Continuous-flow Left Ventricular Assist Devices Patients Research Articles

Effects of Continuous-Flow Left Ventricular Assist Device Therapy on Peripheral Vascular Function

The peripheral vascular effects of continuous-flow left ventricular assist device (CF-LVAD) implantation are still unclear. The aim of the current study was to determine peripheral vascular function before and after implantation of CF-LVAD in patients with end-stage heart failure (HF), and to compare this data to age- and sex-matched chronic heart failure with reduced ejection fraction (HFrEF) patients. Forty-three consecutive end-stage HF patients (New York Heart Association [NYHA] class III/IV; three women and 40 men; mean age 53 ± 11 years) who planned to receive CF-LVAD implantation comprised the LVAD patient population, and their clinical characteristics, preoperative and third postoperative month peripheral vascular function assessment data including flow-mediated dilation (FMD) and pulsatility index (PI) assessed by ultrasound Doppler in brachial artery were compared to age- and sex-matched chronic, stable HFrEF patients (NYHA class II; five women and 30 men; mean age 51 ± 10 years). After CF-LVAD implantation, median FMD decreased from 5.4 to 3.7% (p < 0.001), and median PI decreased from 6.9 to 1.4 (p < 0.001). In patients with end-stage HF before CF-LVAD implantation, FMD and PI were significantly lower compared to the chronic HFrEF patients (FMD: 5.4% ± 0.9% vs. 7.6% ± 1.1%; p < 0.001, respectively) and (PI: 6.9 ± 1.3 vs. 7.4 ± 1.2; p = 0.023, respectively). The current study revealed impaired peripheral vascular function in the end-stage HF patients compared to stable HFrEF patients, and documented the deterioration of peripheral vascular function after CF-LVAD implantation. These results suggest that impaired peripheral vascular function in the CF-LVAD patients compared to preoperative assessment is a consequence of the nonpulsatile blood flow due to the continuous-flow mechanical support.

Development of malignancies and their outcomes in patients supported on continuous-flow left ventricular assist devices-a systematic review.

With increased use of continuous-flow left ventricular assist devices (CF-LVAD), development of malignant tumors in this population is not uncommon. We sought to evaluate malignancies in CF-LVAD patients and evaluate the outcomes of treatment strategies. Overall, 18 articles consisting of 28 patients were identified who developed malignancies after CF-LVAD placement. Patient-level data were extracted for systematic review. Median patient age was 60 years [59-67] and 85.7% (24/28) were male. CF-LVAD was placed as bridge-to-transplant (BTT) in 60.9% (14/23) of patients. The three most common malignancy types were GI in 35.7% (10/28) of patients, lung in 21.4% (6/28) and skin in 10.7% (3/28). Median time from CF-LVAD implant to malignancy diagnosis was 6.9 [2.5-12.8] months. Metastatic disease occurred in 17.9% (5/28) over a median time of 5.0 [1.0-82.0] months from the diagnosis. Surgical resection of the malignancy was performed in 57.1% (16/28) of patients. Our results showed that while there was a significantly higher probability of survival among patients who underwent surgery versus those who did not, when only stage I and II patients were included in the analysis, this difference was no longer statistically significant. Three patients were relisted for heart transplant after surgical treatment, and two received the transplant. Surgical management of malignancies in patients on CF-LVADs may improve survival and transplant eligibility status, therefore, a CF-LVAD should not always preclude surgical treatment.

Multicenter Italian Study on Radial Mechanically Assisted Circulatory Support (MIRAMACS): Preliminary Results

