Long-term predictors of morbidity and mortality in patients following LVAD replacement.

BACKGROUND: As heart transplant guidelines evolve, the clinical indication for 73% of durable left ventricular assist device (LVAD) implants is now destination therapy. Although completely magnetically levitated LVAD devices have demonstrated improved durability relative to previous models, LVAD replacement procedures are still required for a variety of indications. Thus, the population of patients with a replaced LVAD is growing. There is a paucity of data regarding the outcomes and risk factors for those patients receiving first-time LVAD replacements. METHODS: The study cohort consisted of all consecutive patients between 2006 and 2020 that received a first-time LVAD replacement at a single institution. Preoperative clinical and laboratory variables were collected retrospectively. The primary endpoint was death or need for an additional LVAD replacement. Data were subjected to Kaplan-Meier, univariate, and multivariate Cox hazard ratio analyses. RESULTS: In total, 152 patients were included in the study, of which 101 experienced the primary endpoint. On multivariate analysis, patients receiving HeartMate 3 (HM3) LVADs as the replacement device showed superior outcomes (HR 0.15, 95% CI 0.065-0.35, p < 0.0001). Independent risk factors for death or need for additional replacement included preoperative extracorporeal membrane oxygenation (ECMO) (HR 4.44, 95% CI 1.87-14.45, and p = 0.00042), increased number of sternotomies (HR 5.20, 95% CI 1.87-14.45, and p = 0.0016), and preoperative mechanical ventilation (HR 1.98, 95% CI 1.01-3.86, and p = 0.045). CONCLUSIONS: Replacement with HM3 showed superior outcomes compared to all other pump types when controlling for both initial pump type and other independent predictors of death or LVAD replacement. Preoperative ECMO, mechanical ventilation, and multiple sternotomies also increased the odds for death or the need for subsequent replacement.

The Clinical SYNTAX score predicts survival better than the SYNTAX score in coronary revascularization.

BACKGROUND: The Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) trial showed that the SYNTAX score (SS) is a useful tool for customizing revascularization treatment for patients with multivessel coronary disease. In the past decade, the Clinical SS (CSS) has emerged as a comprehensive tool. This novel tool considers the SS as well as patient clinical parameters such as age, creatinine clearance, and ejection fraction, which were shown to be relevant for patient prognosis. Thus, in the current work we set out to compare the survival predictive values of the SS versus the CSS and their future application in real-world implementation of the revascularization guidelines. METHODS: This study was a subanalysis of data collected in a prospective national registry in Israel that enrolled consecutive patients with left main and/or 2- to 3-vessel coronary artery disease involving the proximal or mid-left anterior descending artery; the MULTI-vessel Coronary Artery Disease (MULTICAD). The revascularization method was chosen by the physicians taking care of the patients at each hospital and the patients were followed for 5 years. Patients were categorized according to their SS, the CSS, and their revascularization method (primary coronary intervention [PCI] vs coronary artery bypass grafting [CABG]) and patient survival were compared. RESULTS: A total of 585 patients were enrolled in the study and were followed for 5 years. The median CSS was 27, with 288 patients showing a CSS ≥27, with a mean CSS of 47.85 and a mean SS of 29.05. At 3 and 5 years post-treatment, the CSS ≥27 group had a lower survival probability, CSS ≥27 was associated with a lower survival probability among patients who underwent PCI compared with those who underwent CABG. More specifically, the high-CSS CABG group had a 5-year mortality rate of 16.8%, whereas the high-CSS PCI group had a 5-year mortality rate of 32.2%. In a comparison of SS with CSS for the 5-year mortality outcome prediction, CSS was superior to SS with a higher area under the curve. CONCLUSIONS: This prospective registry of real-world revascularization strategies in patients with multivessel disease showed that CSS is a better predictive tool of postrevascularization survival than SS. Moreover, it showed that surgical revascularization in patients with CSS ≥27 is associated with better all-cause mortality outcome after CABG as compared with after PCI. This attests to the need for a score that considers clinical parameters in a real-world scenario.

Ubiquitin Proteasome System Role in Diabetes-Induced Cardiomyopathy.

