Continuous-flow Left Ventricular Assist Device Recipients Research Articles

OC30 HEMOCOMPATIBILITY-RELATED ADVERSE EVENTS AND PHYSIOLOGICAL CIRCULATORY INTERFACE OF DIFFERENT GENERATION LEFT VENTRICULAR ASSIST DEVICES

Abstract Background and Aim: Aim of this study has been to assess the rate of hemocompatibility-related adverse events (HRAEs) of current generation centrifugal pumps and older axial continuous-flow (CF) left ventricular assist devices (LVADs). Methods: We identified 193 CF LVAD recipients at three institutions. We studied the quantitative estimates of freedom from HRAEs between 3 types of pumps, the HeartMate II (HMII,n = 56), the HeartMate 3 (HM3,n = 38) and the HeartWare HVAD (HVAD,n = 99). The net burden of HRAE was assessed by using the MOMENTUM 3 hemocompatibility score. Results: Survival free of any HRAE was achieved in 86% of the HM3 group, 64% of the HMII group and 52% in HVAD group (hazard ratio, 0.64; confidence interval, 0.40–0.95; p = 0.014). Using the hemocompatibility score, the HM3 group demonstrated less pump thrombosis requiring reoperation (0 versus 6 and 14 points, for HMII and HVAD, respectively, p = 0.002) or medically managed pump thrombosis (0 versus 4 points and 17 points, for HMII and HVAD, respectively, p = 0.001), and fewer nondisabling strokes (6 versus 14 and 30 points, for HMII and HVAD, respectively, p = 0.002). The net hemocompatibility score in the HM3 in comparison with the HMII and HVAD patients was 71 (0.66 ± 1.45 points/patient) versus 103 (0.86 ± 1.59 points/patient) and 157 (0.96 ± 1.71 points/patient), respectively (odds ratio, 0.66; confidence interval, 0.38–1.01; p = 0.063). Conclusions: In this analysis, HM3 had a more favorable physiological circulatory interface at 36 months in comparison with HMII and HVAD. This confirms the need to develop different clinical monitorings and coagulation management protocols when facing with various device platforms.

Factors Associated With Prolonged Survival in Left Ventricular Assist Device Recipients

Limited data exist on factors predicting prolonged survival in left ventricular assist device (LVAD) recipients. We sought to identify patient characteristics and complications associated with prolonged survival. We conducted retrospective review of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database, including primary continuous-flow LVAD recipients, between May 2012 and March 2013. Patients were identified as having survived with a device in place after 3 years or not, conditional onhaving initially survived 6 months. Patients who received a transplant, underwent explant due to recovery, or were lost to follow-up before 3 years were excluded. Multivariate logistic regression evaluated perioperative factors and adverse events within 6 months associated with long survival. Of 1,116 patients who survived past the initial 6 months, 725 (65%) survived beyond 3 years. On univariate analysis, long-term survivors were significantly younger, were less likely to be white, supported for destination therapy, have diabetes, solid-organ cancer, ortake amiodarone. On multivariate analysis, factors associated with increased odds of death at 3 years included diabetes, amiodarone use, and developing stroke, gastrointestinal bleeding, hemolysis, or pump thrombosis within 6 months of implantation. Preoperative diabetes and amiodarone use were associated with poor long-term survival in LVAD recipients. Development of early complications of stroke, gastrointestinal bleeding, hemolysis, or pump thrombosis was also associated with poor long-term survival. Early diagnosis and treatment of these complications may improve survival in LVAD recipients.

Effect of Preoperative Atrial Fibrillation on Patients with Chronic Heart Failure Who Undergo Long-Term Continuous-Flow LVAD Implantation

