Aspirin resistance in patients with ventricular assist devices-A follow-up study.

BACKGROUND: Despite combined anticoagulation therapy consisting of a vitamin K antagonist and an antiplatelet agent, thromboembolic complications often occur in patients with a left ventricular assist device (LVAD). In addition, bleeding events are also common. Resistance to antiplatelet drugs is a well-known phenomenon; however, the utilization of laboratory chemistry testing for the presence of such resistance, and then switching therapy, is controversial. METHODS: We tested 132 patients with LVAD (HeartWare n = 57, HeartMate II n = 22, HeartMate 3 n = 53) on acetylsalicylic acid (ASA) therapy for resistance and followed them for a maximum of 7 years regarding pump thrombosis. Light transmission aggregometry (LTA) and impedance aggregometry (IPA) were performed for testing platelet function. RESULTS: We could show that patients with ASA resistance displayed an increased risk of pump thrombosis, regardless of the test used (LTA: OR = 6.20, CI [1.86-20.64], p = 0.003; IPA: OR = 12.14, CI [3.00-49.07], p < 0.001). In patients with a HeartMate 3, we could not detect any pump thrombosis associated with aspirin resistance. Furthermore, there was no significant difference in bleeding events between patients with ASA resistance and ASA responders. CONCLUSION: Laboratory testing of ASA resistance seems to be a good tool to detect an increased risk of pump thrombosis, at least for patients with a HeartWare or HeartMate II. The extent to which these thromboses can be prevented with a change of medication has to be investigated in further studies. No pump thrombosis was detected in patients with a HeartMate 3, and the question should be asked as to what constellation of underlying and concomitant diseases must be present to justify ASA therapy for these patients.

Professional Employment in Patients on Ventricular Assist Device Support-A National Multicenter Survey Study.

This study aimed to assess patients of working age returning to professional employment as a surrogate marker for functional recovery and psychosocial reintegration after ventricular assist device (VAD) implantation. A national, multicenter study considered professional employment and its relationship to sociodemographic, psychosocial, and clinical adverse outcomes in outpatients on VAD support. Patient-reported outcome measures were administered. The survey had a 72.7% response rate. Mean age of 375 subjects was 58 ± 11 years, 53 (14%) were female. Thirty-five patients (15.15%; 95% confidence interval [CI] = 10.9-20.6) were employed, and the majority of them (n = 29, 82.9%) were bridged to transplantation. A regression model after variable selection revealed younger age (odds ratio [OR] = 0.95; 95% CI = 0.91-0.98; p < 0.005), and higher education (OR = 3.05; 95% CI = 1.72-5.41; p < 0.001) associated with professional employment. Employed patients reported higher health-related quality of life (HRQoL) (Kansas City Cardiomyopathy Questionnaire [KCCQ] overall sum-score, OR = 1.04; 95% CI = 0.92-1.07; p < 0.007), the OR for those employed was 2.18 (95% CI = 0.89-5.41; p < 0.08) indicating no significant relation for employment and a history of adverse events. In this sample, professional employment was rather small; the likelihood of adverse events was not significantly different between groups. Those employed perceived better overall HRQoL, which may encourage clinicians to support professional employment for selected patients on VAD support.

Driveline infection according to driveline positioning in left ventricular assist device implant recipients.

We conducted a prospective, open-labeled, clinical trial, with a two-by-two factorial design, of argon cold plasma application and two different types of driveline positioning for the prevention of driveline infection (DLI) in 80 patients with a left ventricular assist device (LVAD) implant. Here, we present the results of intracorporeal loop positioning (n = 40) versus no intracorporeal loop positioning (n = 40). Patients were followed up for 1 year. According to the Driveline Expert STagINg and carE grading (DESTINE) system, a DLI was considered in case of a stage 2 or higher graded infection. During follow-up, 29 (36%) patients experienced a DLI, 16 in the group with intracorporeal loop positioning and 13 in the group with no intracorporeal loop positioning. Kaplan-Meier estimates of freedom from DLI showed no statistically significant difference between study groups during follow-up (p = 0.33). In detail, 30-day freedom from DLI was for the groups with and without intracorporeal loop positioning 92 and 92%, respectively, and 1-year freedom from DLI was 51 and 62%, respectively. In conclusion, this controlled clinical trial was unable to show a statistically significant difference in freedom from DLI during one year of follow-up in groups with or without intracorporeal loop positioning. However, larger trials have to confirm these results.

