Pre-Implant Immune Status is Associated with Infection Risk After Left Ventricular Assist Device Implantation.

Purpose: Infection is the most common complication after left ventricular assist device (LVAD) implantation. The immune status of LVAD patients is relevant for the incidence and severity of infection, but it is unknown if there is a predisposing immune status prior to LVAD implantation that contributes to an increased risk for infection in the post-implant period. We analyzed the pre-LVAD immune status in patients with infection within 3 months after LVAD implantation in comparison to infection-free patients. Patients and Methods: Fifty-four consecutive LVAD patients were included in this study. According to their infectious history in the first 3 months after LVAD implantation, these patients were grouped into an infection (n=23) and an infection-free group (n=31). Pre-LVAD blood samples were obtained for flow cytometric analysis of immunological parameters including B cells, subsets of T, dendritic and natural killer cells. Patient-specific, clinical and laboratory data were recorded. Results: Blood count analysis prior to LVAD implantation showed comparable counts of erythrocytes (p=0.19), platelets (p=0.33) and leukocytes (p=0.50) between patients with infection and infection-free patients in the post-implant period. Patients with infection in the first 3 months after LVAD implantation had lower concentrations of lymphocytes (p=0.02). Forty percent of the patients with infection showed more often pre-LVAD neutrophil-to-lymphocyte ratios (NLR) >7 than patients without infection in the first 3 months after LVAD implantation (14%, p=0.05). Patients with infection already had lower percentages of CD3+ T cells (p=0.03), CD19+ B cells (p<0.01), BDCA2+ pDCs (p=0.03) and BDCA4+ plasmacytoid DCs (pDCs) (p=0.05) prior to LVAD implantation than infection-free patients. Conclusion: Our results demonstrated that patients with infection in the early post-implant period showed lower concentrations of lymphocytes, especially of CD3+ T cells and CD19+ B cells, decreased percentages of BDCA2+ and BDCA4+ pDCs, and had more often NLRs >7 indicating moderate-to-severe inflammation. Thus, we identified specific immunological changes pre-LVAD that could help to identify patients at risk for infection in the early post-implant period.

Body mass index-dependent immunological profile changes after left ventricular assist device implantation.

Purpose: Infection is a common complication following left ventricular assist device (LVAD) implantation. Patients with obesity are particularly at risk due to their high percentage of adipose tissue and the resulting chronic inflammatory state and resulting immunological changes. This study investigated changes of immunological parameters in relation to body mass index (BMI) during the first year after LVAD implantation. Methods: Blood samples were obtained prior to LVAD implantation and at 3 (1st FU), 6 (2nd FU) and 12 mo (3rd FU) after LVAD implantation. Patients were divided into three groups (normal weight: BMI of 18.5-24.9 kg/m2; n=12; pre-obesity: 25.0-29.9 kg/m2; n=15; obesity: ≥ 30.0 kg/m2; n=17) based on their BMI at the time of LVAD implantation. Flow cytometric analyses for CD4+ and CD8+ T cells, regulatory T cells (Tregs), B cells as well as dendritic cells (DCs) were performed. Results: After LVAD implantation, obese patients (0.51 ± 0.20%) showed a higher proportion of overall DCs than normal-weight (0.28 ± 0.10%) and pre-obese patients (0.32 ± 0.11%, p<0.01) at 3rd FU. The proportion of BDCA3+ myeloid DCs was lower in obese patients (64.3 ± 26.5%) compared to normal-weight patients (82.7 ± 10.0%, pnormal-weight vs. obesity=0.05) at 2nd FU after LVAD implantation. The analysis of BDCA4+ plasmacytoid DCs revealed a reduced proportion in pre-obese (21.1 ± 9.8%, pnormal-weight vs. pre-obesity=0.01) and obese patients (23.7 ± 10.6%, pnormal-weight vs. obesity=0.05) compared to normal-weight patients (33.1 ± 8.2%) in the 1st FU. T cell analysis showed that CD4+ T cells of obese patients (62.4 ± 9.0%) significantly increased in comparison to pre-obese patients (52.7 ± 10.0%, ppre-obesity vs. obesity=0.05) and CD8+ T cells were lower in obese patients (31.8 ± 8.5%) than in normal-weight patients (42.4 ± 14.2%; pnormal-weight vs. obesity=0.04) at the 3rd FU. Furthermore, we observed significantly reduced proportions of Tregs in pre-obese patients compared to normal-weight and obese patients at 2nd FU (p=0.02) and 3rd FU (p=0.01) after LVAD implantation. Conclusion: This study reported changes of the innate and adaptive immune system of pre-obese and obese compared to normal-weight patients one year after LVAD implantation. DCs and their subsets, CD8+ T cells and Tregs were affected immune cell populations that indicate immunological changes which might increase the incidence of postoperative infection.