This study investigated modifications to the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. db/db mice heart tissues were compared with WT mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. The findings unveiled a distinctive gene profile in the hearts of db/db mice with decreased levels of nppb mRNA and increased levels of Myh7, indicating potential cardiac dysfunction. The mRNA levels of USP18 (deubiquitinating enzyme), PSMB8, and PSMB9 (proteasome ß-subunits) were down-regulated in db/db mice, while the mRNA levels of RNF167 (E3 ligase) were increased. Corresponding LMP2 and LMP7 proteins were down-regulated in db/db mice, and RNF167 was elevated in Adult diabetic mice. The reduced expression of LMP2 and LMP7, along with increased RNF167 expression, may contribute to the future cardiac deterioration commonly observed in diabetes. This study enhances our understanding of UPS imbalances in the hearts of diabetic mice and raises questions about the interplay between the UPS and other cellular processes, such as autophagy. Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets.

A single center Israeli experience in pregnancy post lung transplantation: Feasibility of successful two or more full-term pregnancies in individual lung transplant recipients.

INTRODUCTION: Female lung transplant recipients (LTRs) of reproductive age are increasingly considering pregnancy due to advances in post-transplant management and improved survival. We report our experience with pregnancy in LTRs, with an emphasis on two or more successful full-term pregnancies in individual transplant recipients. METHODS: We conducted a retrospective analysis of pregnancies in LTRs at our transplant center and collected maternal and fetal outcomes. RESULTS: In our patient cohort, eight female LTRs conceived a total of 17 pregnancies, resulting in 13 newborns, 12 at full term, and 11 with a birth weight > 2.5 kg. Three of the LTRs had two or more successful full-term pregnancies. LTRs required a significant tacrolimus dose increase to maintain target trough levels during pregnancy. Six recipients are currently clinically stable and active, three with lung function comparable to pre-pregnancy values, and three with evidence of chronic lung allograft dysfunction (CLAD), but stable lung function. Two of the eight LTRs died subsequent to childbirth secondary to chronic respiratory failure due to CLAD, at a mean of 11 years post-transplantation and a mean of 4.5 years after childbirth. CONCLUSION: Pregnancy following lung transplantation is feasible and can be achieved with acceptable maternal and newborn outcomes. Importantly, LTRs can successfully have two or more full-term pregnancies.

Exergaming in patients with a left ventricular assist device: a feasibility study.

AIMS: Exercise games (exergames) have been recently proposed as a mode of facilitating physical activity in patients with chronic diseases. Although patients supported with left ventricular assist devices (LVADs) benefit from physical activity, specific LVAD-related issues hinder their ability to exercise properly. The objective of this study was to assess the feasibility and safety of exergaming in LVAD-supported patients. METHODS AND RESULTS: Eleven LVAD-supported patients were enrolled in a 4 week exergaming programme using Nintendo Wii console with five sport games. Patients were instructed to play for 30 min a day, 5 days a week. Data on exercise capacity and exergaming were collected by using the 6 min walk test (6MWT) and a daily self-report diary, respectively. Feasibility of using the console and its safety was assessed by a semi-structured patient interview. Quality of life was assessed by the Minnesota Living with Heart failure Questionnaire (MLHFQ) and the Cantril's Ladder of Life. Safety was assessed by patient's report in interview and diary. The study group consisted of 10 male patients and 1 female patient, mean age of 67 ± 7 years, of whom 10 were supported with the HeartMate 3 LVAD for a median of 10 (interquartile range 3, 21) months. Baseline exercise capacity assessed by the 6MWT ranged from 240 to 570 m (mean 448 ± 112). After 4 weeks of exergaming, 6MWT distance increased from a mean of 448 ± 112 (evaluated in six patients) to 472 ± 113 m (P = 0.023). Patients' Cantril's Ladder of Life score improved numerically from an average of 6.13 to 7.67, as did their MLHFQ score from 45.9 ± 27 to 38.7 ± 18, with higher and lower scores, respectively, reflecting higher quality of life. No specific LVAD-related safety issues regarding exergaming were reported. CONCLUSIONS: Exergaming was found to be a safe and feasible mode for encouraging physical activity in LVAD-supported patients and carries a potential for improving exercise capacity and quality of life in these patients. Larger scale studies are warranted to further investigate the effect of exergaming in this patient population.