Purpose The Multicenter Italian study on RAdial Mechanically Assisted Circulatory Support (MIRAMACS) represent the first national observational registry, gathering continuous-flow (CF) left ventricular (LVAD) and biventricular assist device (BiVAD) implantation performed in adult patients by high-volume, mechanical circulatory support (MCS) dedicated, Italian centres. Methods Seven participating hospitals contributed pre-, peri- and long-term postoperative data on LVAD implants to the registry. Data for all implants in adult patients (>18 years of age) performed between January 2000 to September 2020 were analysed. BiVADs were excluded in this preliminary analysis. This initial report focuses on patient demographics, survival, device types, adverse events and competing outcomes. Results A total of 515 patients received a CF LVAD. The mean age of LVAD recipients was 60±10 years. The majority of patients were male (89.3%). The adopted systems were: HeartWare HVAD (n=213), HeartMate III (n=140), HeartMate II (n=89), Jarvik 2000 (n=50), Berlin Heart Incor (n=19) and other brands (n=4). In 6.6% of patients the LVAD implantation was performed by usage of less invasive surgical approaches. Mortality at 30- and 90-days was 6.1% and 11.1%, respectively. A temporary right ventricular assist device (RVAD) support was necessary in 3.1% of patients. Mean follow-up time was 57±15 months. Heart transplantation was performed in 99 patients (19.2%). Survival at 1-year, 3-years, and 5-years of BTT cohort was 82.1%, 60.4% and 41.8%, respectively. Survival at 1-year, 3-years, and 5-years of DT cohort was 69.8%, 45.6% and 30.1%, respectively. Major bleeding, major infection, neurological events and device malfunction were reported in 40 (7.7%), 143 (27.7%), 97 (18.8%) and 36 (6.9%) patients, respectively. Conclusion This first MIRAMACS report reveals frequencies and results comparable with other registries. Overall success rate of CF LVAD patients seems to be satisfactory. Detailed prospective data collection, additional participating centres and further analyses may provide additional robust scientific contributions.

Role of implantable cardioverter-defibrillator in patients awaiting heart transplant in the continuous-flow left ventricular assist device era.

Implantable cardioverter-defibrillators (ICDs) have been shown to have survival advantage in advanced heart failure patients. Few studies have evaluated the role of ICDs in patients supported with continuous-flow left ventricular assist devices (CFVADs). We aimed to evaluate the impact of ICD and CFVAD on heart transplant (HTx) waiting list survival. We queried the United Network for Organ Sharing (UNOS) thoracic transplant database between years 2007 and 2016 for patients aged ≥ 18 years listed for HTx. Patients receiving devices other than CFVAD were excluded. Patients were divided into groups-with and without CFVAD and further subdivided into groups-with and without ICD use. Kaplan-Meier curves were used to evaluate the survival outcomes. There were 34860 patients listed for HTx during study period of which 11481 (32%) had a CFVAD and 26139 (75%) had an ICD. Within CFVAD group, patients with ICD were older, more likely male, with higher creatinine and listed as UNOS status 1A. In the No-CFVAD group, 1-year waitlist survival was significantly better with ICD use (81% vs. 73%, P < .0001); however, in CFVAD patients, 1-year survival with ICD use was comparable to No-ICD use (95% vs. 94%, P = .1). Use of ICD is associated with significantly better heart transplant waitlist survival in patients not supported by CFVAD. In patients supported with CFVAD, the ICD does not offer additional survival benefit.

Endothelial Dysfunction-related Neurological Bleeds with Continuous Flow-Left Ventricular Assist Devices Measured by Digital Thermal Monitor.

Endothelial dysfunction has been demonstrated in patients with Continuous Flow-Left Ventricular Assist Devices (CF-LVADs) but association with adverse events has not been shown. We used a noninvasive, operator-independent device called VENDYS® to assess vasodilatory function based on digital thermal measurements postrelease of a brachial artery occlusion in ambulatory patients with CF-LVAD (n = 56). Aortic valve opening and pulse perception were also documented before the test. Median duration of CF-LVAD support was 438 days. The VENDYS® test generates a vascular reactivity index (VRI). Outcomes for the CF-LVAD patients were compared between VRI < 1 and VRI ≥ 1. The bleeding events were driven primarily by a difference in neurologic bleeds. Multivariate analysis showed that VRI < 1 correlated with future bleeding events (HR: 5.56; P = 0.01). The C-statistic with the VRI dichotomized as above was 0.82. There was a trend toward a worse survival in patients with poor endothelial function. Endothelial vasodilatory dysfunction measured by a simple test utilizing digital thermal monitoring can predict adverse bleeding events in patients with CF-LVADs.