Health status analysis is comparable in HM3 patients with different preoperative grades of mitral regurgitation.

BACKGROUND: The guidelines for mechanical circulatory support of the International Society for Heart and Lung Transplantation do not recommend the routine replacement or repair of the mitral valve at the time point of left ventricular assist device (LVAD) implantation. We investigated different parameters of health status including exercise capacity, anxiety and depression after LVAD implantation in patients with different preoperative grades of mitral regurgitation (MR). METHODS: A single-center analysis of health status was performed including 45 patients with HeartMate 3 (HM 3) implantation using the 12-items Short Form Health Survey (SF-12) and the Hospital Anxiety and Depression Score (HADS) questionnaires. The study groups were classified according to echocardiographically defined preoperative grade of MR. The group without severe MR comprised 33 patients; the group with severe MR comprised 12 patients. RESULTS: Demographic and preclinical characteristics as well as LVAD complications such as thrombosis and bleeding events were comparable between LVAD patients with severe and not severe MR (p > 0.05). Severe MR resolved in all patients after LVAD implantation and improved to moderate, mild or no MR in both groups in a period ranging from 6 months until 2 years. The analyses of SF-12 questionnaire revealed that the physical (p = 0.44) and mental health (p = 0.64) was comparable. The grade of anxiety (p = 0.34) and depression (p = 0.44) was comparable between the groups. Exercise capacity measured by the 6 min walk test correlated positively with the SF-12-determined physical health (p < 0.01, r = 0.518) and negatively with the HADS anxiety (p = 0.01, r = -0.399) and depression (p < 0.01, r = -0.570) scores. CONCLUSIONS: Our data showed that the health status is comparable in HM 3 patients with different preoperative MR severities in the post-LVAD period. Preoperative severe MR resolves in the majority of patients early after LVAD implantation and is not associated with concomitant mitral valve repair or replacement at the time of LVAD implantation.

Stroke and pump thrombosis following left ventricular assist device implantation: The impact of the implantation technique.

Objectives: Several studies have shown the potential advantage of less-invasive surgery (LIS) for left ventricular assist device (LVAD) implantation. This study aims to determine the impact of LIS on stroke and pump thrombosis events after LVAD implantation. Methods: Between January 2015 and March 2021, 335 consecutive patients underwent LVAD implantation using either conventional sternotomy (CS) or the LIS technique. Patient characteristics was prospectively collected. All patients were followed up until October 2021. Logistic multivariate regression and propensity-matched analyses were performed to account for confounding factors. Results: A total of 242 patients (F = 32; 13.0%) underwent LVAD implantation with CS and 93 patients (F = 8; 8.6%) with the LIS approach. Propensity matching generated two groups, including 98 patients in the CS group and 67 in the LIS group. Intensive care unit stay for the LIS group patients was significantly shorter than that for the CS group patients [2 (IQR: 2-5) days vs. 4 (IQR: 2-12) days, p < 0.01]. There were no significant differences in the incidence of stroke events (14% in CS vs. 16% in the LIS group; p = 0.6) or in pump thrombosis (6.1% in CS vs. 7.5% in the LIS group; p = 0.8) between the groups. The hospital mortality rate in the matched cohort was significantly lower in the LIS group (7.5% vs. 19%; p = 0.03). However, the 1-year mortality rate showed no significant difference between both groups (24.5% in CS and 17.9% in LIS; p = 0.35). Conclusions: The LIS approach for LVAD implantation is a safe procedure with potential advantage in the early postoperative period. However, the LIS approach remains comparable to the sternotomy approach in terms of postoperative stroke, pump thrombosis, and outcome.

The Impact of Obesity on T and NK Cells after LVAD Implantation.