Prognostic Significance of the N-Terminal Pro-B-Type Natriuretic Peptide in Lung Transplant Candidates on the Waiting List.

We investigated the prognostic significance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in lung transplant candidates, in a retrospective single-center study. Data regarding various baseline characteristics and all-cause mortality were collected for 205 lung transplant candidates placed on waitlist for transplantation from November 2017 to December 2019. Associations of NT-proBNP levels with baseline characteristics and mortality were analyzed. Results showed NT-proBNP values correlated positively with age, forced vital capacity, mean pulmonary artery pressure (MPAP), and pulmonary capillary wedge pressure; and negatively with diffusing lung capacity for carbon monoxide and cardiac index. The optimal cut-off of NT-proBNP for predicting MPAP levels > 35 mmHg was 251 pg/mL; with 58.1% sensitivity, 85.7% specificity, 45.0% positive predictive value, and 91.0% negative predictive value. During a median follow-up period of 2.2 years, 97 patients underwent lung transplantation, 42 died waiting for donation, and 66 were alive and still waiting for transplantations. On multivariate analysis, higher NT-proBNP levels were strongly associated with increased mortality among waitlisted lung transplant candidates (HR 1.49, 95% CI 1.10−2.03, p = 0.01). In conclusion NT-proBNP can predict mortality among waitlisted lung transplant candidates. Lower levels of NT-proBNP can preclude severe pulmonary artery hypertension. Assessment of NT-proBNP may improve risk stratification among lung transplant candidates.

Right and left ventricular assist devices are an option for bridge to heart transplant.

Background: Patients with a left ventricular assist device with right ventricular failure are prioritized on the heart transplant waitlist; however, their post-transplant survival is less well characterized. We aimed to determine whether pretransplant right ventricular failure affects postoperative survival in patients with a left ventricular assist device as a bridge to transplant. Methods: We performed a retrospective review of the 2005-2018 Organ Procurement and Transplantation Network/United Network for Organ Sharing registry for candidates aged 18 years or more waitlisted for first-time isolated heart transplantation after left ventricular assist device implantation. Candidates were stratified on the basis of having right ventricular failure, defined as the need for right ventricular assist device or intravenous inotropes. Baseline demographic and clinical characteristics were compared among the 3 groups, and post-transplant survival was assessed. Results: Our cohort included 5605 candidates who met inclusion criteria, including 450 patients with right ventricular failure, 344 patients with a left ventricular assist device and intravenous inotropes as a bridge to transplant, 106 patients with a left ventricular assist device and right ventricular assist device, and 5155 patients with a left ventricular assist device as a bridge to transplant without the need for right side support. Compared with patients without right ventricular failure, patients with a left ventricular assist device as a bridge to transplant with right ventricular failure were younger (median age 51 years, 55 vs 56 years, P < .001) and waited less time for organs (median 51 days, 93.5 vs 125 days, P < .001). These patients also had longer post-transplant length of stay (median 18 days, 20 vs 16 days, P < .001). Right ventricular failure was not associated with decreased post-transplant long-term survival on unadjusted Kaplan-Meier analysis (P = .18). Neither preoperative right ventricular assist device nor intravenous inotropes independently predicted worse survival on multivariate Cox proportional hazards analysis. However, pretransplant liver dysfunction (total bilirubin >2) was an independent predictor of worse survival (hazard ratio, 1.74; 95% confidence interval, 1.39-2.17; P < .001), specifically in the left ventricular assist device group and not in the left ventricular assist device + right ventricular assist device/intravenous inotropes group. Conclusions: Patients with biventricular failure are prioritized on the waiting list, because their critical pretransplant condition has limited impact on their post-transplant survival (short-term effect only); thus, surgeons should be confident to perform transplantation in these severely ill patients. Because liver dysfunction (a surrogate marker of right ventricular failure) was found to affect long-term survival in patients with a left ventricular assist device, surgeons should be encouraged to perform transplantation in these severely ill patients after a recipient's optimization by inotropes or a right ventricular assist device because even when the bilirubin level is elevated in these patients (treated with right ventricular assist device/inotropes), their long-term survival is not affected. Future studies should assess recipients' optimization before organ acceptance to improve long-term survival.