High level of psychosocial adjustment in patients on ongoing ventricular assist device support in the years one to three after VAD implantation-A national multi-center Study.

BACKGROUND: Advanced heart failure therapies such as durable ventricular assist device (VAD) support require psychosocial adjustment for those affected. Since VAD implantation has become an established treatment strategy, a focus on psychosocial factors is needed. OBJECTIVES: To investigate the construct of psychosocial adjustment and to further understand the role of social support. METHODS: In a nation-wide, multi-center, cross-sectional study, we recruited 393 participants with ongoing VAD support (3mts-3yrs on device; clinicaltrials.gov ID: NCT04234230). Patient demographics, psychosocial adjustment (perceived social support, anxiety, depression, and quality of life), and major adverse events (thromboembolic events, bleeding, driveline infections) were assessed. RESULTS: Overall, 85.8 % of the sample were male; mean age was 58.3 years (range 18-85). The majority of the sample (89.3 %) reported normal to high perceived social support. Participants expressed symptoms of anxiety within the normal range (M=6.0±3.9), mildly elevated depressive symptoms (HADS: M=7.6±2.9; PHQ-9: M=6.2±4.7), and good quality of life (KCCQ: M=65.3±17.9). Higher perceived social support was associated with lower levels of anxiety and depression, and higher levels of quality of life within our sample (all p<0.001). Driveline infection was the most prevalent adverse event (0.304 infections per person-years [32.6 % of patients]). Binary logistic regression models did not identify significant associations for the occurrence of adverse events and variables of psychosocial adjustment. CONCLUSION: Our sample perceived high levels of psychosocial adjustment. High perceived social support was associated with better outcomes in levels of anxiety, depression, and quality of life, demonstrating potential for the future development and evaluation of targeted multi-professional social support interventions including peer- and caregiver support.

Argon Cold Plasma Use and Driveline Infection in Left Ventricular Assist Device Implant Recipients.

We conducted a prospective open-labeled, clinical trial, with a two-by-two factorial design, of argon cold plasma (ACP) application and two different types of driveline positioning for the prevention of driveline infection (DLI) in patients with a left ventricular assist device (LVAD) implant. Here, we present the results of ACP application versus no ACP application. Eighty patients were allocated to the control group (no preventive ACP use; n = 40) or ACP group (preventive ACP use for 30 days post-LVAD implantation; n = 40). Patients were followed up for 1 year. The secondary endpoint was survival on device. Preventive ACP use improved 30 day freedom from DLI significantly (100% vs. 85%; p = 0.012); results remained significant at 6 months (92% vs. 69%, p = 0.007) and were 55% and 60%, respectively ( p = 0.65) at 1 year follow-up. With respect to survival on device, results in the control and ACP groups did not differ significantly at 30 days (97.5% vs. 100%, respectively; p = 0.32), but tended to be lower in the control group than in the ACP group at 1 year follow-up (74% vs. 90%, respectively; p = 0.09). In conclusion, preventive ACP use was able to significantly reduce DLI both during the application period and up to 6 months after LVAD implantation.

Long-term assist device patients admitted to ICU: Tips and pitfalls.