Although preoperative atrial fibrillation (AF) is common in patients undergoing continuous-flow left ventricular assist device (CF-LVAD) implantation, how AF affects outcomes remains unclear. We analyzed our single-center experience with CF-LVAD implantation to determine whether preoperative AF was associated with inferior outcomes. From November 2003 through March 2016, 526 patients with chronic heart failure underwent implantation with the HeartMate II (HMII; n = 403) or HeartWare VAD (HVAD; n = 123). We identified 229 patients (165 HMII, 65 HVAD) who had preoperative AF and compared them with non-preoperative AF patients regarding the incidence of postoperative stroke, as well as long-term survival. After implantation, 139 patients had a stroke (78 non-preoperative AF patients [26.2%], 61 preoperative AF patients [26.6%]; p = 0.84). The rate of events per patient-year was 0.19 in non-preoperative AF patients and 0.22 in preoperative AF patients (p = 0.84). Survival was not significantly different between the two groups (p = 0.60). In Cox regression, preoperative AF was not associated with postoperative stroke (odds ratio: 1.13; 95% confidence interval [CI]: 0.74-1.74; p = 0.55) or survival (hazard ratio: 0.93; 95% CI: 0.71-1.25; p = 0.66). We conclude that in CF-LVAD recipients, preoperative AF did not diminish perioperative or long-term survival or increase the risk of postoperative stroke. These findings suggest that performing concomitant AF ablation during CF-LVAD implantation may be unnecessary.

Gastrointestinal Bleeding is Associated with a Shift Towards a Pro-Angiogenic Phenotype after Continuous Flow Left Ventricular Assist Device Implantation

Introduction Gastrointestinal bleeding (GIB) occurs in up to 20% of continuous-flow left ventricular assist device (CF-LVAD) recipients. A higher risk of GIB has been observed in CF-LVAD recipients with lower device pulsatility, yet a mechanism linking changes in hemodynamics to increased GIB is lacking. Hypothesis We hypothesized that 1) levels of Ang-1, a growth factor with vascular protective effects, would be lower while levels of vascular endothelial growth factor A (VEGF-A), an inducer of angiogenesis, and Ang-2, a promoter of vascular destabilization, would be higher in (a) CF-LVAD recipients compared to controls and (b) in CF-LVAD recipients with GIB as compared to those without; and that 2) CF-LVAD pulsatility and pulse pressure would be positively correlated with levels of Ang-1 and negatively correlated with VEGF-A and Ang-2. Methods Twenty-four participants from our institution, 12 with CF-LVADs (6 of whom had GIB after LVAD implantation) and 12 age-matched controls with no history of heart failure or GIB, contributed venous blood samples. We measured VEGF-A, Ang-2, and Ang-1 levels in serum fractions with immunoassays. Results Ang-2 levels were higher and Ang-1 levels lower in CF-LVAD recipients compared to controls with no difference in VEGF-A levels. Ang-1 levels were lower in CF-LVAD recipients with GIB compared to those without; Ang-2 and VEGF-A levels did not differ between the two groups. There was no correlation between pulsatility index and Ang-2, Ang-1, or VEGF-A levels. Pulse pressure was negatively correlated with Ang-2 levels (r = −0.578, P = 0.003), positively correlated with Ang-1 levels (r= 0.496, P = 0.014), and not correlated with VEGF-A levels. Conclusions CF-LVAD recipients demonstrate a shift toward a pro-angiogenic phenotype in the angiopoietin pathway, with increased levels of Ang-2 and lower levels of Ang-1 as compared to controls. Lower levels of Ang-1 were associated with GIB following CF-LVAD implantation. Lastly, lower pulse pressure was associated with higher Ang-2 levels and lower Ang-1 levels. These results suggest a contribution of altered angiogenesis to the observed increased risk of GIB in this population and a potential link to altered hemodynamics.

Sex-Related Differences in Outcomes of Thoracic Organ Transplantation and Mechanical Circulatory Support.

Sex-Related Differences in Outcomes of Thoracic Organ Transplantation and Mechanical Circulatory Support.

Sex-Specific Outcome Disparities in Patients Receiving Continuous-Flow Left Ventricular Assist Devices: A Systematic Review and Meta-analysis.