Combined mechanical circulatory support for ventricular fibrillation in left ventricular assist device patient.

Ventricular fibrillation, a life-threatening ventricular arrhythmia, may result in pulselessness, loss of consciousness and sudden cardiac death. In this case report, we describe our experience in managing a 54-year-old man with HeartMate3 left ventricular assist device (LVAD) as a bridge to transplantation due to dilated non-ischemic cardiomyopathy, presenting with incessant ventricular arrhythmia for 35 days despite multiple attempts to restore normal rhythm with external direct current cardioversion and anti-arrhythmic medications. The patient remained stable in ventricular arrhythmia with no progression to asystole, but hemodynamic collapse due to right heart failure occurred in the third week. Combined use of two mechanical circulatory support devices (LVAD with VA ECMO) was needed to achieve haemodynamic and metabolic stability, eventually leading to successful heart transplantation in the index admission. The patient was discharged home 2 weeks after transplantation in good clinical condition.

Heartmate 3 as a bridge to heart transplantation in a patient with congenitally corrected transposition of the great arteries: a case report.

BACKGROUND: We report the first use of Heartmate 3 (HM3) in a Congenitally corrected Transposition of the Great Arteries (ccTGA) as a Systemic Ventricular Assist Device (SVAD) to treat HF. CASE PRESENTATION: A 55 years old man with a Congenitally corrected Transposition of the Great Arteries (ccTGA) a rare condition in which Heart Failure (HF) is a common presentation in adult life and survival without heart transplantation is hardly an option. Systemic Ventricular Assist Device (SVAD) can be an option if an organ does not become available. We present the first ever implantation of HM3 LVAD (Abbott Inc, Chicago IL) implanted to this patient as a bridge to transplantation, demonstrating the safety and feasibility of the procedure. Due to the unique mediastinal configuration, 3D cardiac CT reconstruction should be used for planning the procedure-intra ventricular placement of the inflow as well as mediastinal placemat of the outflow and pump. CONCLUSIONS: This successful first use of HM3 as a SVAD for ccTGA patients, opens a novel treatment option for these patients as a bridge for heart transplant or as definitive treatment.

Improved immunogenicity following the third dose of BNT162b2 mRNA vaccine in heart transplant recipients.

OBJECTIVES: The immunogenicity of two-dose severe acute respiratory syndrome coronavirus 2 vaccine is lower among heart transplant (HTx) recipients, compared with the general population. Our aim was to assess the immunogenicity of a third-dose vaccine in HTx recipients. METHODS: This is a prospective cohort study of HTx recipients who received a third dose of the BNT162b2 vaccine. Immunogenicity was assessed by serum levels of anti-spike immunoglobulin G (S-IgG), taken at baseline and 14-28 days after the third dose. Titres above 50 U/ml were interpreted positive. RESULTS: We Included 42 HTx recipients at a median age of 65 years [interquartile range (IQR) 58-70]. At baseline, the median of 27 days (IQR 13-42) before the third dose and the median titre of the whole group was 18 U/ml (IQR 4-130). Only 14 patients (33%) were S-IgG seropositive. After the third dose, the proportion of seropositive patients increased significantly to 57% (P = 0.05) and the median titre increased significantly to 633 U/ml (IQR 7-6104, P < 0.0001). Younger age at HTx (OR per 1-year decrease 1.07, P = 0.05), low tacrolimus serum level (OR per 1-unit decrease 2.28, P = 0.02), mammalian target of rapamycin use (OR 13.3, P = 0.003), lack of oral steroids use (OR 4.17, P = 0.04) and lack of calcineurin inhibitor use (71% of responders vs 100% non-responders received calcineurin inhibitors, P = 0.01) were predictors of seropositive result after the third dose. However, no significant association was detected following adjustment for baseline S-IgG titre. CONCLUSIONS: Third-dose booster of BNT162b2 vaccine significantly increased immunogenicity among HTx recipients who previously received a two-dose vaccine.

