar (AF/AFL n515/149, 10% vs. none n517/103, 17%; p50.10) with fewer warfarin ineligible pts in AF/AFL group (AF/AFL n511/149, 7% vs. none 12/103, 12%; p50.05) and similar target INRs above the nominal 1.7-2.2 range (Above-nominal INR: AF/AFL 45/138, 35% vs. none 30/81, 33%, p50.8). Survival outcomes over median 305 days follow-up (25th/75th quartiles 108 days, 661 days) were similar between the groups (KM curve figure 1, log-rank p50.9). Conclusion: Atrial tachyarrhythmias in the form of AF and AFL are common among patients on LVAD support, but do not appear to influence overall survival and yield similar stroke/TIA event rates.

vs RVF: 1.3560.58, P!0.01). RA pressure and RA to pulmonary capillary wedge pressure ratio (RA/PCWP) were also associated with RVF (Table 1). Other previously identified markers of RV function including RV stroke work index, mean pulmonary artery pressure, qualitative RV dysfunction (RVD) by 2D echo, and laboratory parameters were not associated with RVF (Table 1). After adjusting for RA pressure in a multivariate model, PaPi remained an independent predictor of RVF. A trend toward reduced survival (censored for transplant) at 180 days was observed in the RVF group (No RVF: 86% vs. RVF: 67%, P50.059). Conclusions: PaPi is a readily available and easily derived baseline variable associated with RVF following LVAD surgery. A larger cohort is necessary to identify optimal PaPi thresholds with which to guide clinical decision making was well as to evaluate model performance of a risk prediction rule incorporating PaPi. Table 1. Baseline variables of patients undergoing LVAD surgery

Age (years) Gender (%male) Destination Therapy (%) Ischemic CM (%) BUN Cr AST INR Moderate-severe RVD (%) HR (bpm) MAP (mmHg) RA (mmHg) mPAP (mmHg) PCWP (mmHg) CI (L/min/m2) TPG (mmHg) RA/PCWP RVSWI PAPI

All patients (n5104)

No RVF (n583)

RVF (n521)

P values

55.9612.1 79 25

55.8612.7 80 25

56.269.6 76 24

0.90 0.77 1.00

39 29618 1.4460.59 776285 1.5260.79 24

43 30618 1.4860.63 776315 1.5560.88 24

24 29616 1.3260.43 736169 1.4160.43 24

0.14 0.88 0.29 0.96 0.53 1.00

91615 7668 1265 3569 2467 2.4560.68 11.665.9 0.5060.20 4.5263.13 2.4361.36

92616 7668 1064 3669 2467 2.4260.66 11.665.4 0.4360.14 4.4562.50 2.7161.36

89611 7568 1765 3369 2267 2.5560.76 11.867.9 0.7960.13 4.7964.76 1.3560.58

0.45 0.51 !0.0001 0.29 0.17 0.44 0.87 !0.0001 0.67 !0.0001

045 Device Exchange and Thrombolytic Therapy for Left Ventricular Assist Device Thrombosis Kevin Morine, Michael Kiernan, Navin Kapur, Jenica Upshaw, Duc Pham, David Denofrio; Tufts Medical Center, Boston, MA

044 Pulmonary Artery Pulsatility Index as a Novel Marker of Right Ventricular Failure Following LVAD Surgery Kevin Morine, Michael Kiernan, Navin Kapur, Robert Baumgartner, Duc Pham, David Denofrio; Tufts Medical Center, Boston, MA Background: The significance of reduced pulse pressure in the right-sided circulation as a marker of right ventricular dysfunction prior to LVAD surgery remains uncertain. We evaluated the pulmonary artery pulsatility index (PaPi), a recently described hemodynamic metric, as a baseline predictor of post-operative RV failure following LVAD surgery. Methods: We conducted a retrospective review of 104 consecutive LVAD implantations at our hospital. Demographic, clinical, hemodynamic and echocardiographic data were evaluated for their association with the development of RVF. RVF was defined as need for RVAD or inotrope dependence for greater than 14 days. PaPi was calculated as [(systolic pulmonary artery pressure-diastolic pulmonary artery pressure)/right atrial (RA) pressure]. Univariate analysis was performed to identify baseline predictors of RVF. Multivariate logistic regression was used to adjust for baseline RA pressure. Results: RVF occurred in 21 of 104 patients (20%); all cases were due to prolonged inotropes. PaPi was lower among patients with RVF compared to those without (no RVF: mean 2.716 SD1.36