INTRODUCTION: Infections are a major problem after left ventricular assist device (LVAD) implantation that affects morbidity, mortality, and the quality of life. Obesity often increases the risk for infection. In the cohort of LVAD patients, it is unknown if obesity affects the immunological parameters involved in viral defense. Therefore, this study investigated whether overweight or obesity affects immunological parameters such as CD8+ T cells and natural killer (NK) cells. METHODS: Immune cell subsets of CD8+ T cells and NK cells were compared between normal-weight (BMI 18.5-24.9 kg/m2, n = 17), pre-obese (BMI 25.0-29.9 kg/m2, n = 24), and obese (BMI ≥30 kg/m2, n = 27) patients. Cell subsets and cytokine serum levels were quantified prior to LVAD implantation and at 3, 6, and 12 months after LVAD implantation. RESULTS: At the end of the first postoperative year, obese patients (31.8% ± 2.1%) had a lower proportion of CD8+ T cells than normal-weight patients (42.4% ± 4.1%; p = 0.04), and the percentage of CD8+ T cells was negatively correlated with BMI (p = 0.03; r = -0.329). The proportion of circulating NK cells increased after LVAD implantation patients in normal-weight (p = 0.01) and obese patients (p < 0.01). Patients with pre-obesity showed a delayed increase (p < 0.01) 12 months after LVAD implantation. Further, obese patients showed an increase in the percentage of CD57+ NK cells after 6 and 12 months (p = 0.01) of treatment, higher proportions of CD56bright NK cells (p = 0.01), and lower proportions of CD56dim/neg NK cells (p = 0.03) 3 months after LVAD implantation than normal-weight patients. The proportion of CD56bright NK cells positively correlated with BMI (p < 0.01, r = 0.403) 1 year after LVAD implantation. CONCLUSIONS: This study documented that obesity affects CD8+ T cells and subsets of NK cells in patients with LVAD in the first year after LVAD implantation. Lower proportions of CD8+ T cells and CD56dim/neg NK cells and higher proportion of CD56bright NK cells were detected in obese but not in pre-obese and normal-weight LVAD patients during the first year after LVAD implantation. The induced immunological imbalance and phenotypic changes of T and NK cells may influence viral and bacterial immunoreactivity.

The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIbα Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months.

Non-surgical bleeding (NSB) remains the most critical complication in patients under left ventricular assist device (LVAD) support. It is well known that blood exposed to high shear stress results in platelet dysfunction. Compared to patients without NSB, decreased surface expression of platelet receptor GPIbα was observed in LVAD patients with NSB. In this study, we aimed to compare the expression level of glycoprotein (GP)Ib-IX-V platelet receptor complex in HeartMate 3 (HM 3) patients with and without bleeding complications to investigate the alterations of the platelet transcriptomic profile on platelet damage and increased bleeding risk. Blood samples were obtained from HM 3 patients with NSB (bleeder group, n = 27) and without NSB (non-bleeder group, n = 55). The bleeder group was further divided into patients with early NSB (bleeder ≤ 3 mo, n = 19) and patients with late NSB (bleeder > 3 mo, n = 8). The mRNA and protein expression of GPIbα, GPIX and GPV were quantified for each patient. Non-bleeder, bleeder ≤ 3 mo and bleeder > 3 mo were comparable regarding the mRNA expression of GPIbα, GPIX and GPV (p > 0.05). The protein analysis revealed a significantly reduced expression level of the main receptor subunit GPIbα in bleeders ≤ 3 mo (p = 0.04). We suggest that the observed reduction of platelet receptor GPIbα protein expression in patients who experienced their first bleeding event within 3 months after LVAD implantation may influence platelet physiology. The alterations of functional GPIbα potentially reduce the platelet adhesion capacities, which may lead to an impaired hemostatic process and the elevated propensity of bleeding in HM 3 patients.

Decreased Platelet Specific Receptor Expression of P-Selectin and GPIIb/IIIa Predict Future Non-Surgical Bleeding in Patients after Left Ventricular Assist Device Implantation.