Six-months immunogenicity of BNT162b2 mRNA vaccine in heart transplanted and ventricle assist device-supported patients.

AIMS: To assess the 6 months immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in a population of heart transplanted (HTx) recipients and left ventricular assist device (LVAD)-supported patients. METHODS AND RESULTS: A prospective single-centre cohort study of HTx recipients and LVAD-supported patients who received a two-dose SARSCoV-2 mRNA vaccine (BNT162b2, Pfizer-BioNTech). Whole blood for anti-spike IgG (S-IgG) antibodies were drawn at 6 months after the first vaccine dose. S-IgG data at 6 weeks were available for a subgroup of HTx recipients. S-IgG ≥ 50 AU/mL were interpreted positive. The cohort included 53 HTx recipients and 18 LVAD-supported patients. The median time from HTx or LVAD implantation to the 1st vaccine dose was 90 (IQR 30, 172) months and 22 (IQR 6, 78) months, respectively. The seropositivity rates of S-IgG antibodies and their titre levels in HTx recipients and LVAD-supported patients were 45% and 83% respectively, (P = 0.006), and 35 (IQR 7, 306) AU/mL and 311 (IQR 86, 774) AU/mL, respectively, (P = 0.006). Reduced SARSCoV-2 vaccine immunogenicity in HTx recipients was associated with older age [odds ratio (OR) 0.917 confidence interval (CI 0.871, 0.966), P = 0.011] and with the use of anti-metabolites-based immunosuppressive regimens [OR 0.224 (CI 0.065, 0.777), P = 0.018]. mTOR inhibitors were associated with higher immunogenicity [OR 3.1 (CI 1.01, 9.65), P = 0.048]. Out of 13 HTx recipients who were S-IgG seropositive at 6 weeks after the first vaccine dose, 85% remained S-IgG seropositive at 6 month follow-up. CONCLUSIONS: At 6 months post-vaccination, S-IgG immunogenicity in HTx recipients is low, particularly in older HTx recipients and in those treated with anti-metabolites drugs.

Natural History and Prognosis of Patients with Unrepaired Tricuspid Regurgitation Undergoing Implantation of Left Ventricular Assist Device.

We aimed to describe the natural history of left ventricular assist device (LVAD)-supported patients with preimplantation significant tricuspid regurgitation (TR) in a single-center retrospective analysis of LVAD-implanted patients (2008-2019). TR severity was assessed semiqualitatively using color-Doppler flow: insignificant TR (iTR) was defined as none/mild TR and significant TR (sTR) as ≥moderate TR. Included were 121 LVAD-supported patients of which 53% (n = 64) demonstrated sTR preimplantation. Among patients with pre-LVAD implantation sTR and available echocardiographic data, 55% (n = 26) ameliorated their TR severity grade to iTR during the first-year postsurgery and 55% (n = 17) had iTR at 2-year follow-up. On univariate analysis, predictors for TR severity improvement post-LVAD implantation were preimplant lack of atrial fibrillation, reduced inferior vena cavae diameter, and elevated pulmonary vascular resistance. In patients who failed to improve their TR severity grade, we observed a deterioration in right ventricular (RV) function (pulmonary artery pressure index 2.0 [1.7, 2.9], a decline in RV work index 242 [150, 471] mm Hg·L/m2) and higher loop-diuretics dose requirement. At a median of 21 (IQR 8, 40) months follow-up, clinical LVAD-related complications, heart failure-hospitalizations, and overall survival were similar among patients who improved versus failed to improve their TR severity-grade post-LVAD implantation. In conclusion, LVAD implantation is accompanied by a reduction in TR severity in approximately 50% of patients. In patients who failed to improve their TR severity grade, progressive RV dysfunction was observed. Overall, an isolated LVAD implantation in patients with sTR does not adversely affect survival.

Sustained results of robotic mitral repair in a lower volume center with extensive minimally invasive mitral repair experience.