Background: Optimal management strategies for continuous-flow LVAD thrombosis (LVAD-T) have not been determined. We describe our experience with 11 pts managed for LVAD-T receiving device exchange and/or thrombolytic therapy (TPA). Methods: A chart review of pts managed for LVAD-T from 1/1/2010 to 4/1/2013 was performed. Thrombus was suspected in the setting of unexplained hemolysis with lactate dehydrogenase (LDH) O4 times ULN (700 IU/L). Treatment options for LVAD-T were made on a case-by-case basis with involvement of the patient and caregivers. Pts were considered for urgent LVAD exchange or TPA if they were hemodynamically unstable. LVAD exchange was also considered for cardioembolic events or failure to respond to TPA. Pts were otherwise treated first with a trial of antithrombotic therapy with escalation to VAD exchange or TPA if conservative therapy failed. Success of TPA was defined as thrombus resolution without serious adverse event or need for LVAD exchange. Success of VAD exchange was considered as long-term survival. Among pts receiving TPA, alteplase was administered (0.75-1 mg/min) either intravenously (n51; 100 mg) or via an intracavitary approach (n54; 38-90 mg). Results: 20 of 116 pts presented with LVAD-T. 11 of 20 pts were managed with LVAD exchange and/or TPA. 5 pts underwent LVAD exchange, 5 pts were given TPA and 1 pt given TPA required exchange for recurrent LVAD-T. In addition to hemolysis, presentation included heart failure symptoms (5), VAD abnormalities (8), or thromboembolic event (3). Mean peak LDH was 15606900 IU/L. Two pts presented with cardiogenic shock and underwent urgent LVAD exchange. 9 pts were initially managed with antithrombotic therapy alone (unfractionated heparin, eptifibatide, or bivalirudin). Due to non-response, 5 of these pts were transitioned to TPA and 4 underwent VAD exchange. Adverse events included 1 intracranial hemorrhage (TPA), 1 gastrointestinal bleed with transfusion (exchange) and 2 mediastinal hematomas (TPA-1, exchange-1). Among 6 pts initially undergoing LVAD exchange, 4 (67%) were transplanted or are alive on LVAD support and 2 died. There was 1 recurrence at 58 days in the new LVAD, treated with bivalirudin until transplant. Among 5 pts receiving TPA, 2 died (40%) and 3 were discharged. There was one recurrence at 13 days requiring exchange. The overall success of TPA at 30 days was 40% (2 pts). Conclusions: LVAD-T is associated with significant morbidity. In our

S18 Journal of Cardiac Failure Vol. 19 No. 8S August 2013 limited experience, success was greater with LVAD exchange compared to TPA; however recurrence after exchange is possible. In the absence of data from larger cohorts, individual pt characteristics and preferences should guide decision making for this event.

046 Arterial Stiffness and Vascular Endothelial Function in Patients with LongTerm Continuous-Flow Left Ventricular Assist Devices Nani Morgan, Patrick Warner, Michael Kiernan, Adeeb Al-Quthami, Youssef Rahban, Duc Thinh Pham, David DeNofrio, Richard Karas, Jeffrey Kuvin; Tufts Medical Center, Boston, MA Introduction: Although surgically-placed continuous-flow left ventricular assist devices (cf-LVADs) improve cardiac output, the consequence of long-term continuous flow on peripheral vascular function, a significant predictor of adverse outcomes, remains unclear. Hypothesis: We hypothesized that patients (pts) with cf-LVADs would have increased arterial stiffness and diminished vascular endothelial function compared to pts with chronic heart failure (HF) and heart transplant (HT) recipients. Methods: We compared pts with at least 6 months of cf-LVAD support (n520) to pts with medically managed chronic HF (n519) and HT recipients (n519). Digital vascular function measurements with peripheral artery tonometry were utilized to assess arterial stiffness (augmentation index, AIx) and microvascular endothelial function following 5 minutes of arm arterial occlusion (reactive hyperemia index, RHI). Brachial artery ultrasound was used simultaneously to assess endothelial-dependent flow mediated dilation (FMD) of the conduit arteries. Results: Compared to HT recipients, pts with cf-LVADs demonstrated significantly higher AIx (23.75 6 20.35 vs. 5.58 6 10.24; p50.006) and lower RHI (1.38 6 0.51 vs. 1.94 6 0.49; p50.01) (Table 1). Pts with cf-LVADs demonstrated higher AIx than those with chronic HF (23.75 6 20.35 vs. 10.84 6 17.63; p50.07), however those differences did not reach statistical significance. There were no significant differences in RHI between cfLVAD and chronic HF pts. In addition, there were no significant differences in FMD between cf-LVAD pts and HT recipients, or cf-LVAD and chronic HF pts. Conclusion: This is the first demonstration that pts with long-term cf-LVADs have increased arterial stiffness and diminished microvascular endothelial function compared to HT recipients. These findings also suggest that, despite an increase in cardiac output, pts with cf-LVADs have increased arterial stiffness compared to those with chronic HF. The mechanisms behind these vascular findings remain unclear, but might be related to reduced pulsatility. The impact of persistent abnormal vascular function on outcomes in pts with cf-LVADs merits further investigation. Table 1. Comparison Of Vascular Function Testing Between Groups Parameter