Left ventricular assist device (LVAD) therapy is well-established in the treatment of end-stage cardiac failure. Indications are bridge to transplant (BTT), bridge to candidacy (BTC), bridge to recovery (BTR), and destination therapy (DT). The durability and adverse event (AE) rate of LVADs have improved over the years. However, due to donor shortage, the duration of support in the BTT population has increased tremendously; similarly, DT patients are on the device for a long time. Consequently, the number of readmissions of long-term LVAD patients has increased. In cases of severe AEs, intensive care unit (ICU) treatment can be necessary. Infectious complications are the most common AE. Furthermore, embolic or hemorrhagic strokes can occur due to foreign surfaces, acquired von Willebrand syndrome, and anticoagulation treatment. Another consequence of the coagulative status, in combination with the continuous flow, are gastrointestinal bleeding events. Moreover, in most patients, an isolated LVAD is implanted, and this involves the risk of late right heart failure. Adjustment of pump speed and optimization of the volume status can help solve this issue. Malignant arrhythmias, pre-existing or de novo after LVAD implantation, can be a life-threatening AE. Antiarrhythmic medical therapy or ablation are potential treatment options. As for specific LVADs, the Medtronic HeartWare™ ventricular assist device (HVAD) is not manufactured and distributed currently; however, 4000 patients are still on the device. Pump thrombosis can occur, wherein thrombolytic therapy is the first-line treatment option. Additionally, the HVAD can fail to restart after controller exchange due to technical issues, and precautions must be taken. The Momentum 3 trial showed superior survival without pump exchange or disabling stroke in patients treated with the HeartMate 3Ⓡ (HM3; Abbott, Abbott Park, IL, USA) device in comparison to the HeartMate II (HMII). However, in a few cases, a twisted graft or bio debris formation between the outflow graft and bend relief could be observed, causing outflow graft obstruction. Patients on LVADs are still heart failure patients, in many cases with comorbidities. Therefore, many situations can occur requiring ICU treatment. Ethical aspects should always be the focus when taking care of these patients.

Cardiac Muscle Training-A New Way of Recognizing and Supporting Recovery for LVAD Patients in the Pediatric Population.

Patients with refractory heart failure due to chronic progressive cardiac myopathy (CM) may require mechanical circulatory support as a bridge to transplantation. A few patients can be weaned from support devices if recovery can be achieved. The identification of these patients is of great importance as recovery may be missed if the heart is unloaded by the ventricular assist device (VAD). Testing the load-bearing capacity of the supported left ventricle (LV) by temporarily and gradually reducing mechanical support during cardiac exercise can help identify responders and potentially aid the recovery process. An exercise training protocol was used in 3 patients (8 months, 18 months and 8 years old) with histological CM findings and myocarditis. They were monitored regularly using clinical information and functional imaging with VAD support. Echocardiographic examination included both conventional real-time 3D echocardiography (RT3DE) and speckle tracking (ST). A daily temporary reduction in pump rate (phase A) was followed by a permanent reduction in rate (phase B). Finally, pump stops of up to 30 min were performed once a week (phase C). The final decision on explantation was based on at least three pump stops. Two patients were weaned and successfully removed from the VAD. One of them was diagnosed with acute viral myocarditis. The other had chronic myocarditis with dilated myopathy and mild interstitial fibrosis. The noninvasive assessment of cardiac output and strain under different loading conditions during VAD therapy is feasible and helps identify candidates for weaning despite severe histological findings. The presented protocol, which incorporates new echocardiographic techniques for determining volume and deformation, can be of great help in positively guiding the process of individual recovery, which may be essential for selecting and increasing the number of patients to be weaned from VAD.

Evolution of thrombolytic therapy in patients with HeartWare ventricular assist device thrombosis: a single-institutional experience.

OBJECTIVES: Pump thrombosis remains a major challenge in heart failure patients with left ventricular HeartWare assist device. Current International Society for Heart and Lung Transplantation recommendations favour surgical pump exchange over lysis because safety and efficacy of lysis has been controversially reported. This study summarizes our experience on our HeartWare thrombosis prevention strategy as well as thrombolysis through implementation of our institutional standardized HeartWare assist device protocol. METHODS: Outcomes of all HeartWare thrombosis patients admitted between 2010 and 2020 were analysed. Thrombolysis therapy using tissue plasminogen activator was used as the first-line therapy in this study and thrombolysis therapy efficacy was defined as freedom from stroke, bleeding, recurrent HeartWare assist device thrombosis or surgical device exchange within 30 days after lysis application. RESULTS: A total of 507 patients have been included in this study and 66 patients (13%) collectively developed a first HeartWare-thrombosis after a median of 12 months (8-22 months) after HeartWare implantation. Forty patients were treated with unstandardized lysis, of whom 7 patients had thrombolysis associated complications, such as incomplete thrombus resolution requiring surgical pump exchange in 4 patients, but also intracranial haemorrhage occurring in 3 patients. Three patients died in the non-protocol group. Eight device thrombosis patients were treated according to our protocol, showing no lysis-associated complication. CONCLUSIONS: Despite current recommendations, preferring surgical HeartWare pump exchange in thrombosis, thrombolysis therapy for first HeartWare thrombosis can be safe and effective in a standardized protocol setting, including anticoagulation adjustment and intensified blood pressure control management.