The literature for robotic mitral repair is dominated by a small number of large volume institutions, and intermediate-term outcomes out to 5 years are rare. Whether and under what circumstances a lower volume institution could obtain durable outcomes is not known. A retrospective review was performed on all 133 patients undergoing robotically assisted mitral repair from 2011 to 2019 at a single institution. Mean volume of robotic mitral repair was 16 ± 7 cases per year, while mean institutional total volume of mitral repair was 116 ± 16 cases per year. Mean age was 58 ± 12 years, 77% were men, and mitral etiology was prolapse in 90%. Comorbidity was infrequent with atrial fibrillation in 20% and moderate tricuspid regurgitation in 14%. Central aortic cannulation was used in 97% with concurrent tricuspid operation in 5% and concurrent maze in 14%. Median clamp time, pump time, and length of stay were 146 min, 265 min, and 5 days, respectively, but none improved with experience. There were no deaths or stroke. At 5 years, the cumulative incidence of moderate mitral regurgitation was 18 ± 6% (prolapse patients 11 ± 5%), severe regurgitation 4 ± 3%, and mitral replacement 9 ± 5% (prolapse patients 5 ± 3%). 5-year survival was 96 ± 3%. At centers with significant mitral repair volume, a volume of 16 robotic mitral cases/year can yield good clinical outcomes durable out to 5 years. A case volume of 16 cases per year was not sufficient to improve pump time or length of stay over time.

Syncope and undifferentiated shock.

Ventricular free wall rupture is a rare post myocardial complication with a high associated mortality. In this article we discuss the case of an elderly patient who presented to our emergency department in shock after an episode of syncope. Using Point Of Care Ultrasound (POCUS), identification of cardiac tamponade and pericardial thrombus was possible, signs indicating a diagnosis of free wall rupture. Early initiation of transfer proceedings to a tertiary cardio-thoracic unit was therefore possible, resulting in a positive patient outcome.

Heart Failure Association of the European Society of Cardiology position paper on the management of left ventricular assist device-supported patients for the non-left ventricular assist device specialist healthcare provider: Part 2: at the emergency department.

The improvement in left ventricular assist device (LVAD) technology and scarcity of donor hearts have increased dramatically the population of the LVAD-supported patients and the probability of those patients to present to the emergency department with expected and non-expected device-related and patient-device interaction complications. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to suffer from other co-morbidities common in the older population. In this second part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the LVAD-supported patient presenting to the emergency department with bleeding, neurological event, pump thrombosis, chest pain, syncope, and other events are presented. The very challenging issue of declaring death in an LVAD-supported patient, as the circulation is artificially preserved by the device despite no other signs of life, is also discussed in detail.

HFA of the ESC Position paper on the management of LVAD supported patients for the non LVAD specialist healthcare provider Part 1: Introduction and at the non-hospital settings in the community.

The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of the LVAD-supported patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD-supported patients. The expected and non-expected device-related and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of the LVAD implanting centres. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to experience comorbidities common in the older population. The probability of an LVAD-supported patient presenting with medical emergency to a local emergency department, internal, or surgical ward of a non-LVAD implanting centre is increasing. The purpose of this trilogy is to supply the immediate tools needed by the non-LVAD specialized physician: ambulance clinicians, emergency ward physicians, general cardiologists, internists, anaesthesiologists, and surgeons, to comply with the medical needs of this fast-growing population of LVAD-supported patients. The different issues discussed will follow the patient's pathway from the ambulance to the emergency department and from the emergency department to the internal or surgical wards and eventually to the discharge home from the hospital back to the general practitioner. In this first part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, after the introduction on the assist devices technology in general, definitions and structured approach to the assessment of the LVAD-supported patient in the ambulance and emergency department is presented including cardiopulmonary resuscitation for LVAD-supported patients.

Guidance on the management of left ventricular assist device (LVAD) supported patients for the non-LVAD specialist healthcare provider: executive summary.

The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD supported patients. Device-related, and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of LVAD implanting centres. The probability of an LVAD supported patient presenting with medical emergency to a local ambulance team, emergency department medical team and internal or surgical wards in a non-LVAD implanting centre is increasing. The purpose of this paper is to supply the immediate tools needed by the non-LVAD specialized physician - ambulance clinicians, emergency ward physicians, general cardiologists, and internists - to comply with the medical needs of this fast-growing population of LVAD supported patients. The different issues discussed will follow the patient's pathway from the ambulance to the emergency department, and from the emergency department to the internal or surgical wards and eventually back to the general practitioner.