Continuous-flow left ventricular assist devices (CF-LVADs) decrease mortality and improve quality of life in patients with advanced heart failure (HF). Their widespread utilization has led to concerns regarding increased adverse effects, especially in women. Nevertheless, sex-specific data remain limited. We searched Medline, Embase, Scopus, and the Cochrane Library for publications reporting sex-specific outcomes after CF-LVADs from January 2008 through January 2017. Outcomes were compared under the random-effects model and heterogeneity examined via χ test and I statistics. A total of 10 studies including 4,493 CF-LVAD recipients were included in the analysis (23.5% women). The overall rate of stroke was significantly higher in women (odds ratio [OR] 1.94; 95% confidence interval [CI] 1.32-2.84; p = 0.0007). This was true for ischemic strokes (OR 2.03; 95% CI 1.21-3.42; p = 0.008) and hemorrhagic strokes (OR 2.03; 95% CI 1.21-3.42; p = 0.008). Women were also more likely to develop right HF necessitating right ventricular assist device (RVAD) implantation (OR 2.12; 95% CI 1.08-4.15; p = 0.03). Other adverse events including renal failure, bleeding, and device-related infection were comparable for both genders. The overall mortality while on CF-LVAD was similar in both groups (OR 1.05; 95% CI 0.81-1.36; p = 0.71). Our analysis suggests that women are at greater risk of significant complications such as cerebrovascular events and right HF necessitating RVAD after CF-LVAD implantation. Further research is needed to better understand the mechanisms underlying these sex-specific outcome disparities.

Unrecognized Left Heart Failure in LVAD Recipients: The Role of Routine Invasive Hemodynamic Testing.

The role of routine right heart catheterizations (RHCs) in left ventricular assist device (LVAD) patients is undefined. We analyzed 105 continuous-flow LVAD recipients who underwent an RHC approximately 3 months after implant. In 38 patients, LVAD speed was ramped with the goal of optimizing hemodynamics. Our cohort consisted of 71 (68%) HeartMate II (HMII) and 34 (32%) HeartWare (HVAD) patients. Thirty patients (29%) had either a reduced cardiac index (CI ≤ 2.2 L/min/m), elevated pulmonary capillary wedge pressure (PCWP > 18 mm Hg), or both. A subgroup of 38 patients (19 with abnormal hemodynamics) underwent LVAD ramping. With LVAD ramping, normalization of hemodynamics was achieved in 13 (68%) patients with abnormal hemodynamics. In ramped patients, the CI increased from 2.1 L/min/m (2.0-2.3) to 2.5 L/min/m (2.3-2.6; p = 0.004), and the PCWP dropped from 21 mm Hg (20-26) to 18 mm Hg (14-21, p < 0.001). The 6-minute walk distance improved from 338 m (253-394) to 353 m (320-442, p = 0.041). A 400 rpm change in HMII speed was like a 130 rpm change in HVAD speed and led to a change in cardiac output (CO) of 0.3 L/min. The correlation between device-reported flow and measured CO for both the HMII (Rs = 0.50, p < 0.001) and HVAD (Rs = 0.47, p < 0.001) was moderate. At 3 months after LVAD implant, most patients have normal hemodynamics. Of those patients with abnormal hemodynamics, LVAD ramping results in normalization of hemodynamics and improvement in 6-minute walk distance.

Limited usefulness of endoscopic evaluation in patients with continuous-flow left ventricular assist devices and gastrointestinal bleeding

Gastrointestinalbleeding (GIB) is a frequent cause of re-admission in patients with continuous-flow left ventricular assist devices (CF-LVADs) and is associated with multiple endoscopic procedures and high resource utilization. Our aim was to determine the diagnostic and therapeutic yield of endoscopy and to develop a more cost-effective approach for the management of GIB in CF-LVAD recipients. We retrospectively reviewed 428 patients implanted with a CF-LVAD between 2009 and 2016 at the Columbia University Medical Center and identified those hospitalized for GIB. Patients were categorized into upper GIB (UGIB), lower GIB (LGIB) and occult GIB (OGIB), based on clinical presentation. Eighty-seven CF-LVAD patients underwent a total of 164 GIBs, resulting in 239 endoscopies. Index presentation was consistent with UGIB in 30 (34.5%), LGIB in 19 (21.8%) and OGIB in 38 (43.7%) patients. On the first GIB, 147 endoscopies localized a bleeding source in 49 (30%), resulting in 24 (16.3%) endoscopic interventions. Of 45 lesions identified, arteriovenous malformations (AVMs) were the most common (22, 48.9%). A gastric or small bowel source (HR 2.8, p = 0.003) and an endoscopic intervention (HR 1.9, p = 0.04) predicted recurrent GIB. The proposed algorithm may reduce the number of endoscopic procedures by 45% and costs by 35%. Occult GIB is the most common presentation in CF-LVAD patients and carries the lowest diagnostic and therapeutic yield of endoscopy. Performing an intervention was among the strongest predictors of recurrent GIB. Our proposed algorithm may decrease the number of low-yield procedures and improve resource utilization.