Clinical findings associated with incomplete hemodynamic left ventricular unloading in patients with a left ventricular assist device.

INTRODUCTION AND OBJECTIVES: The effect of a centrifugal continuous-flow left ventricular assist device (cfLVAD) on hemodynamic left ventricular unloading (HLVU) and the clinical conditions that interfere with hemodynamic optimization are not well defined. METHODS: We retrospectively evaluated the likelihood of incomplete HLVU, defined as high pulmonary capillary wedge pressure (hPCWP)> 15mmHg in 104 ambulatory cfLVAD patients when the current standard recommendations for cfLVAD rotor speed setting were applied. We also evaluated the ability of clinical, hemodynamic and echocardiographic variables to predict hPCWP in ambulatory cfLVAD patients. RESULTS: Twenty-eight percent of the patients showed hPCWP. The variables associated with a higher risk of hPCWP were age, central venous pressure, absence of treatment with renin-angiotensin-aldosterone system inhibitors, and brain natriuretic peptide levels. Patients with optimal HLVU had a 15.2±14.7% decrease in postoperative indexed left ventricular end-diastolic diameter compared with 8.9±11.8% in the group with hPCWP (P=.041). Independent predictors of hPCWP included brain natriuretic peptide and age. Brain natriuretic peptide <300 pg/mL predicted freedom from hPCWP with a negative predictive value of 86% (P <.0001). CONCLUSIONS: An optimal HLVU can be achieved in up to 72% of the ambulatory cfLVAD patients when the current standard recommendations for rotor speed setting are applied. Age, central venous pressure and therapy with renin-angiotensin-aldosteron system inhibitors had a substantial effect on achieving this goal. Brain natriuretic peptide levels and the magnitude of reverse left ventricular remodeling seem to be useful noninvasive tools to evaluate HLVU in patients with functioning cfLVAD.

Self-management for patients on ventricular assist device support: a national, multicentre study: protocol for a 3-phase study.

INTRODUCTION: Self-management (SM) may facilitate patient participation and involvement to become active and knowledgeable partners in the care of complex chronic conditions such as ventricular assist device (VAD) therapy. The 'SM model for patients on VAD support' will serve to distinguish between SM components, and will guide the development, implementation and evaluation of an evidence-based curriculum. METHODS AND ANALYSIS: This is a 3-phase, multicentre study. In phase 1, a prevalence study will be performed. Phase 2 aims to develop an evidence-based, interprofessional curriculum for SM support for VAD patients. In phase 3, a non-blinded block-randomised controlled trial (RCT), allocation ratio 1:1, intervention group superiority, with an unblinded multifacetted intervention with assessments before (T1) and after (T2) the intervention, and two follow-up assessments at three (T3), and 12 (T4) months after VAD implantation, will be performed. The curriculum guides the intervention in the RCT. Patient recruitment will consider centre-related volume: power analyses require 384 patients for phase 1, and 142 patients for phase 3. ETHICS AND DISSEMINATION: Ethical considerations will be continuously taken into account and approved by the institutional review boards. Central ethical review board approval has been obtained by the Albert-Ludwigs University Freiburg. This study will be performed in concordance with the Declaration of Helsinki and the European data protection law. Publications will exclusively report aggregated data and will be distributed in the scientific community, and patient support groups. Report languages will be German and English. TRIAL REGISTRATION NUMBERS: NCT04234230 and NCT04526964; Pre-results.

Clinical implications of late-onset right ventricular failure after implantation of a continuous-flow left ventricular assist device as bridge to transplantation.