S0608 Prevalence of Gastrointestinal Bleeding in Continuous-Flow Left Ventricular Assisted Device Recipients: An Updated Systematic Review and Meta-Analysis

INTRODUCTION: The use of continuous-flow left ventricular assist device (CF-LVAD) therapy continues to rise as a treatment modality for patients with advanced heart failure. Patients with CF-LVAD are at increased risk of gastrointestinal bleeding (GIB) often requiring recurrent hospitalizations. Approximately one-third of hospital readmissions after LVAD placement are due to GIB. The aim of this study is to assess the prevalence of GIB and recurrent GIB in patients with CF-LVAD by a systematic review and meta-analysis. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to November 2019. Included studies were cohort (prospective or retrospective), case-control, or cross-sectional studies reporting the prevalence of GIB in CF-LVAD patient. Data from each study were combined using the random-effects model. RESULTS: Twenty-three studies from 2009 to 2019 were included in this meta-analysis involving 2,980 CF-LVAD patients. The prevalence of GIB ranged from 15.4% to 39.3% (pooled prevalence = 23.8%, 95% confidence interval: 21.0-26.5, I2 = 65.9%) (Figure 1). Eleven studies reported prevalence of recurrent GIB. The prevalence of recurrent GIB ranged from 4.5% to 17.6% (pooled prevalence = 9.5%, 95% confidence interval: 6.5-12.5, I2 = 63.7%) (Figure 2). There was no publication bias observed in Funnel plot as well as no small study effect observed in Egger’s test. CONCLUSION: This study demonstrates that CF-LVAD patients are at significant risk of both isolated and recurrent GIB. The underlying cause of CF-LVAD associated GIB is multifactorial including abnormal angiogenesis and acquired von Willebrand syndrome. These patients require antiplatelet and antithrombotic therapy further increasing their bleeding risk. Currently the only definitive treatment is heart transplant. Other strategies for primary and secondary prevention of GIB in patient with CF-LVAD continue to be investigated. It is important for clinicians to understand the prevalence of GIB in order to appropriately discuss risks with patients prior to receiving CF-LVAD.Figure 1.: Forrest plot demonstrating the prevalence of GIB in CF-LVAD patients *GIB = Gastrointestinal Bleeding; CF-LVAD = Continuous-Flow Left Ventricular Assisted Device.Figure 2.: Forrest plot demonstrating the prevalence of recurrent GIB in CF-LVAD patients. *GIB = Gatsrointestinal Bleeding; CF-LVAD = Continuous-Flow Left Ventricular Assisted Device.

Cardiopulmonary Exercise Metrics Demonstrate that CF-LVAD Patients Suffer from Residual Heart Failure

Background Continuous flow left ventricular assist devices (CF-LVADs) improve survival and quality-of-life for patients with heart failure with reduced ejection fraction (HFrEF), but exercise capacity remains reduced. While resting and exertional cardiovascular performance is described in the setting of CF-LVAD support, data on pulmonary performance are limited. The primary objective of this study was to describe changes in metrics of cardiopulmonary performance during exercise among HFrEF patients before and after CF-LVAD implantation. Methods 11 HFrEF patients completed submaximal and symptom-limited cardiopulmonary exercise testing (CPET) on three separate visits. Visit 1 involved CPET testing ∼2-4 weeks prior to CF-LVAD implantation. Visit 2 involved CPET testing ∼3 months post-LVAD at a constant pump speed. Visit 3 involved CPET testing ∼4-5 months post-LVAD with progressive increases in LVAD pump speed during exercise. Exercise involved two levels of submaximal exercise below the ventilatory threshold (steady-states 1-2) and peak exercise on an upright cycle ergometer. Breath-by-breath gas exchange parameters (oxygen uptake [VO2], carbon dioxide production [VCO2], minute ventilation [VE]) were recorded by indirect calorimetry. Results Clinical characteristics are summarized in table 1. There was no improvement in submaximal or peak VO2 following LVAD implantation (figure 1) regardless of whether individuals exercised at constant speed (visit 2) or exercised with progressive pump speed increases (visit 3). Ventilatory efficiency improved modestly on visits 2 and 3, but remained severely impaired. Oxygen uptake efficiency slope (OUES) was largely unchanged post-LVAD. Changes in end-tidal carbon dioxide during exercise were similar on all three visits. Conclusions HFrEF patients suffer from severe impairments in functional capacity as measured by oxygen uptake following CF-LVAD implantation, which does not improve with modulations in pump speed. CF-LVAD patients also suffer from severe impairments in ventilatory efficiency. These data suggest that CF-LVAD patients suffer from residual heart failure that is precipitated by submaximal exercise and not alleviated by modulations in pump speed.

Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA)

BackgroundGeographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown. MethodsWe created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months. ResultsThe cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU. ConclusionsAlthough waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.

Factor Xa inhibitors in patients with continuous-flow left ventricular assist devices.

Warfarin is standard anticoagulation therapy for patients with a continuous-flow left ventricular assist device (CF-LVAD). However, warfarin requires regular monitoring and dosage adjustments and fails for many patients, causing thromboembolic and bleeding events. Factor Xa inhibitors have been shown to be noninferior to warfarin in preventing strokes and are associated with less intracranial hemorrhage in patients with atrial fibrillation. We evaluated treatment safety and effectiveness in CF-LVAD patients who switched from warfarin to a factor Xa inhibitor (apixaban or rivaroxaban) after warfarin failure. This was a retrospective, single-center study of patients treated between 2008 and 2018. We assessed the occurrence of stroke, non-central nervous system (CNS) embolism, pump thrombosis, and major gastrointestinal bleeding and intracranial hemorrhage during therapy. We identified seven patients: five were male, the average body mass index was 30kg/m2, and average age was 56years. Preimplantation comorbidities included hypertension (all patients) and diabetes mellitus, ischemic cardiomyopathy, atrial fibrillation, and previous myocardial infarction (fourpatients each). Overall, patients received warfarin for 3968days and apixaban/rivaroxaban for 1459days. The warfarin group was within the therapeutic INR range (2.0-3.0) 30% of the time. Complication rates did not differ between warfarin and apixaban/rivaroxaban: strokes, 0.20 vs none, non-CNS embolism, 0.54 vs none; pump thrombosis, 0.27 vs none; major gastrointestinal bleeding, 0.20 vs 0.50; intracranial hemorrhage, 0.13 vs none. Factor Xa inhibitors may be viable treatment options for CF-LVAD patients for whom warfarin therapy has failed. Large prospective studies are necessary to confirm these results.

Continuous-flow left ventricular assist device implantation in patients with preexisting mechanical mitral valves: a systematic review

ABSTRACTIntroduction: A preexisting mechanical mitral valve (MMV) is thought to be a thrombogenic risk factor after continuous-flow left ventricular assist device (CF-LVAD) implantation. We sought to evaluate the management and outcomes of preexisting MMVs in patients following CF-LVAD implantation.Areas covered: An electronic search was performed to identify the presence of an MMV at the time of CF-LVAD implantation. Of the 1,168 studies identified, only five studies consisting of seven CF-LVAD patients met the inclusion criteria. Patient-level data were extracted and analyzed.Expert opinion: The median patient age was 54 (IQR: 42–61) years and 71.4% (5/7) were male. Non-ischemic cardiomyopathy was the predominant etiology (83.3%, 5/6) of heart failure, and bridge-to-transplant the predominant indication (85.7%, 6/7) for CF-LVAD. Aortic valve prosthesis was present in 42.9% (3/7) of patients. Median time from MMV to CF-LVAD placement was 6.0 years (IQR: 1.3–15.0). The median lower limit of the INR range was 2.8 (IQR: 2.1–3.0) and upper limit of the INR range was 3.5 (IQR: 3.1–3.5). During a median follow-up time of 120 (IQR: 70–201) days, there were no major GI bleeds or clinically significant thromboembolic complications. With adequate anticoagulation, preexisting MMVs in CF-LVAD patients did not result in clinically significant thromboembolic events.

The determinants of functional capacity in left ventricular assist device patients: many actors with not well defined roles.

: Improvement in hemodynamic parameters is routinely demonstrated in patients implanted with continuous-flow left ventricular assist devices (CF-LVADs). However, functional capacity assessed by cardiopulmonary exercise test (CPET), following LVAD implantation, remains considerably restricted. In this review, we analyzed the current knowledge on the causes of the persistent limitation in exercise capacity in CF-LVAD patients. Limitation to exercise is multifactorial and involves: LVAD factors (fixed CF-LVAD pump speed), native cardiac factors (residual function of native left ventricle, right ventricular dysfunction, aortic valve abnormalities), comorbidities (abnormal skeletal muscle metabolism, low skeletal muscle mass, anemia), patient's characteristics (age, physical deconditioning). In addition, we emphasize the role of some potential therapeutic strategies like the increase in CF-LVAD pump speed according to the patient's activity, the echo-optimization of the device (paying attention to right ventricular function and aortic valve opening), the implementation of physical rehabilitation and the treatment of potentially reversible extracardiac factors (anemia, muscle deconditioning, obesity).