Abstract 20999: Cardiac Implantable Electrical Device Related Procedures and Associated Complications in Continuous Flow LVAD Recipients: A Multicenter Experience

Introduction: Patients with continuous flow Left Ventricular Assist Devices (LVAD) and concomitant Cardiac Implantable Electrical Devices (CIED) are prone for device and lead-related complications requiring intervention. Hypothesis: We evaluated the incidence and characteristics of CIED-related procedures and complications and their association with survival in a multicenter LVAD cohort. Methods: We retrospectively reviewed data on 480 LVAD patients with a CIED from 5 centers. Of the 480, 235 patients had accurate long-term CIED follow-up data and were used for this analysis. Kaplan Meier analysis was used to assess survival differences between patients with CIED-related complications versus those who did not. Results: Of 235 patients with an LVAD and a CIED (Age 58±13, 80% male), 130 had a CRT-D and 105 had ICD only. During a median LVAD follow-up of 692 days, 103 patients required a CIED generator replacement with CRT-D patients having a significantly higher rate of generator replacement compared to the ICD only group (68[52%] vs 35[33%], p=0.003). A CIED or lead-related complication occurred in 36 (28%) of CRT-D patients and 16 (15%) of the ICD patients (p=0.06). 20 (15%) patients in the CRT-D group and 14 (13%) in the ICD group underwent lead removal or extraction during follow-up (p=0.5). Both the CRT-D and ICD groups had comparable incidences of pocket hematoma (8% vs 5%), pocket and/or lead infection (9% vs 4%), and lead malfunction (8% vs 9%). Kaplan Meier analysis showed no significant survival difference between those who had a CIED-related complication versus those who did not (log rank p= 0.7). Conclusions: CIED related procedures are common in LVAD patients. Compared to ICD only, continued CRT-D post-LVAD resulted in a significantly higher number of generator changes and showed a trend towards higher device or lead related complications. CIED-related complications were not associated with reduced survival.

Gastrointestinal Bleeding after Continuous Flow Left Ventricular Assist Device Implantation: Analysis of the INTERMACS Registry

Continuous flow left ventricular assist devices (CF-LVADs) are associated with increased gastrointestinal bleeding (GIB) when compared with pulsatile devices. The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), the national registry of patients with FDA-approved durable devices, was analyzed to characterize GIB in CF-LVAD recipients. Median time from implantation to GIB, frequency of GIB-related rehospitalization, transfusion and death, and risk factors for GIB were determined. Adult patients older than18 years, with primary CF-LVAD implantation between 2006 and 2014, were included. Exclusion criteria were previous or concurrent placement of RVAD or total artificial heart. The primary outcome of interest was incidence of GIB in CF-LVAD recipients. Multivariable Cox proportional hazards model was used to examine associations of GIB with potential risk factors. Of 10,470 patients, 2,717 (26%) experienced GIB, with 1,316 (12.6%) experiencing >1 GIB. Median time to first GIB was 3.1 months (Q1 0.9, Q3 10.2). Rehospitalization occurred in 49.2% of GIB events, with 88.7% requiring transfusion and 0.7% resulting in death. Identified risk factors in multivariable analysis included older age, female sex, ischemic etiology, low pre-operative hemoglobin and elevated creatinine, longer cardiopulmonary bypass time, and lower INR after implantation. The majority of GIB events occur early after CF-LVAD implantation and are primarily associated with older age. Patients in their fifth decade of life have 4.6 times the risk of GIB compared with those in their second decade. Nearly half of patients with GIB experience >1 GIB, and GIB is a significant driver of rehospitalization and transfusion, but rarely results in death.