OBJECTIVES: The development of late-onset right ventricular failure (LoRVF) that occurs months after a continuous-flow left ventricular assist device (LVAD) is implanted is a clinical problem that warrants investigation. Our goal was to study the incidence, clinical manifestations and prognosis of LoRVF in a population of patients who received an LVAD as bridge to transplantation. METHODS: Data were analysed from 97 consecutive patients who received an LVAD as bridge to transplantation and underwent a right heart catheterization at least 3 months after receiving an LVAD implantation. LoRVF was defined if both haemodynamic criteria of a central venous pressure >16 mmHg and a cardiac index <2.3 l/min/m2 were present. Clinical and echocardiographic variables, hospitalizations for heart failure and survival were compared between patients with and without LoRVF. RESULTS: LoRVF was diagnosed in 13% of patients after a median time of 11 months. Patients with LoRVF presented preoperative worse right ventricular (RV) dilatation and severe tricuspid regurgitation. LORVF was also associated with postoperative RV dilatation, moderate to severe tricuspid regurgitation and lower tricuspid annular plane systolic excursion. LoRVF resulted in increased brain natriuretic peptide levels and the need for diuretics, lower haemoglobin levels and a higher rate of atrial fibrillation and gastrointestinal bleeding. The rate of hospitalizations for heart failure in patients with LoRVF was 46%, and 15% required an urgent transplantation due to refractory RV failure. LoRVF decreased global survival and survival free from hospitalizations for heart failure (P < 0.0001). CONCLUSIONS: LoRVF after the implantation of an LVAD as bridge to transplantation is associated with higher morbidity and lower survival. The results suggest that the routine use of a right heart catheterization and transthoracic echocardiography may contribute to an early diagnosis before further severe complications due to refractory RV failure might occur. ID NUMBER OF THE IRB APPROVAL: AZ-2019-521 on 10 July 2019.

Risk factors of early right ventricular failure in patients undergoing LVAD implantation with intermediate Intermacs profile for advanced heart failure.

BACKGROUND: The clinical profile of left ventricular assist device (LVAD) candidates is rapidly changing, with increasing proportion of patients in more stable clinical conditions. However, early postoperative right ventricular failure (eRVF) is still one of the cornerstones associated with increased mortality and the preoperative recognition of associated risk factors remains challenging. The aim of this study was to identify predictive parameters for eRVF after LVAD implantation in patients with preoperative intermediate Intermacs (InM) risk profile 3-5. METHODS: Preoperative laboratory, echocardiography, and right heart catheterization data collected from 80 patients with InM profile 3-5 before LVAD implantation were retrospectively tested with respect to their ability to predict the risk for eRVF after the implantation of a continuous-flow LVAD. RESULTS: Preoperative higher bilirubin and blood urea nitrogen (BUN) levels, higher Model for End-stage Liver Disease score, lower estimated glomerular filtration rate, and higher central venous pressure to pulmonary capillary wedge pressure ratio (CVP/PCWP) were associated to higher risk of eRVF. Regarding the echocardiographic assessment, higher end diastolic linear dimensions of the RV, higher basal end diastolic RV linear dimension to LV ratio, severe tricuspid regurgitation, lower tricuspid annular plane systolic excursion, and lower RV fractional area contraction identified patients with higher risk for eRVF. In the multivariable analysis, a CVP/CPWP > 0.55 (odds ratio [OR]: 4, 95% confidence interval [CII]: 1.4-11.8;P = .01) and BUN > 44.5 mg/dL (OR: 6.6, 95% CI: 1.51-23; P = .011) independently predicted the risk of eRVF. CONCLUSION: Preoperative BUN > 44.5 mg/dL and CVP/PCWP > 0.55 are associated to an increased risk of eRVF following LVAD implantation in intermediate InM patients.

Prevention and early treatment of driveline infections in ventricular assist device patients - The DESTINE staging proposal and the first standard of care protocol.