Immunogenicity of the BNT162b2 mRNA vaccine in heart transplant recipients - a prospective cohort study.

AIMS: To assess the short-term immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in a population of heart transplant (HTx) recipients. A prospective single-centre cohort study of HTx recipients who received a two-dose SARS-CoV-2 mRNA vaccine (BNT162b2, Pfizer-BioNTech). METHODS AND RESULTS: Whole blood for anti-spike IgG (S-IgG) antibodies was drawn at days 21-26 and at days 35-40 after the first vaccine dose. Geometric mean titres (GMT) ≥50 AU/mL were interpreted positive. Included were 42 HTx recipients at a median age of 61 [interquartile range (IQR) 44-69] years. Median time from HTx to the first vaccine dose was 9.1 (IQR 2.6-14) years. Only 15% of HTx recipients demonstrated the presence of positive S-IgG antibody titres in response to the first vaccine dose [GMT 90 (IQR 54-229) AU/mL]. Overall, 49% of HTx recipients induced S-IgG antibodies in response to either the first or the full two-dose vaccine schedule [GMT 426 (IQR 106-884) AU/mL]. Older age [68 (IQR 59-70) years vs. 46 (IQR 34-63) years, P = 0.034] and anti-metabolite-based immunosuppression protocols (89% vs. 44%, P = 0.011) were associated with low immunogenicity. Importantly, 36% of HTx recipients who were non-responders to the first vaccine dose became S-IgG seropositive in response to the second vaccine dose. Approximately a half of HTx recipients did not generate S-IgG antibodies following SARS-CoV-2 two-dose vaccine. CONCLUSIONS: The generally achieved protection from SARS-CoV-2 mRNA vaccination should be regarded with caution in the population of HTx recipients. The possible benefit of additive vaccine should be further studied.

Expression of the SARS-CoV-2 receptorACE2 in human heart is associated with uncontrolled diabetes, obesity, and activation of the renin angiotensin system.

BACKGROUND: Diabetic and obese patients are at higher risk of severe disease and cardiac injury in corona virus 2 (SARS-CoV-2) infections. Cellular entry of SARS-CoV-2 is mainly via the angiotensin-converting enzyme 2 (ACE2) receptor, which is highly expressed in normal hearts. There is a disagreement regarding the effect of factors such as obesity and diabetes on ACE2 expression in the human heart and whether treatment with renin-angiotensin system inhibitors or anti-diabetic medications increases ACE2 expression and subsequently the susceptibility to infection. We designed this study to elucidate factors that control ACE2 expression in human serum, human heart biopsies, and mice. METHODS: Right atrial appendage biopsies were collected from 79 patients that underwent coronary artery bypass graft (CABG) surgery. We investigated the alteration in ACE2 mRNA and protein expression in heart tissue and serum. ACE2 expression was compared with clinical risk factors: diabetes, obesity and different anti-hypertensive or anti-diabetic therapies. WT or db/db mice were infused with Angiotensin II (ATII), treated with different anti-diabetic drugs (Metformin, GLP1A and SGLT2i) were also tested. RESULTS: ACE2 gene expression was increased in diabetic hearts compared to non-diabetic hearts and was positively correlated with glycosylated hemoglobin (HbA1c), body mass index (BMI), and activation of the renin angiotensin system (RAS), and negatively correlated with ejection fraction. ACE2 was not differentially expressed in patients who were on angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) prior to the operation. We found no correlation between plasma free ACE2 and cardiac tissue ACE2 expression. Transmembrane serine protease 2 (TMPRSS2), metalloprotease ADAM10 and ADAM17 that facilitate viral-ACE2 complex entry and degradation were increased in diabetic hearts. ACE2 expression in mice was increased with ATII infusion and attenuated following anti-diabetic drugs treatment. CONCLUSION: Patients with uncontrolled diabetes or obesity with RAS activation have higher ACE2 expressions therefore are at higher risk for severe infection. Since ACEi or ARBs show no effect on ACE2 expression in the heart further support their safety.