073_16794-J1 Cardiac Implantable Electrical Device related Procedures and Associated Complications in Continuous flow LVAD Recipients: A Multicenter Experience

Patients with continuous flow Left Ventricular Assist Devices (LVAD) and concomitant Cardiac Implantable Electrical Devices (CIED) are prone for device and lead-related complications requiring intervention. We sought to describe the incidence and characteristics of CIED-related procedures and

Preoperative Prealbumin Level as a Predictor of Outcomes in Patients Who Underwent Left Ventricular Assist Device Implantation

Malnutrition has been associated with an increased risk of morbidity and mortality in patients who undergo cardiac surgery. However, many measurements of malnutrition have been inadequate prognostic markers. In this study, we sought to determine whether low preoperative serum prealbumin level was associated with morbidity and mortality in patients who underwent continuous-flow left ventricular assist device (CF-LVAD) implantation. From November 2003 to March 2016, 526 patients with chronic heart failure underwent implantation of a CF-LVAD (HeartMate II, n = 403; HeartWare HVAD, n = 123). Our cohort comprised the 317 CF-LVAD recipients whose records included the preoperative serum prealbumin level. These patients were divided into 2 groups: those with a normal preoperative serum prealbumin level (>17 g/dL) and those with hypoprealbuminemia (≤17 g/dL). These groups were then compared with regard to preoperative demographics, incidence of postoperative complications, long-term survival rate, and cause of death. Kaplan-Meier survival analysis revealed that patients with a low preoperative prealbumin level had significantly decreased survival rates at 1, 6, 12, and 24 months (p <0.001) after CF-LVAD implantation and higher overall mortality (p = 0.04) than the patients with a normal prealbumin level, and that exacerbated heart failure made up the majority of this difference within the first 6 months. However, we found no significant correlations between low prealbumin level and postoperative complications. In conclusion, our findings demonstrate that preoperative serum prealbumin levels predict patient outcomes after CF-LVAD implantation.

Left ventricular assist device outcomes based on flow configuration and pre-operative left ventricular dimension: An Interagency Registry for Mechanically Assisted Circulatory Support Analysis

Axial configuration (AC) and centrifugal configuration (CC) left ventricular assist devices (LVAD) have different flow characteristics, and whether the interaction between device flow configuration and the pre-operative left ventricular internal diastolic diameter (LVIDD) mediates adverse events after LVAD implantation is unknown. We queried 9,424 continuous-flow LVAD recipients who received LVADs from April 2008 to June of 2015 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). The pre-operative LVIDD * flow configuration interaction term was tested in multivariable models to determine its relationship to adverse events. The pre-operative LVIDD * flow configuration interaction was a significant predictor of device thrombosis. As the LVIDD increased, the risk of AC device thrombosis increased compared with CC devices (p = 0.0099). At 7.0 cm, the hazard ratio (HR) for AC device thrombosis compared with the CC device was 1.61 (95% confidence interval [CI], 1.17-2.22; p = 0.004) and continued to rise as the LVIDD increased. The LVIDD * flow configuration interaction did not predict stroke, gastrointestinal bleeding, or patient survival. In multivariable models, the hazard of stroke was higher with the CC device regardless of the LVIDD (HR, 1.96; 95% CI, 1.64-2.36; p < 0.0001). Adjusted analyses showed LVAD implantation into a larger left ventricle was associated with a lower risk of death (HR, 0.90; 95% CI, 0.85-0.95; p = 0.0004) per centimeter of LVIDD. Our study suggests that the pre-operative LVIDD, flow configuration, and interaction terms should be considered individually when choosing the appropriate LVAD to mitigate the rates of device thrombosis, stroke, and death.

Does Small Size Matter With Continuous Flow Devices?: Analysis of the INTERMACS Database of Adults With BSA ≤1.5 m2

