Bruno Schnegg

After a cardiac transplantation, the steering of immunosuppression requires an active search for acute cellular rejection (ACR). Surveillance with endomyocardial biopsy (EMB) is the gold standard. Given the costs and potential complications, there is growing interest in the use of non-invasive screening methods. Thus, we have conducted a systematic review and meta-analysis to evaluate the role of speckle-tracking echocardiography as a screening method for ACR. We searched PubMed (CENTRAL) and gray literature for studies presenting data on speckle tracking echocardiography in heart-transplant patients experiencing acute cellular rejection. The primary outcomes of the meta-analysis were left and right ventricular global longitudinal strain. We used random effects models for all our calculations. We pre-registered our meta-analysis with PROSPERO (CRD42024508654). By incorporating data from over 2000 biopsies included in 18 studies, we found that both left (LVGLS, MD -1.96, 95% CI -2.85 to -1.07, p < 0.0001), and right (RVGLS, MD -2.90, 95% CI -4.03 to -1.76, p < 0.00001) ventricular longitudinal strain were lower among patients without ACR. The change of LVGLS from baseline over time was also greater among patients experiencing ACR (MD -2.43, 95% CI -4.82 to -0.05, p = 0.045). Current data suggest that myocardial strain measured by speckle tracking echocardiography is affected in ACR and could potentially be used for early rejection detection as a rule-out strategy, leading to reduction of routine EMB in heart transplant follow-up.

Aims: Use of novel anticoagulation in mechanical circulatory support is controversial. We report the rationale and design of the ApixiVad pilot trial, a pilot study testing the safety of apixaban as an anticoagulant in patients bridged to transplant (BTT) or for destination (DT) with Heartmate 3 (HM3) left ventricular assist device (LVAD). Methods and results: Apixaban has been used in small non-randomized cohorts in LVAD patients and shown to be effective in ex vivo studies. The ApixiVAD study examines apixaban use in a multicentre, international, open-label, randomized, controlled trial aiming to include 50 BTT or DT HM3 patients with a 1:1 randomization ratio. This event-driven study has a maximum follow-up period of 24 months with interim analysis at 6 months. The primary outcome is death, thromboembolic events and major bleeding, including operative bleeding and immediate transplant outcomes. The secondary outcome focuses on patients’ quality of life related to anticoagulation. This investigator-driven pilot study is not powered to determine the non-inferiority of apixaban. An increase in primary outcome in the apixaban group of 20% will be considered a signal of harm. Conclusions: A positive outcome in the ApixiVAD study would provide the basis for future, larger, pivotal anticoagulation trials in LVAD patients.

BackgroundThe number of patients treated by ventricular assist devices (VAD) and the duration of VAD treatment is increasing. One of the main complications in terms of morbidity and mortality for VAD patients are microbial infections. With this study, we aimed to investigate the epidemiology and microbiological characteristics of infections occurring in a VAD population to identify modifiable factors. MethodsWe retrospectively analyzed patient characteristics, treatments and outcomes of VAD-specific/related infections. All patients implanted in our institution with a continuous flow VAD between January 2009 and January 2019 were included. Risk factors for VAD infection were assessed using simple and multiple linear regressions. ResultsOf the 104 patients screened, 99 were included in the analysis, the majority of which were men (78%). At implantation, the mean age was 56 years and the median time on VAD support was 541 days. The overall infection rate per year per patient was 1.4. Forty-seven patients (60%) suffered from VAD-specific/related infection. Half of all infection episodes occurred in the first 4 months but the proportion of VAD-specific/related infection was higher after the first 4 months (74% of all infection). Using regression models, no patient specific risk factors were associated with VAD-specific/related infections. ConclusionNo predictive factors for infection during VAD support were identified in this study. By extension, diabetes, renal insufficiency, age or high BMI are not sufficient to deny a patient access to ventricular support.

Background: Implanted cardioverter defibrillators (ICDs) and left ventricular assist devices (LVADs) are established interventions that prolong life in advanced heart failure, but their combination has not been demonstrated as beneficial. Electromagnetic interference (EMI) produced by a LVAD can preclude ICD interrogation with external programmers. We undertook a systematic evaluation of the LVAD–ICD interaction “in‐vitro” to clarify the extent of this interaction.Methods: Using explanted ICDs and VADs in a mock physiological rig, we assessed interrogation and reprogramming of ICD devices in the presence of a running LVAD. When connectivity between the ICD programmer and the ICD failed, we attempted three different techniques to re‐establish connectivity: (1) Electromagnetic shielding of the ICD with a pseudo‐faraday cage; (2) altering the LVAD speed; and (3) increasing the distance between the VAD and the ICD.Results: We tested a total of 24 ICDs from different manufacturers in the presence of the Heartware (HW) and HeartMate 3 (HM3) LVADs. With HW, we only observed interaction with Biotronik ICD devices at very close range (0–6 cm). With HM3, only Medtronic ICD devices showed no interaction. Interactions could be mitigated by increasing the VAD–ICD distance.Conclusions: LVADs, notably the HM3, produce EMI that interferes with the communication between an ICD and its respective programmer. This may need to be considered when choosing the type of VAD to implant in patients with a previously implanted left‐sided ICD. The only safe way to regain connectivity is to increase the distance between the VAD and the ICD, with patients raising their arm above their head.

The use of continuous flow ventricular assist devices (cf‐VAD) necessitates systemic anticoagulation, routinely with vitamin K antagonism (VKA). Newer direct oral anticoagulants (DOACs) have significant advantages over VKA providing a predictable level of systemic anticoagulation without frequent monitoring or strict dietary surveillance. Despite randomised evidence to demonstrating their usefulness in several conditions including atrial fibrillation, there is limited data pertaining to their use in cf‐VAD patients. Early reports of adverse outcomes has resulted in a Class III recommendation, advising against DOACs generally in cf‐VAD patients¹. Recent reports suggest there may be a role for certain DOACs; as such we present a systematic review identifying studies reporting DOAC uses in patients with a cf‐VAD. We identified eight pertinent studies, including a single randomised controlled trial and seven case reports/series. Limited numbers and significant study heterogeneity limits interpretation, however Factor Xa inhibitors appear to be feasible alternatives, favourable to direct thrombin inhibitors, although further research is required.