Non-surgical bleeding (NSB) is one of the major clinical complications in patients under continuous-flow left ventricular assist device (LVAD) support. The increased shear stress leads to an altered platelet receptor composition. Whether these changes increase the risk for NSB is unclear. Thus, we compared the platelet receptor composition of patients with (bleeder group, n = 18) and without NSB (non-bleeder group, n = 18) prior to LVAD implantation. Blood samples were obtained prior to LVAD implantation and after bleeding complications in the post-implant period. Platelet receptor expression of GPIbα, GPIIb/IIIa, P-selectin and CD63 as well as intra-platelet oxidative stress levels were quantified by flow cytometry. Bleeders and non-bleeders were comparable regarding clinical characteristics, von Willebrand factor diagnostics and the aggregation capacity before and after LVAD implantation (p > 0.05). LVAD patients in the bleeder group suffered from gastrointestinal bleeding (33%; n = 6), epistaxis (22%; n = 4), hematuria or hematoma (17%; n = 3, respectively) and cerebral bleeding (11%; n = 2). Prior to LVAD implantation, a restricted surface expression of the platelet receptors P-selectin and GPIIb/IIIa was observed in the bleeder group (P-selectin: 7.2 ± 2.6%; GPIIb/IIIa: 26,900 ± 13,608 U) compared to non-bleeders (P-selectin: 12.4 ± 8.1%, p = 0.02; GPIIb/IIIa: 36,259 ± 9914 U; p = 0.02). We hypothesized that the reduced platelet receptor expression of P-selectin and GPIIb/IIIa prior to LVAD implantation may be linked to LVAD-related NSB.

Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated Cardiomyopathy.

Disturbances in the ubiquitin proteasome system, and especially changes of the E3 ligases, are subjects of interest when searching for causes and therapies for cardiomyopathies. The aim of this study was to clarify whether the myostatin/AKT/forkhead box O (FOXO) pathway, which regulates the expression of the E3 ligases muscle atrophy F-box gene (MAFbx) and muscle ring-finger protein-1 (MuRF1), is changed in dilated cardiomyopathy of ischemic origin (IDCM) and dilated cardiomyopathy of non-ischemic origin (NIDCM). The mRNA and protein expression of myostatin, AKT, FOXO1, FOXO3, MAFbx and MuRF1 were quantified by real-time polymerase chain reaction and ELISA, respectively, in myocardial tissue from 26 IDCM and 23 NIDCM patients. Septal tissue from 17 patients undergoing Morrow resection served as a control. MAFbx and FOXO1 mRNA and protein expression (all p < 0.05), AKT mRNA (p < 0.01) and myostatin protein expression (p = 0.02) were decreased in NIDCM patients compared to the control group. Apart from decreases of AKT and MAFbx mRNA expression (both p < 0.01), no significant differences were detected in IDCM patients compared to the control group. Our results demonstrate that the myostatin/AKT/FOXO pathway is altered in NIDCM but not in IDCM patients. FOXO1 seems to be an important drug target for regulating the expression of MAFbx in NIDCM patients.

Wearable cardioverter defibrillator multicentre experience in a large cardiac surgery cohort at transient risk of sudden cardiac death.

OBJECTIVES: The wearable cardioverter defibrillator (WCD) is an established, safe, effective solution, protecting patients at risk of sudden cardiac death. We specifically investigated WCD use in cardiac surgery patients since data for this patient group are rare. METHODS: Retrospective data analysis in 10 German cardiac surgery centres was performed. Cardiac surgery patients with left ventricular ejection fraction (LVEF) ≤35% or after implantable cardioverter defibrillator (ICD) explantation who received WCD between 2010 and 2020 were assessed using LifeVest Network data. RESULTS: A total of 1168 patients with a median age of 66 years [interquartile range (IQR) 57-73] were enrolled; 87% were male. Clinical indications included coronary artery bypass grafting (43%), valve surgery (16%), combined coronary artery bypass graft/valve surgery (15%), ICD explantation (24%) and miscellaneous (2%). The median wear time of WCD was 23.4 h/day (IQR 21.7-23.8). A total of 106 patients (9.1%) exhibited ventricular tachycardia. A total of 93.2% of episodes occurred within the first 3 months. Eighteen patients (1.5%) received 26 adequate shocks. The inadequate shock rate was low (8 patients, 0.7%). LVEF improved from a median of 28% (IQR 22-32%) before WCD prescription to 35% (IQR 28-42%) during follow-up. Excluding ICD explant patients, 37% of patients received an ICD. CONCLUSIONS: The risk of sudden cardiac death is substantial within the first 3 months after cardiac surgery. Patients were protected effectively by WCD. Due to significant LVEF improvement, the majority did not require ICD implantation after WCD use. Compliance was high despite sternotomy. This multicentre experience confirms existing data regarding effectiveness, safety and compliance. Therefore, WCD should be considered in cardiac surgery patients with severely reduced LVEF.