ObjectivesThis study investigated how small patient size affects clinical outcomes in patients implanted with a continuous flow left ventricular assist device (CFLVAD). BackgroundThe development of smaller CFLVADs has allowed ventricular assist device (VAD) use in anatomically smaller patients; however, limited outcome data exist regarding CFLVAD use in patients with a body surface area (BSA) ≤1.5 m2. MethodsAll CFLVAD patients entered in the Interagency Registry for Mechanically Assisted Circulatory Support registry April 2008 to September 2013 and with BSA data were included. Biventricular VAD patients were excluded. Patient characteristics and clinical outcomes were compared between patients with BSA ≤1.5 m2 (small patients) and those >1.5 m2. ResultsOf 10,813 CFLVAD recipients, 231 had a BSA ≤1.5 m2. Small patients were more commonly female patients (68% vs. 20%; p < 0.01), Hispanic (10% vs. 6%; p < 0.03), and on intravenous inotropes (88% vs. 80%; p < 0.01). Small patients had higher bleeding (p < 0.01) and driveline infection (p < 0.01) rates, while exhibiting lower rates of right heart failure (p < 0.01) and renal dysfunction (p < 0.01). Device malfunction rate (p > 0.05), overall survival (p > 0.05), and 1-year competing outcomes (p > 0.05) were similar between BSA groups. ConclusionsPatients with a BSA ≤1.5 m2 supported with a CFLVAD have similar survival to larger patients. These data support the use of CFLVAD in anatomically small patients.

Ventricular Assist Device Therapy in Older Patients With Heart Failure: Characteristics and Outcomes

BackgroundLimited data exist on outcomes in patients ≥70 years of age supported with the use of continuous-flow left ventricular assist devices (LVADs). MethodsData on 1149 continuous-flow LVAD recipients was queried from the Mechanical Circulatory Support Research Network. Groups were assigned based on age: ≥70 years (“older patients”) and <70 years. The primary outcome was survival at one-year based on age grouping. ResultsCompared with younger patients (54.3 ± 11.2 y; n = 986), older patients (73.4 ± 3.0 y) constituted only 14% of LVAD implants. Older patients had similar rates of device thrombosis (P = .47) and stroke (P = .44), but survival-free of gastrointestinal bleeding (GIB) at 1 year was lower compared with younger patients (58% vs 69%; P < .01). Unadjusted survival at 1 year in older patients was 75% compared with 84% in younger patients, and at 2 years 65% versus 73% (P = .18). Age ≥70 years was not associated with increased mortality (adjusted hazard ratio [aHR] 0.94, 95% confidence interval [CI] 0.70–1.26; P = .67). Preoperative creatinine (aHR 1.57, 95% CI: 1.30–1.89, P < .0001), bilirubin (aHR 1.22, 95% CI 1.05–1.42; P = .010), and ischemic cardiomyopathy (aHR 1.43, 95% CI 1.11–1.84; P = .005) portended increased risk of death. In older patients, the only predictor of mortality was creatinine (HR 2.1, 95% CI 1.2–3.4; P = .007). Creatinine ≥1.4 mg/dL was associated with a 1-year survival of 65%, compared with 84% when the creatinine was <1.4 mg/dL (P = .009). ConclusionAge >70 years is an important consideration when assessing LVAD risk, but other correlates may be more predictive of LVAD survival. Older patients without renal dysfunction have survival similar to younger patients. Older patients should be counseled about age-correlated risks, including higher rates of GIB.

Recovery of Serum Cholesterol Predicts Survival After Left Ventricular Assist Device Implantation.

Advanced systolic heart failure is associated with myocardial and systemic metabolic abnormalities, including low levels of total cholesterol and low-density lipoprotein. Low cholesterol and low-density lipoprotein have been associated with greater mortality in heart failure. Implantation of a left ventricular assist device (LVAD) reverses some of the metabolic derangements of advanced heart failure. A cohort was retrospectively assembled from 2 high-volume implantation centers, totaling 295 continuous-flow LVAD recipients with ≥2 cholesterol values available. The cohort was predominantly bridge-to-transplantation (67%), with median age of 59 years and 49% ischemic heart failure cause. Total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels all significantly increased after LVAD implantation (median values from implantation to 3 months post implantation 125-150 mg/dL, 67-85 mg/dL, 32-42 mg/dL, and 97-126 mg/dL, respectively). On Cox proportional hazards modeling, patients achieving recovery of total cholesterol levels, defined as a median or greater change from pre implantation to 3 months post-LVAD implantation, had significantly better unadjusted survival (hazard ratio, 0.445; 95% confidence interval, 0.212-0.932) and adjusted survival (hazard ratio, 0.241; 95% confidence interval, 0.092-0.628) than those without cholesterol recovery after LVAD implantation. The continuous variable of total cholesterol at 3 months post implantation and the cholesterol increase from pre implantation to 3 months were also both significantly associated with survival during LVAD support. Initiation of continuous-flow LVAD support was associated with significant recovery of all 4 lipid variables. Patients with a greater increase in total cholesterol by 3 months post implantation had superior survival during LVAD support.

