Left ventricular assist device-related infections and the risk of cerebrovascular accidents: a EUROMACS study.

OBJECTIVES: In patients supported by a durable left ventricular assist device (LVAD), infections are a frequently reported adverse event with increased morbidity and mortality. The purpose of this study was to investigate the possible association between infections and thromboembolic events, most notable cerebrovascular accidents (CVAs), in LVAD patients. METHODS: An analysis of the multicentre European Registry for Patients Assisted with Mechanical Circulatory Support was performed. Infections were categorized as VAD-specific infections, VAD-related infections and non-VAD-related infections. An extended Kaplan-Meier analysis for the risk of CVA with infection as a time-dependent covariate and a multivariable Cox proportional hazard model were performed. RESULTS: For this analysis, 3282 patients with an LVAD were included with the majority of patients being male (83.1%). During follow-up, 1262 patients suffered from infection, and 457 patients had a CVA. Cox regression analysis with first infection as time-dependent covariate revealed a hazard ratio (HR) for CVA of 1.90 [95% confidence interval (CI): 1.55-2.33; P < 0.001]. Multivariable analysis confirmed the association for infection and CVAs with an HR of 1.99 (95% CI: 1.62-2.45; P < 0.001). With infections subcategorized, VAD-specific HR was 1.56 (95% CI: 1.18-2.08; P 0.002) and VAD-related infections [HR: 1.99 (95% CI: 1.41-2.82; P < 0.001)] remained associated with CVAs, while non-VAD-related infections (P = 0.102) were not. CONCLUSIONS: Infection during LVAD support is associated with an increased risk of developing an ischaemic or haemorrhagic CVA, particularly in the setting of VAD-related or VAD-specific infections. This suggests the need of a stringent anticoagulation management and adequate antibiotic treatment during an infection in LVAD-supported patients.

Rate of thromboembolic and bleeding events in patients undergoing concomitant aortic valve surgery with left ventricular assist device implantation.

BACKGROUND: Significant aortic regurgitation at the time of left ventricular assist device (LVAD) implantation, requires concomitant aortic valve (AoV) replacement or repair. However, the impact of concomitant AoV surgery on morbidity remains unknown. Therefore, our aim is to determine the impact of concomitant AoV surgery on thromboembolic and bleeding events. METHODS: A retrospective IMACS registry study, including patients implanted from 2013 until September 2017. Differences between different concomitant AoV surgery modalities were analyzed. RESULTS: In total, 785 (5.1%) out of 15.267 patients (median age 58 IQR 49-66 years, 79% male) underwent concomitant AoV surgery (median age 63 IQR 54-69 years, 84% male); 386 (49%) patients received biological prostheses, 71 (9%) mechanical prostheses and 328 (42%) AoV repairs. In total, 54 (8%) patients with AoV surgery experienced a thromboembolic event and 1016 (9%) patients with no AoV surgery. Furthermore, concomitant AoV surgery was associated with an increased rate of all and nonsurgical bleedings. Following a multivariable Cox regression, concomitant AoV surgery remained an independent predictor for bleeding events. CONCLUSIONS: In LVAD patients undergoing concomitant AoV surgery, thromboembolic event rates were not higher, however both all and nonsurgical bleeding event rates were higher.

Survival and adverse events in patients with atrial fibrillation at left ventricular assist device implantation: an analysis of the European Registry for Patients with Mechanical Circulatory Support.