Long-Term Follow-Up of Mechanical Circulatory Support in Peripartum Cardiomyopathy (PPCM) Refractory to Medical Management: A Multicenter Study.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare, life-threatening form of heart disease, frequently associated with gene alterations and, in some cases, presenting with advanced heart failure. Little is known about ventricular assist device (VAD) implantation in severe PPCM cases. We describe long-term follow-up of PPCM patients who were resistant to medical therapy and received mechanical circulatory support or heart transplant. METHODS AND RESULTS: A total of 13 patients were included with mean follow-up of eight years. Mean age of PPCM onset was 33.7 ± 7.7 years. All patients were initially treated with angiotensin-converting enzyme inhibitors and beta-blockers, and four received bromocriptine. Overall, five patients received VADs (three biventricular, two isolated left ventricular) at median 27 days (range: 3 to 150) following childbirth. Two patients developed drive line infection. Due to the short support time, none of those patients had a stroke or VAD thrombosis. In total, five patients underwent heart transplantation, of which four previously had implanted VADs. Median time to transplantation from PPCM onset was 140 days (range: 43 to 776), and time to transplantation from VAD implantation were 7, 40, 132, and 735 days, respectively. All patients survived until most recent follow up, with the exception of one patient who died following unrelated abdominal surgery two years after PPCM recovery. CONCLUSIONS: In patients with severe, life-threatening PPCM refractory to medical management, mechanical circulatory support with or without heart transplantation is a safe therapeutic option.

Everolimus-Induced Immune Effects after Heart Transplantation: A Possible Tool for Clinicians to Monitor Patients at Risk for Transplant Rejection.

BACKGROUND: Patients treated with an inhibitor of the mechanistic target of rapamycin (mTORI) in a calcineurin inhibitor (CNI)-free immunosuppressive regimen after heart transplantation (HTx) show a higher risk for transplant rejection. We developed an immunological monitoring tool that may improve the identification of mTORI-treated patients at risk for rejection. METHODS: Circulating dendritic cells (DCs) and regulatory T cells (Tregs) were analysed in 19 mTORI- and 20 CNI-treated HTx patients by flow cytometry. Principal component and cluster analysis were used to identify patients at risk for transplant rejection. RESULTS: The percentages of total Tregs (p = 0.02) and CD39+ Tregs (p = 0.05) were higher in mTORI-treated patients than in CNI-treated patients. The principal component analysis revealed that BDCA1+, BDCA2+ and BDCA4+ DCs as well as total Tregs could distinguish between non-rejecting and rejecting mTORI-treated patients. Most mTORI-treated rejectors showed higher levels of BDCA2+ and BDCA4+ plasmacytoid DCs and lower levels of BDCA1+ myeloid DCs and Tregs than mTORI non-rejectors. CONCLUSION: An mTORI-based immunosuppressive regimen induced a sufficient, tolerance-promoting reaction in Tregs, but an insufficient, adverse effect in DCs. On the basis of patient-specific immunological profiles, we established a flow cytometry-based monitoring tool that may be helpful in identifying patients at risk for rejection.

Differential Regulation of Myocardial E3 Ligases and Deubiquitinases in Ischemic Heart Failure.

The pathological changes of ubiquitination and deubiquitination following myocardial infarction (MI) and chronic heart failure (CHF) have been sparsely examined. We investigated the expression of muscle-specific E3 ubiquitin ligases and deubiquitinases in MI and CHF. Therefore, mice were assigned to coronary artery ligation for 3 days or 10 weeks as well as for sham operation (each n = 10). Expression of E3 ligases (MAFBX, MURF1, CHIP, ITCH, MDM2) and deubiquitinases (A20, CYLD, UCH-L1, USP14, USP19) was determined. After MI and in CHF, the mRNA expression of MURF1, CHIP and MDM2 (all p < 0.05) was decreased. Protein expression analyses revealed that ITCH expression decreased in CHF (p = 0.01), whereas MDM2 expression increased in MI (p = 0.02) and decreased in CHF (p = 0.02). Except for USP19 mRNA expression that decreased at 3 days and 10 weeks (both p < 0.01), the expression of other deubiquitinases remained unaffected after MI and CHF. The expression of myocardial E3 ligases is differentially regulated following MI, raising the question of whether an upstream regulation exists that is activated by MI for tissue protection or whether the downregulation of E3 ligases enables myocardial hypertrophy following MI.