Effect of Socioeconomic Status on Patients Supported with Contemporary Left Ventricular Assist Devices

Continuous-flow left ventricular assist devices (CF-LVADs) are increasingly used in advanced heart failure patients. Recent studies suggest that low socioeconomic status (SES) predicts worst survival after heart transplantation. Both individual-level and neighborhood-level SES (nSES) have been linked to cardiovascular health; however, the impact of SES in CF-LVAD patients remains unknown. We hypothesized that SES is a major determinant of CF-LVAD candidacy and postimplantation outcomes. A retrospective chart review was conducted on 362 patients between February 2009 and May 2016. Neighborhood-level SES was measured using the American Community Survey data and the Agency for Healthcare Research and Quality SES index score. Individual-level SES was self reported. Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression determined survival statistics. Patients in the highest SES tertile were older (58 ± 13 vs. 53 ± 14; p < 0.001), less likely to be black or Hispanic (26% vs. 70%; p < 0.001), more likely to be married (87% vs. 65%; p < 0.001), more likely to have private insurance (50% vs. 39%; p < 0.001), and more likely to have employment (29% vs. 15%; p < 0.001) compared with patients in the lowest tertile. Low nSES was associated with a decreased risk of death (hazard ratio [HR], 0.580; 95% confidence interval [CI], 0.347-0.970; p = 0.038) in comparison to the high nSES. However, after adjusting for baseline clinical morbidities, the relationship was no longer present. When selecting patients for a LVAD, SES should not be thought of as an immutable risk factor. Carefully selected low-SES patients could be safely implanted with CF-LVAD with outcomes comparable to high-SES patients.

Increased Platelet Glycoprotein IIb/IIIa Activation Precedes Continuous-Flow Left Ventricular Assist Device Pump Thrombosis Events

Continuous-flow left ventricular assist devices (CFLVAD) in management of end-stage heart failure continues to expand. Adverse events however remain high. Better understanding of platelet activation in the context of CFLVAD therapy may help reduce bleeding and pump thrombosis (PT) risks to patients. Whole blood was collected 15 days post CFLVAD implant. Blood samples were stimulated, stained with anti- CD61, gpIIb/IIIa complex (PAC-1), CD62P, fixed, and analyzed by flow cytometry. Unstimulated blood +/- RDGS were prepared as controls. Platelets were gated as CD61+ and CD62P and PAC-1 signal determined activation. Adverse events (PT/bleeding) were determined through INTERMACS. Median age was 62 years, 21% female, 17 implanted with centrifugal and 2axial flow pumps. Groups consisted of those without an adverse event (No event, n=11), PT (w or w/o bleed, n=3), and Bleeding event only (n=5). Healthy volunteers (n=5) were recruited to serve as controls. CFLVAD implantation alone did not increase PAC-1 platelet activation in patients 15 days post implant. In addition, CFLVAD implantation did not prevent platelets from becoming activated following stimulation. In patients with PT, PAC-1 was higher in unstimulated blood (9.9%) when compared to No event (2.22% p=0.023) and healthy controls (0.66% p=0.028). This elevation of PAC-1 was detected before the clinical manifestation of pump thrombosis (8, 139, 274 days). In addition, following stimulation, PAC-1 was increased significantly in PT patients (89.6%) compared to both No event (54.8% p<0.001) and Bleeding event (60.2% p=0.011) groups. Platelet gpIIb/IIIa activation from PT patients was evident prior to thrombus development. PT patients even had the largest response to stimulation. This increase in platelet activation could serve as a predictor of device-related thrombosis events and may have important implications in targeted therapy to reduce PT in CFLVAD patients.

Physiologically Significant Pulsatility Key to Reducing Adverse Events in CF LVADS

Hypertension is common in continuous flow LVAD (CFLVAD) patients and is linked to major adverse events like stroke and aortic incompetence. The human circulation was modelled with wave propagation and reflections using physiologic data from ADAN 86, with a set of 86 arteries including the cerebral vessels. 1. Blood pressure was compared for a flow of 5 litres/minute for a normal pulsatile flow and CF LVAD with varying degrees of pulsatility RESULTS: CONCLUSION: Restoring physiologically significant pulsatility is likely to restore normal blood pressure with significant reduction in adverse events like stroke, aortic incompetence and gastric bleeds. The degree of pulsatility needed to achieve this needs further study.