OBJECTIVES: Atrial fibrillation (AF) is a risk factor for mortality and cerebrovascular accidents (CVAs) and is common in patients with heart failure. This study evaluated survival and adverse events in patients with a left ventricular assist device (LVAD) and a history of AF in the European Registry for Patients with Mechanical Circulatory Support. METHODS: Patients with a continuous-flow LVAD, AF or sinus rhythm (SR) and a follow-up were included. Kaplan-Meier analyses for survival (including a propensity-scored matched analysis), freedom from CVA, pump thrombosis, bleeding and a composite of pump thrombosis/CVA were performed. To correct for covariate imbalance, a Kaplan-Meier (KM) analysis was performed after propensity score (PS) matching the groups. Finally, a Cox regression was performed for predictors of lower survival. RESULTS: Overall, 1821 patients (83% male) were included, with a median age of 57 years and a median follow-up of 13.1 months (interquartile range: 4.3-27.7). Preoperative Electrocardiogram (ECG) rhythm was AF in 421 (23.1%) and SR in 1400 (76.9%) patients. Patients with pre-LVAD AF had a lower ≤90-day (81.9% vs 87.1%, P = 0.0047) and 4-year (35.4% vs 44.2%, P = 0.0083) survival compared to SR. KM analysis with PS matching groups revealed a trend (P = 0.087) towards decreased survival. Univariable analyses confirmed pre-LVAD AF as a predictor for mortality, but the multivariable analysis did not. No difference in the rate of adverse events was found. An analysis of patients at 24 months revealed a higher rate of CVAs for pre-LVAD AF patients (77% vs 94.3%, P < 0.0001). CONCLUSIONS: Patients with pre-LVAD AF undergoing LVAD implantation had a worse survival. However, after performing a multivariate analysis, and PS matching analysis, AF was no longer significant, indicating a worser preoperative condition in these patients. Concerning thrombo-embolic events, only patients with pre-LVAD AF alive beyond 24 months have a higher risk of CVAs.

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): second EUROMACS Paediatric (Paedi-EUROMACS) report.

OBJECTIVES: A second paediatric report has been generated from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). The purpose of EUROMACS, which is operated by the European Association for Cardio-Thoracic Surgery, is to gather data related to durable mechanical circulatory support for scientific purposes and to publish reports with respect to the course of mechanical circulatory support therapy. Since the first report issued, efforts to increase compliance and participation have been extended. Additionally, the data provided the opportunity to analyse patients of younger age and lower weight. METHODS: Participating hospitals contributed pre-, peri- and long-term postoperative data on mechanical circulatory support implants to the registry. Data for all implants in paediatric patients (≤19 years of age) performed from 1 January 2000 to 1 July 2019 were analysed. This report includes updates of patient characteristics, implant frequency, outcome (including mortality rates, transplants and recovery rates) as well as adverse events including neurological dysfunction, device malfunction, major infection and bleeding. RESULTS: Twenty-nine hospitals contributed 398 registered implants in 353 patients (150 female, 203 male) to the registry. The most frequent aetiology of heart failure was any form of cardiomyopathy (61%), followed by congenital heart disease and myocarditis (16.4% and 16.1%, respectively). Competing outcomes analysis revealed that a total of 80% survived to transplant or recovery or are ongoing; at the 2-year follow-up examination, 20% died while on support. At 12 months, 46.7% received transplants, 8.7% were weaned from their device and 18.5% died. The 3-month adverse events rate was 1.69 per patient-year for device malfunction including pump exchange, 0.48 for major bleeding, 0.64 for major infection and 0.78 for neurological events. CONCLUSIONS: The overall survival rate was 81.5% at 12 months following ventricular assist device implant. The comparison of survival rates of the early and later eras shows no significant difference. A focus on specific subgroups showed that survival was less in patients of younger age (<1 year of age) (P = 0.01) and lower weight (<20 kg) (P = 0.015). Transplant rates at 6 months continue to be low (33.2%) The fact that the EUROMACS registry is embedded within the European Association for Cardio-Thoracic Surgery Quality Improvement Programme offers opportunities to focus on improving outcomes.

Pediatric Ventricular Assist Device Support in the Netherlands.