Sex Differences in Clinical Course and Intensive Care Unit Admission in a National Cohort of Hospitalized Patients with COVID-19.

Males have a higher risk for an adverse outcome of COVID-19. The aim of the study was to analyze sex differences in the clinical course with focus on patients who received intensive care. Research was conducted as an observational retrospective cohort study. A group of 23,235 patients from 83 hospitals with PCR-confirmed infection with SARS-CoV-2 between 4 February 2020 and 22 March 2021 were included. Data on symptoms were retrieved from a separate registry, which served as a routine infection control system. Males accounted for 51.4% of all included patients. Males received more intensive care (ratio OR = 1.61, 95% CI = 1.51-1.71) and mechanical ventilation (invasive or noninvasive, OR = 1.87, 95% CI = 1.73-2.01). A model for the prediction of mortality showed that until the age 60 y, mortality increased with age with no substantial difference between sexes. After 60 y, the risk of death increased more in males than in females. At 90 y, females had a predicted mortality risk of 31%, corresponding to males of 84 y. In the intensive care unit (ICU) cohort, females of 90 y had a mortality risk of 46%, equivalent to males of 72 y. Seventy-five percent of males over 90 died, but only 46% of females of the same age. In conclusion, the sex gap was most evident among the oldest in the ICU. Understanding sex-determined differences in COVID-19 can be useful to facilitate individualized treatments.

No Association between Clinical Periodontal Conditions and Microbiological Findings on Driveline of Patients with Left-Ventricular Assist Devices (LVAD).

The aim of this retrospective study was to investigate whether there would be an association between periodontal disease parameters and positive bacterial findings at the driveline of patients with a left ventricular assist device (LVAD). Patients with an LVAD, who underwent a full oral and microbiological examination between 2016 and 2018, were included. During oral examination, periodontitis severity (stage and grade) and the periodontal inflamed surface area (PISA) were evaluated. A microbiological analysis was performed from swabs of the driveline, whereby different bacterial species were cultivated and analyzed. A total of 73 patients were included in the current study. The majority of participants (80.8%) had at least one positive bacterial finding during the study period. Most patients had a periodontitis stage of III-IV (80.9%). The determined PISA of the total group was 284.78 ± 352.29 mm2. No associations were found between the periodontal disease parameters and the bacterial findings in general, the bacterial findings on the day of oral examination or the bacterial findings 12 months prior to/after the oral examination (p > 0.05). Periodontitis is not associated with cultivated microbiological findings at the driveline of patients with an LVAD and thus appears not to be a risk indicator for driveline colonization. Nevertheless, the high periodontal burden in LVAD patients underlines the need for their improved periodontal care.

Minimally invasive ventricular assist device implantation.

Durable mechanical circulatory support (MCS) systems are established therapy option in patients with end-stage heart failure, with increasing importance during the last years due to donor organ shortage. Left ventricular assist devices (LVADs) are traditionally implanted through median sternotomy (MS). However, improvement in the pump designs during the last years led to evolvement of new surgical approaches that aim to reduce the invasiveness of the procedure. Numerous reports and studies have shown the viability and possible advantages of less-invasive approach compared to the sternotomy approach. The less invasive implant strategies for LVADs, while vague in definition, are characterized by minimizing surgical trauma and if possible, cardio-pulmonary bypass related complications. Usually it involves minimizing or completely avoiding sternal trauma, avoiding heart luxation while simultaneously leaving the major part of pericardium intact. There is no consensus between the centers regarding the ideal approach for LVAD implantation. Some centers, like our center, perform by default VAD implantation using less invasive approach in almost all patients and some centers use only sternotomy approach. The aim of this review article is to shed light on the currently available less invasive options of LVAD implantation, with particular focus on the centrifugal pumps, and their possible advantages compared to traditional sternotomy approach.

Device-induced platelet dysfunction in patients after left ventricular assist device implantation.