Mechanical circulatory support (MCS) using left ventricular assist devices (LVAD) have considerably improved the quality of life and survival rate of patients with end-stage heart failure. Despite substantial technological progress, major challenges with regard to VAD-specific and VAD-related infections have hitherto hindered the broader application of this promising therapy approach. Driveline infections (DLI) range among the main adverse events experienced in LVAD patients. However, many centers still apply their own protocol for driveline exit site (DLES) care and an international standard on prevention, reduction and early treatment of DLI after the perioperative period has not yet been defined. In March 2019, VAD coordinators and cardiac surgeons from Germany and Austria met to develop a standard of care procedure (SOP) as well as a new staging approach with recommended actions for treatment of VAD carriers. In this Driveline Expert STagINg and carE (DESTINE) study group we developed a 10-step SOP for DLES care with emphasis on essentials such as clean and save preparation, sterile dressing change and secure driveline immobilization. An advanced wound staging approach was defined with recommended actions for prevention, early detection and stage-related management of DLI. Broad consensus was reached on the fact that an interdisciplinary approach both in DLES care and DLES healing disorder awareness is required to prolong infect-free survival times on MCS as well as to ensure high patient compliance and quality of life. In conclusion, a new detailed SOP for appropriate DLES care and an advanced wound staging approach for prevention and management of DLI were defined on an expert level applicable for VAD clinicians, practitioners and care givers in Central Europe.

Long-Term Mechanical Circulatory Support in Pediatric Patients.

This retrospective study reviews our results regarding the long-term support in pediatric patients using two ventricular assist systems between January 2008 and April 2014. We implanted the Berlin Heart EXCOR in 29 patients (median age 3.4 years [interquartile range (IQR) 0.2-16.5], median weight 13 kg [IQR 4.2-67.2]). Twenty-two patients (75.8%) received a left ventricular assist device. Three patients (10.3%) had single-ventricle physiology. One patient (3.4%) had mechanical mitral valve prosthesis. The HeartWare System was implanted in nine patients. The median age was 15.6 years (IQR 12.2-17.9), and the median weight was 54.9 kg (IQR 27.7-66). In the Berlin Heart group, the median support time was 65 days (IQR 4-619), with 3647 days of cardiac support. Nineteen patients (65.5%) were transplanted, six patients (20.7%) recovered, one patient (3.4%) is on support, and three patients (10.3%) died on support. Survival rate was 89.7%. Fourteen blood pumps had been exchanged. Four patients (13.8%) had local signs of infection, and three patients (10.3%) had neurological complications. In the HeartWare group, the median support time was 180 days (IQR 1-1124), with 2839 days of cardiac support. Four patients (44.4%) had local signs of infection, and three (33.3%) had neurological complications. Eight patients (88.9%) have been transplanted, and one patient (11.1%) died on support. Survival rate was 88.9%. Excellent survival is possible after long-term mechanical circulatory support in patients with two- and single-ventricle physiology with a low rate of adverse events.

Comparison of biventricular and left ventricular assist devices for the management of severe right ventricular dysfunction in patients with end-stage heart failure.

Right ventricular failure (RVF) exposes ventricular assist device (VAD) recipients to a high risk of death, but its management has not yet been standardized. We report three separate management strategies used for VAD recipients that present with RVF at a single center: 1) Thoratec paracorporeal biventricular VAD implantation, 2) left ventricular assist device (LVAD) implantation with temporary CentriMag right ventricular assist device (RVAD), and 3) LVAD combined with inotropic therapy. We retrospectively compared the preoperative data, the clinical outcomes, and the rates of adverse events in 84 biventricular assist device (BiVAD) recipients and 89 LVAD recipients presenting with postoperative RVF (57 were treated with a temporary RVAD and 32 were managed medically). Risk factors for death were analyzed. The BiVAD recipients were significantly younger, more critically ill at the time of device implantation, and required extracorporeal membrane oxygenation, an intraaortic balloon pump, mechanical ventilation, inotropes, or cardiopulmonary resuscitation significantly more often (at the time of device implant) than the LVAD recipients with RVF. The 6 month mortality was comparable in the two groups: 44 BiVAD patients (52%) and 38 LVAD patients (43%). Age, previous cardiac surgery, low platelet count, increased creatinine levels, the use of preoperative mechanical ventilation, and the need for a temporary RVAD were associated with 6 month mortality. The occurrence of RVF at the time of device implantation is a severe situation; it is associated with excess mortality, even if it is managed using a BiVAD or a LVAD with a temporary RVAD, probably because of the high preoperative risk profiles of the patients. In all cases, RVF must be managed quickly.