Mean Difference

Augmentation Index (AIx) (%) at 75 beats/minute cf-LVAD and HT 18.17 cf-LVAD and HF 12.91 Reactive Hyperemia Index (RHI) cf-LVAD and HT -0.56 cf-LVAD and HF -0.38 Flow Mediated Dilation (FMD) (%) cf-LVAD and HT 0.46 cf-LVAD and HF 1.20

Standard Error

P-value

5.56 5.56

0.006 0.07

0.19 0.19

0.01 0.17

1.32 1.34

1.00 1.00

047 The Impact of Lower Post Operative HMII Pump Speeds and Delayed Warfarin Initiation on Subsequent Gastrointestinal Bleeds Sandra Carey1, Hon Keung Tony Ng1, Danielle Sass2, Gonzalo Gonzalez-Stawinski1, Shelley A. Hall1; 1Baylor Univ Medical Center, Dallas, TX; 2Baylor Univ Medical Center, Dallas, TX Introduction: The current literature for HMII LVAD recipients reports a GI bleed rate of 22%. Current recommendations to reduce GI bleeding are to lower anti-coagulation, but no studies have demonstrated that this intervention successfully reduces GI bleeding rates. We chose to analyze the impact of lowering our prior standard post op pump speed and delaying warfarin initiation. Hypothesis: To review impact of starting with lower HMII LVAD speeds post operatively and delaying warfarin initiation on GI bleeding event rates in our patients. Methods: This was a retrospective, pre-/post-implementation observational study. All patients implanted with a HMII from 06/2008-02/2013 were assessed for post-implant GI bleeding events. Prior to 05/2012, standard process followed in all patients included maintaining a post-operative pump speed of 9200-9600 RPMs and starting warfarin on post-op day 2. In 05/ 2012, standard process was altered. Starting pump speeds were now set at 8400-8800 RPMs and warfarin was initiated upon transfer to telemetry (average POD3). We compared the odds of GI bleeding in patients who underwent implantation after this process change to those patients prior. Results: From 06/2008-02/2012, 128 patients were implanted with a HMII LVAD. The average patient age was 56.9 yrs. Males made up 81.3% of the total patient population (78.8% in pre-process change group and 89.7% in post-process change group). In the pre-process change group. 47.6% of women and 28.2% of men experienced at least one GI bleed, for a total

of 32 GI bleeding events. For those patients, the average number of bleeds was 2.3 (range 1-7). The post-process change group has experienced NO GI bleed. The adjusted (age, sex, length of stay, and days in ICU) analysis carried out with logistic regression model employing a penalized likelihood method revealed increased odd of GI bleed event in the pre-process group (odds Ratio523.4; 95% CI 5 1.5, 376.4). Conclusions: Utilizing lower post-op pump speeds and delaying initiation of warfarin produced a drastic decline in GI bleeding events. Further analysis is warranted to ascertain safety and efficacy of this approach.