BACKGROUND: This study aimed to evaluate the changes in heart transplantation (HTx) waiting list mortality following the introduction of the Berlin Heart EXCOR (BH EXCOR) in the Netherlands, as well as the occurrence of adverse events in these children. METHODS: A retrospective, single-center study was conducted including all pediatric patients (≤18 years) awaiting HTx. Patients were grouped in two eras based on availability of the BH EXCOR in our center, era I (1998-2006; not available) and era II (2007 to July 31, 2018; available). RESULTS: In total, 87 patients were included, 15 in era I and 72 in era II. Extracorporeal membrane oxygenator support was required in 1 (7%) patient in era I and in 13 (18%) patients in era II. Overall mortality (7/15 in era I vs 16/72 in era II; 47% vs 22%, P = .06) and transplantation rates (8/15 in era I vs 47/72 in era II; 53% vs 65%, P = .39) did not differ significantly. Eleven (39%) patients of the pediatric ventricular assist device (VAD) population died, with the predominant cause being cerebrovascular accidents (CVAs) in eight (29%) patients. Furthermore, 14 (50%) of the pediatric VAD patients survived to transplantation. Adverse events most frequently occurring in VAD patients included CVA in 14 (50%), mostly (68%) within 30 days after VAD implantation, and bleeding requiring rethoracotomy in 14 (50%), all within 30 days after VAD implantation. CONCLUSIONS: The introduction of the BH EXCOR has positively impacted the survival of pediatric patients with end-stage heart failure in our center. The predominant cause of death changed from end-stage heart failure in era I to CVA in era II. We emphasize the need for large prospective registry-based studies.

Outcomes of patients after successful left ventricular assist device explantation: a EUROMACS study.

AIMS: Sufficient myocardial recovery with the subsequent explantation of a left ventricular assist device (LVAD) occurs in approximately 1-2% of the cases. However, follow-up data about this condition are scarcely available in the literature. This study aimed to report the long-term outcomes and clinical management following LVAD explantation. METHODS AND RESULTS: An analysis of the European Registry for Patients with Mechanical Circulatory Support was performed to identify all adult patients with myocardial recovery and successful explantation. Pre-implant characteristics were retrieved and compared with the non-recovery patients. The follow-up data after explantation were collected via a questionnaire. A Kaplan-Meier analysis for freedom of the composite endpoint of death, heart transplantation, LVAD reimplantion, or heart failure (HF) relapse was conducted. A total of 45 (1.4%) cases with myocardial recovery resulting in successful LVAD explantation were identified. Compared with those who did not experience myocardial recovery, the explanted patients were younger (44 vs. 56 years, P < 0.001), had a shorter duration of cardiac disease (P < 0.001), and were less likely to have ischaemic cardiomyopathy (9% vs. 41.8%, P < 0.001). Follow-up after explantation could be acquired in 28 (62%) cases. The median age at LVAD implantation was 43 years (inter-quartile range: 29-52), and 23 (82%) were male. Baseline left ventricular ejection fraction was 18% (inter-quartile range: 10-20%), and 60.7% of the patients had Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 or 2. Aetiologies of HF were dilated cardiomyopathy in 36%, myocarditis in 32%, and ischaemic in 14% of the patients, and 18% had miscellaneous aetiologies. The devices implanted were HeartMate II in 14 (50%), HVAD in 11 (39%), HeartMate 3 in 2 (7%), and 1 unknown with a median duration of support of 410 days (range: 59-1286). The median follow-up after explantation was 26 months (range 0.3-73 months), and 82% of the patients were in New York Heart Association Class I or II. Beta-blockers were prescribed to 85%, angiotensin-converting enzyme inhibitors to 71%, and loop diuretics to 50% of the patients, respectively. Freedom from the composite endpoint was 100% after 30 days and 88% after 2 years. CONCLUSIONS: The survival after LVAD explantation is excellent without the need for heart transplantation or LVAD reimplantation. Only a minority of the patients suffer from a relapse of significant HF.

Course of Disease and Clinical Outcome of Infective Endocarditis in HIV-infected Individuals: A Systematic Review and Meta-analysis.