Risk Factors for Renal Failure after Continuous-Flow Left Ventricular Assist Device Implantation

Renal failure after continuous-flow Left ventricular assist device (CF-LVAD) implantation increases the risk of death. Although CF-LVAD improve hemodynamic status and affect renal function, there was no study which analyzed the relationship of hemodynamics and renal function after CF-LVAD implantation. Then, we investigated that risk factors for renal failure (RF) in the chronic phase after CF-LVAD implantation using postoperative hemodynamic data. Between October 2005 and August 2018, 191 consecutive patients underwent CF-LVAD implantation at Osaka University Hospital. Of these, 76 who recorded postoperative right heart catheterization were included (mean age, 42 ± 13 years; 38% were women). We used 5 different types of CF-LVADs (HeartMate II: 50%, DuraHeart:13%, Jarvik2000:13%, EVAHEART:16%, HeartWare:8%. Preoperative and postoperative RF was defined that estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m2 at preoperative and postoperative 1 year, respectively. We analyzed the course of renal function after CF-LVAD implantation and the risk factors for RF in the chronic phase. Two weeks after implantation, the mean eGFR was improved from 70 (47-90) to 101 (73-131) mL/min/1.73 m2. However, the renal function showed gradual decline and eGFR was 70 (60-93) mL/min/1.73 m2 at postoperative 1year. There were 17(22%) patients who developed RF at postoperative 1year. Multivariate analysis revealed that preoperative RF (OR, 10.2; 1.66-63.2; p = 0.006) and postoperative higher level of systemic vascular resistance index (SVRI) (OR, 1.19; 1.00-1.42; p = 0.020) were risk factors for RF in the chronic phase. On the other hand, among patients with preoperative low cardiac index (CI < 2.2 L/min/m2), preoperative RF was not risk factor for postoperative RF. Renal function improved immediately after CF-LVAD implantation, however, gradually decrease to the baseline after the transient improvement. Patients with preoperative RF significantly related to postoperative RF significantly, which was particularly noticeable in patients with preoperative CI was maintained. Elevated SVRI, which can be related to peripheral circulatory failure, was significant risk factor for postoperative RF and thus adequate management of elevated SVRI has the possibility to maintain postoperative renal function for CF-LVAD patients.

Outflow Graft Obstruction Causing Recurrent Heart Failure after Left Ventricular Assist Device Implantation

Outflow graft obstruction is a poorly described complication following continuous flow-left ventricular assist device (CF-LVAD) surgery. We sought to define the incidence of CF-LVAD outflow graft obstruction and assess clinical outcomes with a percutaneous treatment strategy. From January 2012 to June 2019, 252 CF-LVAD patients were managed at our institution. Patients with suspected LVAD outflow graft obstruction underwent comprehensive evaluation with Doppler echocardiography, cardiac computed tomography with angiography and invasive hemodynamic assessment followed by percutaneous intervention. Fourteen patients (5.6%) developed hemodynamically significant LVAD outflow graft obstruction at a rate of 0.03 events per patient-year. Outflow graft obstruction presented a mean of 34±18 months after surgery. Patients presented with heart failure (HF; 86%), low LVAD pump flow (93%), or both (79%). LVAD flow declined by an average of 2.1±0.8L/min (p<0.001). Outflow graft obstruction was caused by external graft compression (77%), stenosis of the aortic anastomosis (46%) and discrete kinking of the outflow cannula (46%); most patients presented with 2 or more lesions (69%). There were no cases of outflow graft thrombosis. External graft compression was uniformly due to build-up of fibrinous material between the outflow cannula and the protective external GoreTex graft. Outflow graft stenting was 100% successful and reduced the gradient from 80mmHg (IQR 58-100mmHg) to 13mmHg (IQR 10-20mmHg, Figure). There was no in-hospital mortality and few complications. Outflow graft stenting was durable; over a mean follow-up of 13±7 months, no patients had recurrent outflow graft obstruction. LVAD outflow graft obstruction is a relatively common and underappreciated cause of recurrent HF and LVAD dysfunction. Outflow graft stenting can be achieved with low morbidity and provides a long-term solution to this complication.