048 Clinical Outcomes of Left Ventricular Assist Device Exchange for Suspected Thrombus Geetha Bhat, Antone Tatooles, Colleen Gallagher, Laura Coyle, Patroklos Pappas; Advocate Christ Medical Center, Oak Lawn, IL Introduction: Advanced heart failure patients are being supported with continuous flow (CF) left ventricular assist devices (LVAD) for longer periods of time due to organ shortage for LVAD bridge to transplant patients (pts) and pts undergoing destination therapy (DT). Thromboembolic events can occur both short and long term, and anticoagulation is usually indicated after LVAD implantation. There is minimal data on treatment options and clinical outcome of suspected LVAD thrombus. The optimal therapy for pump thrombus is challenging and thrombus may be addressed by prompt surgical intervention with LVAD exchange. Goal: The goal of our study was to evaluate clinical presentation and outcome of LVAD exchange surgery for suspected thrombus. Methods: Retrospective chart review was performed on 215 consecutive continuous flow LVAD pts. A total of 15 patients (12 male and 3 female with a mean age of 54 6 7 years, 80% DT), 12 HeartMate IIÒ (Thoratec), 3 HeartWareÒ HVAD devices presenting with suspected pump thrombus associated with laboratory findings consistent with hemolysis and 12 of 15 pts undergoing surgical exchange were evaluated. Laboratory values of LDH, plasma hemoglobin (PHgb), haptoglobin, creatinine (Cr), Hemoglobin (Hg), clinical presentation, anticoagulation regimen, 30 day mortality after exchange surgery and mean duration of survival after exchange were analyzed. Results: A total of 15 LVAD pts presented with heart failure symptoms and (14/15) with hematuria at a median of 214 days (15-911) after initial LVAD implant. There were 11 pts who had one exchange and one pt undergoing two exchanges. 30 day mortality after exchange was 1/12 (8%) and mean survival after exchange was 345 days. Two of fifteen pts were not exchanged and expired. One of fifteen patients had suspected thrombus at 19 days after LVAD and underwent medical therapy with intensified anticoagulation and resolution. The patient is currently awaiting transplant. LVAD median speed was 9200 rpm (8600-10,000), median power 7.1 watts (4-24.5). Mean LDH was 2666 6 1000, mean haptoglobin !6, median PHgb 58.5 (14-538), median Cr 1.5 (0.9-6.3), mean Hgb 8.2 6 1.7. All explanted pumps had confirmed thrombus. Conclusion: Prompt surgical explantation and pump exchange for suspected thrombus results in resolution of hemolysis and removal of thrombus with good outcomes and survival. Severe hemolysis due to thrombus which can result in anemia, hematuria, renal dysfunction and severe adverse events of intravascular plasma Hgb can resolve with surgical exchange with no intraoperative mortality, low early mortality, and no adverse effect on late survival. Prospective studies on larger group of LVAD pts may provide early indicators of pump thrombus prior to presentation with multi-organ dysfunction and need for surgical exchange. Further investigation needs to be done on causes of pump thrombus, adequacy of anticoagulation and early diagnosis of thrombus.

049 Recovery of SERCA Protein Following LVAD Support: Heartmate vs Heartmate II Wendy E. Sweet1, Mosi K. Bennett2, Kristen L. Karohl1, Nader Moazami3, Randall C. Starling2, Christine S. Moravec1; 1Cleveland Clinic, Cleveland, OH; 2Cleveland Clinic, Cleveland, OH; 3Cleveland Clinic, Cleveland, OH SERCA (sarocoplasmic endoplasmic reticulum Ca2+ATPase) is a key Ca2+ regulatory protein in the cardiac myocyte, shown to be decreased both at the protein and mRNA levels in failing human hearts. Evidence for this decrease and its role in diminishing contractility of failing human cardiac muscle has been well enough accepted to warrant a clinical trial, testing the hypothesis that adenoviral coupled gene delivery of SERCA is safe and effective in patients with end stage heart failure (the CUPID trial). We have previously reported that depressed SERCA was restored by treatment with a left ventricular assist device (LVAD), and that the reversal of SERCA produced changes in the phospholamban to SERCA ratio and correlated with functional recovery of post-rest potentiation in muscles taken from the same hearts, suggesting normalized sarcoplasmic reticulum function. SERCA reversal was duration-dependent, with the greatest recovery shown in patients supported for 90 days or less. In the previous report, we measured SERCA protein in patients supported prior to transplant by the Heartmate (HM), an older generation pulsatile flow LVAD. We have now tested the hypothesis that the newer, continuous flow LVAD, Heartmate II (HMII), produces the same degree of remodeling following support of the failing heart. Western blot analysis was used to compare protein levels from non-failing (NF), failing (F) and LVAD-supported failing human hearts. The LVAD group was divided between those who had been supported prior to transplant with the HM device and those who had