Infective endocarditis (IE) causes substantial morbidity and mortality if untreated. The clinical course of IE might be different in HIV-positive patients as a result of immune dysfunction. This systematic review investigates the clinical course of IE in HIV-positive compared to HIV-negative patients. A systematic search was performed in PubMed, EMBASE, and Cochrane Library and registered in PROSPERO (CRD42016048649). All articles from 1996 and onward addressing the clinical outcome of HIV-positive adults suffering from IE were reviewed and included based on predefined inclusion and exclusion criteria. A meta-analysis was performed for the outcome mortality. Twenty-three articles were included of which eight included HIVpositive patients only, and 15 compared HIV-positive to HIV-negative patients. Two studies included patients on antiretroviral therapy (ART). HIV and intravenous drug use (IVDU) were closely related. Mortality was higher in HIV-positive patients with a CD4 count below 200 cells/µl than in HIV-positive patients with a higher CD4 count, while mortality was similar for HIV-positive compared to HIV-negative patients (risk ratio = 0.86 [95% confidence interval: 0.53-1.40]). No difference was found in length of hospital stay or rehospitalization. Clinical outcomes were strongly related to the right- or left-sided endocarditis. The clinical course of IE is not different for patients with and without HIV. Clinical outcomes were mainly associated with other factors, such as IVDU and side of cardiac involvement, rather than HIV status.

Clinical outcomes of paediatric patients supported by the Berlin Heart EXCOR: a systematic review.

Ventricular assist devices (VADs) are widely accepted as therapy to bridge children to heart transplantation. We provide a systematic review of the current state of clinical outcomes in children after paediatric VAD support by the Berlin Heart EXCOR (BH EXCOR) device. A systematic literature search was performed in April 2018. Studies reporting clinical outcomes in at least 15 children supported by a BH EXCOR VAD were included. Additionally, we focused on outcomes in small children and compared outcomes of children supported by a left ventricular assist device (LVAD) versus children supported by a biventricular assist device (BiVAD). Eighteen publications fulfilled the inclusion criteria and were included in this systematic review. Mortality rates ranged from 6.3% [confidence interval (CI) 0.0-18.1%] to 38.9% (2.8-75.0%) while transplantation rates ranged from 37.0% (CI 18.8-55.2%) to 72.5% (CI 63.9-81.2%) and successful weaning rates from 0.0% to 20.7% (CI 6.0-35.5%). In children under 1 year of age, mortality rates ranged from 20.0% to 55.5% and transplantation rates ranged from 0.0% to 62.5%. BiVAD support seemed to result in worse clinical outcomes than LVAD support. Incidence of stroke ranged from 5.0% to 47.0% in all children supported with the BH EXCOR. Although a high incidence of adverse events such as stroke and pump thrombosis is reported, VAD support should be considered in children with end-stage heart failure awaiting heart transplantation. Further research is warranted, especially on optimal timing of device implantation and anticoagulation regimens.

Statistical primer: a cost-effectiveness analysis.

Cost-effectiveness analyses (CEAs) of new treatment strategies are increasingly reported. This can be a part of a clinical trial or as a separate study. Governments and healthcare payers frequently require a CEA to decide whether a new treatment strategy will be reimbursed. CEA is a framework to assess the effectiveness and costs of a new treatment strategy (e.g. a drug or intervention) when compared with a reference strategy. Effectiveness is often measured in life-years or quality-adjusted life-years, whereas costs consist of direct costs (the costs of the treatment), induced costs (downstream costs and cost offsets) and indirect costs. In this statistical primer, the rationale for assessing the economic consequences of new therapies is explained, followed by the fundamental concepts of CEAs, the different types of CEAs and an introduction to interpretation of CEAs. Finally, a real-world example of a CEA is discussed, comparing cost-effectiveness of transcatheter versus surgical aortic valve replacement in patients with severe aortic stenosis at intermediate surgical risk.