Non-Invasive TAPSE/PASP Ratio is Not Predictive of Early Right Ventricular Failure Post LVAD Implantation

Right ventricular failure (RVF) after LVAD implantation remains difficult to predict. RV-PA coupling assessed by echocardiographic assessment of the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) has shown to be prognostic in pulmonary hypertension and HFpEF. However, its utility in predicting RV failure after LVAD implantation has not been studied. We hypothesized that a low TAPSE/PASP ratio would be predictive of RV failure after LVAD. This was a single center retrospective observational study of patients who had first-time continuous flow LVAD implantation between 2012-2018. Pre-implant transthoracic echocardiograms were reviewed for each patient to obtain TAPSE and PASP. The primary outcome was early right ventricular failure defined as need for RVAD, inotrope duration >14 days, and/or pulmonary vasodilator use >48 hours. Differences between definition groups were assessed with two sample t-test. Results are reported as means with standard deviations. 254 patients were initially included in the LVAD cohort. Of those, 159 patients had complete echocardiogram data to calculate a TAPSE/PASP ratio. 40 patients (25%) had postoperative RV failure after LVAD implantation, of which 8 (25%) required RVAD. There was no difference in the TAPSE/PASP ratio in the RV failure cohort compared to the non-RV failure cohort (0.36 ± 0.14 versus 0.38 ± 0.18, respectively). However, there was a significant difference in pre-operative TAPSE/PASP ratio in patients who required RVAD compared to patients who did not require RVAD post-operatively (0.52 ± 0.17 versus 0.36 ± 0.14, respectively; p = 0.015). When restricting the definition of RV failure to need for RVAD or inotropes >14 days, there was no difference in the TASPE/PASP ratio between groups (p=0.77). In addition, a lower TAPSE/PASP ratio was associated with higher RA pressure (r= -0.27) and PVR (r= -0.28); however, there was no association between TAPSE/PASP and cardiac output. In a single center cohort of continuous flow LVAD patients, TAPSE/PASP as a surrogate for RV-PA coupling is not predictive of early RV failure post LVAD implantation. However, a higher ratio was associated with the need for RVAD. Further study is needed to determine if other metrics assessing RV/PA coupling are predictive of RV failure.

Ventricular arrhythmias following continuous‐flow left ventricular assist device implantation: A systematic review

Ventricular arrhythmias (VA) are not uncommon after continuous-flow left ventricular assist device (CF-LVAD) implantation. In this systematic review, we sought to identify the patterns of VA that occurred following CF-LVAD implantation and evaluate their outcomes. An electronic search was performed to identify all articles reporting the development of VA following CF-LVAD implantation. VA was defined as any episode of ventricular fibrillation (VF) or sustained (>30 seconds) ventricular tachycardia (VT). Eleven studies were pooled for the analysis that included 393 CF-LVAD patients with VA. The mean patient age was 57 years [95%CI: 54; 61] and 82% [95%CI: 73; 88] were male. Overall, 37% [95%CI: 19; 60] of patients experienced a new onset VA after CF-LVAD implantation, while 60% [95%CI: 51; 69] of patients had a prior history of VA. Overall, 88% of patients [95%CI: 78; 94] were supported on HeartMate II CF-LVAD, 6% [95%CI: 3; 14] on HeartWare HVAD, and 6% [95%CI: 2; 13] on other CF-LVADs. VA was symptomatic in 47% [95%CI: 28; 68] of patients and in 50% [95%CI: 37; 52], early VA (<30 days from CF-LVAD) was observed. The 30-day mortality rate was 7% [95%CI: 5; 11]. Mean follow-up was 22.9 months [95%CI: 4.8; 40.8], during which 27% [95%CI: 17; 39] of patients underwent heart transplantation. In conclusion, approximately a third of patients had new VA following CF-LVAD placement. VA in CF-LVAD patients is often symptomatic, necessitates treatment, and carries a worse prognosis.

Management and outcomes of left ventricular assist device-associated endocarditis: a systematic review.