BACKGROUND: Non-surgical bleeding (NSB) is a major complication after left ventricular assist device (LVAD) implantation. It has been reported that non-physiological shear stress caused by LVADs could alter platelet receptor expression, which leads to bleeding disorders caused by coagulation dysfunctions. OBJECTIVES: Because bleeding diathesis could be multifactorial, we focused on the combined characterization of platelet receptor expression patterns and oxidative stress to compare patients with NSB and patients without coagulation disorder in a monocentric, prospective study. METHODS: Blood samples were obtained from LVAD patients with NSB (bleeder group, n = 19) and without NSB (non-bleeder group, n = 20). The platelet receptors platelet endothelial cell adhesion molecule-1 (PECAM-1), glycoprotein (GP)Ibα, P-selectin, CD63, and GPIIb/IIIa, as well as the production of intraplatelet reactive oxygen species (ROS) were quantified by flow cytometry. Aggregation capacity was evaluated by aggregometry. RESULTS: The surface expression level of P-selectin and GPIbα on platelets was decreased in bleeders (P-selectin: 465 ± 72 U; GPIbα: 435 ± 41 U) compared to non-bleeders (P-selectin: 859 ± 115 U, P < .01; GPIbα: 570 ± 49 U, p = .04). Additionally, the mean fluorescence intensity of ADP-stimulated P-selectin and PECAM-1 expressing platelets were reduced in bleeders (P-selectin: 944 ± 84 U; PECAM-1: 6722 ± 419 U) compared to non-bleeders (P-selectin: 1269 ± 130 U, P = .04; PECAM-1: 8542 ± 665 U, P = .03). Bleeders showed a higher amount of ROS formation in platelets (88.0 ± 2.6%) than non-bleeders (81.5 ± 2.1%, P = .05). CONCLUSIONS: These findings suggested that changes of three platelet receptors (GPIbα, P-selectin, and PECAM-1) and elevated oxidative stress may play a role in patients with bleeding complications following LVAD implantation. These results might help to explain the high incidence of spontaneous hemorrhage during LVAD support through an altered platelet function.

Validation of the VT-LVAD score for prediction of late VAs in LVAD recipients.

OBJECTIVES: This study sought to validate the performance of the VT-LVAD risk model in predicting late ventricular arrhythmias (VAs) in patients after left ventricular assist device (LVAD) implantation. BACKGROUND: The need for implantable cardioverter-defibrillator (ICD)-implantation in LVAD recipients is not well studied. A better selection of the patients with high risk for late VAs could lead to a more targeted ICD-implantation or replacement. METHODS: The study evaluated the performance of the VT-LVAD prognostic score (VAs prior LVAD, no ACE-inhibitor in medication, heart failure duration > 12 months, early VAs post-LVAD implantation, atrial fibrillation prior LVAD, idiopathic dilated cardiomyopathy) for the endpoint of the occurrence of late VAs in 357 LVAD patients in Heart Centre of Leipzig. RESULTS: From the initial 460 patients, 357 (age: 58 ± 10 years; left ventricular ejection fraction: 20 ± 6%; HeartWare: 50%; HeartMate III: 42%) were assigned to four risk groups according to their VT-LVAD score varying from low risk to very high risk. After 25 months, late VAs occurred in 130 patients. The VT-LVAD score was an independent predictor of late VAs (multivariate analysis; p = < .001; goodness-of-tip p = .347; odds ratio: 4.8). While there was no statistically significant difference between the low- and intermediate-risk group, risk stratification for patients with high risk and very high risk performed more accurately (pairwise comparison p = .005 and p < .001, respectively). CONCLUSIONS: The VT-LVAD score predicted accurately the occurrence of late VAs in high-risk LVAD recipients in a large external cohort of LVAD recipients supporting its utility for more targeted ICD implantations.

International experience using a durable, centrifugal-flow ventricular assist device for biventricular support.

BACKGROUND: Heart transplantation is limited by the scarcity of suitable donors. Patients with advanced biventricular failure may require biventricular support to provide optimal cardiac output and end-organ perfusion. We highlight the outcomes of using the HeartWare HVAD System (HVAD) in a biventricular configuration. METHODS: This retrospective study included patients implanted with HVAD as a biventricular assist device (BiVAD) between 2009 and 2017 at 12 participating centers. When used as a right ventricular assist device (VAD) (RVAD), the HVAD can be attached to the right ventricle (RV) or the right atrium (RA). Kaplan-Meier survival estimates were calculated comparing the 2 RVAD implant locations. Comparisons were also made between the timing of RVAD implantation (primary vs staged) on adverse event (AE) profiles and survival. RESULTS: Among the 93 patients who were implanted with a HVAD BiVAD, Kaplan-Meier survivals at 1-year and 2-year were 56% and 47%, respectively. Survival was independent of the location of the HVAD RVAD implant or whether there was an interval between left VAD and RVAD implantation. The most common AEs were bleeding (35.5%), infection (25.8%), and respiratory failure (20.4%). CONCLUSIONS: This study illustrated similar survival in patients receiving a primary or staged HVAD BiVAD implant at 1 year and 2 years. This study also established that the locations of the RVAD implant (RV or RA) result in similar AE profiles.