Aortic insufficiency in continuous-flow left ventricular assist device support patients is common but does not impact long-term mortality

Aortic insufficiency (AI) is a significant long-term complication of continuous-flow left ventricular assist device (CF-LVAD) implantation. We sought to evaluate its impact on clinical outcomes and mortality in CF-LVAD recipients. We retrospectively analyzed 237 patients implanted with HeartMate II CF-LVADs at our institution from June 2005 through June 2013. We evaluated recipients' baseline characteristics and annual echocardiograms, grading AI severity as either none, trace, mild, moderate or severe. Only moderate or severe AI was considered clinically significant. Recipients who underwent concomitant aortic valve surgery or who had undergone previous prosthetic aortic valve implantation were excluded. Moderate or severe AI occurred in 32 (15.2%) patients. Risk factors that significantly affected the development of AI included older age at the time of implantation, female gender, longer duration of LVAD support and destination therapy designation. Freedom from moderate or severe AI was 94%, 76% and 65% of patients at 1, 3 and 5 years, respectively. Overall cohort survival based on Kaplan-Meier analysis was 78%, 59% and 42% at 1, 3 and 5 years, respectively. There was no difference in survival between recipients who developed significant AI and those who did not (log-rank test, p = 0.73). In this large, single-institution study, the overall rate of AI was low, but increased in frequency with longer duration of LVAD support. Although AI development remains a concern for patients on long-term CF-LVAD support, AI development does not appear to impact long-term mortality.

Abstract 13556: Elderly Patients Receiving Durable LVAD Support: Insights and Outcomes

Introduction: Age ≥ 70 is used to exclude patients from cardiac transplantation. Elderly patients may be offered left ventricular assist device (LVAD) therapy as an alternative. It remains poorly defined how they respond to LVAD support. Hypothesis: Elderly patients have LVAD outcomes that are non-inferior to younger patients. Methods: Data on 1,149 continuous-flow LVAD recipients from May 2004 to May 2015 was pooled from the Mechanical Circulatory Support Research Network (MCSRN). Groups were assigned based on Age ≥ 70 (n = 163) and &lt; 70 (n = 986). Results: Patients age ≥ 70 were more likely to be male (91%), have an ischemic cardiomyopathy (71%), atrial fibrillation (41%), hypertension (66%), diabetes (38%) and prior sternotomy (45%). Older patients also had a lower BMI and higher creatinine, 26.7 ± 0.4 v. 29.9 ± 0.5 and 1.46 ± 0.04 v. 1.35 ± 0.02, p &lt; 0.05. The hazard ratio for mortality was highest in elderly patients in the early post-operative period and stabilized over time with no long-term differences in survival, p = 0.18, Figure 1a. Elderly patients had equivalent rates of device thrombosis and stroke, p = 0.47 and 0.44, Figures 1b-c. Survival free of gastrointestinal bleeding (GIB) at 1-year was 58% in elderly patients compared to 69% in younger patients, Figure 1d, p &lt; 0.01. Multivariate cox regression revealed that age ≥ 70 was not a significant predictor of mortality (HR 0.93, 95% CI 0.69 - 1.25, p = 0.62), but pre-operative creatinine (HR 1.54, 95% CI 1.28 - 1.86, p &lt; 0.01) and bilirubin (HR 1.2, 95% CI 1.03 - 1.4, p = 0.02) were. When age was considered a continuous variable, the HR was 1.2 (95% CI 1.07 - 1.3 per 10y, p &lt; 0.01). Conclusions: Elderly patients, age ≥ 70, have equivalent long-term survival after LVAD implantation with similar rates of device thrombosis and stroke. Rates of GIB were higher in the elderly and this finding warrants caution when choosing anti-coagulation protocols in the elderly. Overall age ≥ 70 does not portend a poorer survival after LVAD implant.

Abstract 18299: Device Selection: Does Ventricular Size Matter in LVAD Recipients?