Left ventricular assist device (LVAD)-associated endocarditis remains poorly studied, especially in newer continuous-flow LVADs (CF-LVADs). The aim of this review was to assess outcomes of patients with LVAD-associated endocarditis, as stratified by CF-LVAD and pulsatile LVAD (P-LVAD) use as well as by different interventions and pathogen types. An electronic search was performed to identify studies in the English literature on LVAD-associated endocarditis. Overall, 16 articles with 26 patients were included; seven had CF-LVADs and 19 had P-LVADs; time to development of endocarditis was 91 days (152 vs. 65 days, respectively, P=0.05). Eleven of 25 patients were treated with antibiotics only. Remaining 14 patients received antibiotics, however, they also underwent additional surgical intervention. One patient was treated with embolization alone for mycotic aneurysm and was therefore excluded. At a median follow-up time of 344 days post implant, there was no difference in overall mortality between CF-LVAD and P-LVAD-associated endocarditis patients (57.9% vs. 42.9%, P=0.81). Patients who underwent additional surgical intervention had higher overall survival compared to those treated with antibiotics alone (71.4% vs. 27.3%, P=0.07); with no difference in outcomes amongst those who underwent surgical device exchange as compared to heart transplantation (80.0% vs. 66.7%; P=0.23). Compared to patients with P-LVADs, CF-LVAD patients appeared to be resistant to early development of LVAD-associated endocarditis. There was a trend towards high survival observed amongst patients who underwent additional surgical intervention as compared to those treated with antibiotics alone, with no difference amongst surgical device exchange as compared to heart transplantation. Advantages of additional surgical intervention vs. medical therapy alone deserves further exploration to determine its applicability in CF-LVADs.

P1671Subclinical persistent hemolysis may affect late renal function deterioration after HeartMateII implantation

Abstract Background Late renal function dysfunction is an increasingly recognized complication in continuous flow left ventricular assist device (CF-LVAD) patients. Although hemolysis is prevalent in CF-LVAD patients and hemolysis may deteriorate renal function, the influence of persistent hemolysis on renal function in CF-LVAD patients remains to be investigated. Purpose To investigate the influence of persistent hemolysis on renal function in CF-LVAD patients, using lactate dehydrogenase (LDH) as a sensitive marker of hemolysis. Methods Excluding patients who died or underwent pump exchange for pump thrombosis, we retrospectively reviewed 65 consecutive adults who underwent HeartMateII implantation in our center from May 2011 to October 2017. Patient characteristics, chronotropic change of estimated glomerular filtration rate (eGFR) and LDH values weekly for 4 weeks and every 4 weeks between 4 and 48 weeks after implantation were collected. Then, calculating mean LDH during 48 weeks after implantation, study population was divided into low and high mean LDH groups at the median value of mean LDH. Results The median value of mean LDH was 304 U/l. Compared with low LDH patients, though high LDH patients were more likely female and had smaller body surface area, there were no significant difference in pre-operative eGFR between the groups (66.0±23.7 vs. 70.2±25.7 ml/min/1.73m2, p=0.495). After 40 weeks after implantation, high LDH patients had significantly lower eGFR than low LDH patients (71.0±23.7 vs. 87.1±31.4 ml/min/1.73m2, p=0.024). In multivariate linear regression analysis, mean LDH [parameter estimate: −0.10 (95% CI: −0.17 to −0.04), p=0.003] and post-operative pulse pressure [parameter estimate: 0.71 (95% CI: 0.05 to 1.37), p=0.036] were significantly associated with eGFR change during 48 weeks after HeartMateII implantation. Univariate and multivariate linear regression analysis for eGFR change Univariate parameter estimate 95% CI p value Multivariate parameter estimate 95% CI p value Bilirubin, mg/dl 9.97 3.82 to 16.13 0.002 6.55 −0.43 to 13.53 0.065 BNP, pg/ml 0.01 0.00 to 0.02 0.044 0.00 −0.01 to 0.01 0.528 Mean LDH during 4 to 48 weeks, U/l −0.11 −0.18 to −0.05 &lt;0.001 −0.10 −0.17 to −0.04 0.003 Pre-operative right atrial pressure, mmHg 1.43 0.35 to 2.51 0.010 −0.06 −1.52 to 1.40 0.935 Post-operative pulse pressure, mmHg 0.77 0.03 to 1.52 0.042 0.71 0.05 to 1.37 0.036 Conclusions High mean LDH and low pulse pressure were associated with a significant decrease in eGFR late after HeartMateII implantation. Subclinical persistent hemolysis may be associated with late renal function deterioration in CF-LVAD patients.