Clinical characteristics and outcomes of patients with adult congenital heart disease listed for heart and heart‒lung transplantation in the Eurotransplant region.

BACKGROUND: The therapeutic success in patients with congenital heart disease (CHD) leads to a growing number of adults with CHD (adult CHD [ACHD]) who develop end-stage heart failure. We aimed to determine patient characteristics and outcomes of ACHD listed for heart transplantation. METHODS: Using data from all the patients with ACHD in 20 transplant centers in the Eurotransplant region from 1999 to 2015, we analyzed patient characteristics, waiting list, and post-transplantation outcomes. RESULTS: A total of 204 patients with ACHD were listed during the study period. The median age was 38 years, and 62.3% of the patients were listed in high urgency (HU), and 37.7% of the patients were in transplantable (T)-listing status. A total of 23.5% of the patients died or were delisted owing to clinical worsening, and 75% of the patients underwent transplantation. Median waiting time for patients with HU-listing status was 4.18 months and with T-listing status 9.07 months. There was no difference in crude mortality or delisting between patients who were HU status listed and T status listed (p = 0.65). In multivariable regression analysis, markers for respiratory failure (mechanical ventilation, hazard ratio [HR]: 1.41, 95% CI: 1.11-1.81, p = 0.006) and arrhythmias (anti-arrhythmic medication, HR: 1.42, 95% CI: 1.01-2.01, p = 0.044) were associated with a higher risk of death or delisting. In the overall cohort, post-transplantation mortality was 26.8% after 1 year and 33.4% after 5 years. CONCLUSIONS: Listed patients are at high risk of death without differences in the urgency of listing. Respiratory failure requiring invasive ventilation and possibly arrhythmias requiring anti-arrhythmic medication indicate worse outcomes on waiting list.

Heart Disease in Adult Syrian Refugees: Experience at Jordan University Hospital.

BACKGROUND: Since 2011, 1.26 million Syrians have immigrated to Jordan, increasing demands on Healthcare service. Information about cardiovascular disease (CVD) in Syrian refugees in general, and specifically in Jordan, is unknown. OBJECTIVES: The study aimed to describe CVD in Syrian refugee adults who were referred to Jordan University Hospital (JUH) in terms of diagnosis, presentation, outcome, sources of funding for treatment, and to follow these patients after their discharge. METHODS: From January 2012 to October 2016, retrospective analysis was performed on the data of Syrian patients who were referred to JUH. This study describes the diagnoses, treatment, and outcome. It also discusses the funding sources; a follow-up was conducted until January 2017. RESULTS: There were 969 patients referred to JUH with CVD; median age was 56 years, 686 (72.2%) of them were males and 283 (27.8%) were females. Of the patients, 584 had hypertension (60%), 308 (31%) had diabetes mellitus, 281 (29.0%) suffered from dyslipidemia, and 237 were smokers (24%). There were 69.6% who had coronary artery disease (CAD) and 20 patients (2%) had valvular heart disease. Treatment was offered to 489 patients (49.5%), but only 322 (65.8% of treatment offered and 33.2% of referrals) of them received the intended treatment. Mortality rate was 3% and loss of follow-up was 49.2%. Funding for procedures mostly came from the Jordanian Health Aid Organization, the United Nations, NGOs, and charities. Sixty-four (13.3% of referred) patients were denied any funding during the time frame of this study. CONCLUSIONS: CVD is a major issue for both Syrian refugee patients and the Jordanian healthcare system. CAD and classic cardiovascular risk factors (specifically arterial hypertension, diabetes, and dyslipidemia) are most common in this specific population. Inadequate primary healthcare, suboptimal living conditions, lack of funding, and loss of patient contact are among the major challenges facing this vulnerable population.