Introduction: Axial and centrifugal-flow left ventricular assist devices (LVAD) have varied response to changes in loading conditions. Whether ventricular size modulates the response to LVAD therapy between the axial flow Heartmate II (HMII) and centrifugal flow Heartware (HVAD) is unknown. Hypothesis: Adverse event and survival rates between devices are affected by recipient pre-op left ventricular end-diastolic diameter (LVEDD). Methods: Data on 1,149 continuous-flow LVAD recipients from May 2004 to May 2015 was pooled from the Mechanical Circulatory Support Research Network (MCSRN). The effect of pre-op LVEDD on the instantaneous hazard of death and adverse events was evaluated between HMII (n=864) and HVAD (n=283). Results: The average LVEDD was 7.0cm and did not differ between the device recipients. Patients with a smaller LVEDD (≤ 6.3cm) were more likely female 39% v. 24% (p &lt; 0.0001) and to have an ischemic cardiomyopathy (30% v. 24%, p = 0.045). For every 1cm increase in pre-op LVEDD, the adjusted hazard ratio (HR) for mortality increased with HVAD (HR 1.31, 95% CI 0.94-1.82, p = 0.005) and decreased with HMII (HR 0.78, 95% CI 0.67-0.92, p = 0.005), Figure 1a. Other predictors of mortality included age (HR 1.31, 95% CI 1.12 - 1.53 per 10y, p &lt; 0.001) and bilirubin (HR 1.15, 95% CI 0.94-1.42 per mg/dL, p = 0.027). LVEDD by device type interaction was not a significant predictor of gastrointestinal bleeding or pump thrombosis. The risk of stroke increased with LVEDD for HVAD and decreased for HMII, but this did not reach statistical significance, Figure 1b. Ischemic etiology of heart failure (HR 1.7 95% CI 1.14 - 2.55, p = 0.01) and HVAD device use (HR 1.47 95% CI 1.00 - 2.17, p = 0.03) were significant predictors of stroke. Conclusions: Our data suggest important differences exist in patient outcomes between HMII and HVAD based on pre-op ventricular size. Studies are needed to determine if these differences in outcome are due to device or flow-specific differences in patient support.

Increased cyclic guanosine monophosphate levels and continuous-flow left-ventricular assist devices: Implications for gastrointestinal bleeding

ObjectivesWe examine the hypothesis that cyclic guanosine monophosphate (cGMP) levels are elevated in recipients of continuous-flow left ventricular assist devices (CF-LVADs) and that elevated cGMP levels are associated with a risk of gastrointestinal (GI) bleeding events. MethodsThe levels of cGMP, nitric oxide, platelet activation markers, platelet-derived growth factors (PDGF) AB/BB and AA, and the inflammatory mediator C-reactive protein (CRP) were examined in 19 CF-LVAD recipients, 21 patients who had heart failure, and 19 healthy control-group participants. ResultsThe median level of cGMP was significantly higher in CF-LVAD recipients, compared with healthy participants (6.6 vs 2.1 pmol/mL, u = 62.5; P = .001; r = −0.55). Median cGMP levels in the heart failure group (12.5 pmol/L) were higher, compared with both CF-LVAD recipients (u = 75.0; P = .001; r = −0.53) and healthy participants (u = 4.0; P < .001; r = −0.83). Compared with the healthy group, median CRP levels were significantly higher in CF-LVAD recipients (2.9 vs 8.0 mg/L; u = 58.0; P < .001; r = −0.63) and heart failure patients (2.9 vs 7.0 mg/L; u = 59.0; P < .001; r = −0.65). In the subgroup of patients supported with the HeartMate II (Thoratec Corporation, Pleasanton, Calif), pulsatility index was significantly negatively correlated with cGMP levels (r = −0.73; P < .05), indicating that low pulsatility index is associated with higher cGMP levels. High cGMP levels were significantly associated with GI bleeding events, but not with bleeding events in general. ConclusionsThe primary finding of this study is that GI bleeding in CF-LVAD recipients is associated with significantly elevated cGMP levels, despite high levels of CRP, which interfere with cGMP production. Further studies are required to determine whether elevated cGMP levels can be used as a clinical marker for increased risk of GI bleeding in CF-LVAD recipients.