End-stage Heart Failure Research Articles

Exploring the Therapeutic Potential of Gene Therapy in Arrhythmogenic Right Ventricular Cardiomyopathy.

Right dominant arrhythmogenic cardiomyopathy, commonly known as Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), represents a formidable challenge in cardiovascular medicine, as conventional therapies are commonly ineffective in impeding disease progression and the development of end-stage heart failure. Recombinant adeno-associated virus (AAV)-mediated gene therapy presents a promising avenue for targeted therapeutic interventions, potentially revolutionising treatment approaches for ARVC patients. Encouraging results from preclinical studies have sparked optimism about the possibility of curing specific subtypes of ARVC in the near future. This narrative review delves into the dynamic landscape of genetic therapy for ARVC, elucidating its underlying mechanisms and developmental stages, and providing updates on forthcoming trials. Additionally, it examines the hurdles and complexities impeding the successful translation of ARVC genetic therapies into clinical practice. Despite notable scientific advancements, the journey towards implementing genetic therapies for ARVC patients in real-world clinical settings is still in its early phases.

Initial Clinical Experience with Implantation of a New Left Ventricular Assist Device HeartCon

Objective: Heart failure is a major health problem worldwide. We report the initial experience of a new left ventricular assist device (LVAD) Heartcon—a centrifugal pump of magnetic-fluid suspension rotor integrated with the pump and machine. From September 2020 to March 2023, HeartCon was implanted in a total of 78 cases throughout China, 27 were implanted in TEDA International Cardiovascular Hospital. Methods: The patient data collected from the medical record included patient demographics, surgical and cardiopulmonary bypass (CPB) data, doses of transfused red blood cells, mechanical ventilation time (h), intensive care unit (ICU) stay time (d), and cardiac function indices assessed by echocardiography, 6-minute walk tests, and N-terminal pro brain natriuretic peptide (NT proBNP) values. Results: All patients were in New York Heart Association (NYHA) grade IV before surgery and 21 had a dilated cardiomyopathy. All patients survived the surgery. One patient underwent heart transplantation 10 months after the implantation. Eight patients reported adverse event events. The duration of mechanical ventilation after operation was 37.8 ± 52.0 h. The incidence of hemorrhagic stroke was 7.4% and the incidence of mediastinal infection was 7.4%. At 90 day followup, 25 patients were in NYHA grade I and the other 2 patients were in grade II. Conclusion: We conclude that HeartCon implantation is a safe and useful LVAD for treatment of end-stage heart failure. It provides a shorter duration of mechanical ventilation time, and a lower incidence of hemorrhagic stroke and mediastinal infection.

Growth differentiation factor-15 and routine laboratory parameters are associated with one-year mortality in patients with end-stage heart failure undergoing heart transplantation evaluation.

Growth differentiation factor-15 (GDF-15) is a hormone that regulates inflammatory responses, tissue repair, and cardiac remodeling, the three key processes underlying the development and progression of heart failure (HF). Furthermore, GDF-15 integrates information from cardiac and extracardiac disease pathways that are linked to multiorgan dysfunction in advanced stages of HF. This study aimed to determine which factors are associated with one-year mortality in patients with end-stage HF, with particular emphasis on GDF-15. We prospectively analyzed 315 consecutive hospitalized patients with end-stage HF who underwent heart transplantation evaluation between 2018 and 2022. The endpoint was all-cause mortality during one-year follow-up. We measured routine laboratory parameters and the serum GDF-15 concentration using a sandwich enzyme-linked immunosorbent assay (ELISA) (SunRedBio Technology Co, Ltd, Shanghai, China). The median age of the patients was 57 (50-62) years. During follow-up, 97 patients died. Higher serum concentrations of GDF-15 (hazard ratio [HR], 1.119; 95% CI, 1.095-1.144; P <0.001), high-sensitivity C-reactive protein (HR, 1.140; 95% CI, 1.037-1.253; P = 0.006), fibrinogen (HR, 1.003; 95% CI, 1.001-1.005; P = 0.003), bilirubin (HR, 1.055; 95% CI, 1.027-1.084; P <0.001), N-terminal pro-B-type natriuretic peptide (HR, 1.342; 95% CI, 1.206-1.493; P <0.001), and gamma-glutamyl transpeptidase (HR, 1.007; 95% CI, 1.002-1.012; P = 0.003) were independently associated with one-year mortality. Higher GDF-15, high-sensitivity C-reactive protein, fibrinogen, bilirubin, gamma-glutamyl transpeptidase, and N-terminal pro-B-type natriuretic peptide concentrations were independently associated with worse survival in patients with end-stage HF.

Evolving Strategies for Extracellular Vesicles as Future Cardiac Therapeutics: From Macro- to Nano-Applications.

Cardiovascular disease represents the foremost cause of mortality and morbidity worldwide, with a steadily increasing incidence due to the growth of the ageing population. Cardiac dysfunction leading to heart failure may arise from acute myocardial infarction (MI) as well as inflammatory- and cancer-related chronic cardiomyopathy. Despite pharmacological progress, effective cardiac repair represents an unmet clinical need, with heart transplantation being the only option for end-stage heart failure. The functional profiling of the biological activity of extracellular vesicles (EVs) has recently attracted increasing interest in the field of translational research for cardiac regenerative medicine. The cardioprotective and cardioactive potential of human progenitor stem/cell-derived EVs has been reported in several preclinical studies, and EVs have been suggested as promising paracrine therapy candidates for future clinical translation. Nevertheless, some compelling aspects must be properly addressed, including optimizing delivery strategies to meet patient needs and enhancing targeting specificity to the cardiac tissue. Therefore, in this review, we will discuss the most relevant aspects of the therapeutic potential of EVs released by human progenitors for cardiovascular disease, with a specific focus on the strategies that have been recently implemented to improve myocardial targeting and administration routes.

Platelet count in heart failure patients undergoing left ventricular assist device.

Left ventricular assist device (LVAD) implantation, a therapy for end-stage heart failure, is associated with platelet (PLT) activation. This study aims to evaluate the prognostic impact of PLT count in patients with LVAD implantation. Data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry were investigated, and patients were divided into three groups according to tertiles. The dynamic change of PLT counts and its associations with long-term outcomes were analysed. The primary outcome was long-term mortality. A total of 19517 patients who received the first continuous-flow LVAD were identified from the INTERMACS registry. The PLT count underwent a dynamic change towards normalization after LVAD implantation. Compared with intermediate, both high (hazard ratio [HR], 1.09, 95% confidence interval [CI]: 1.01 to 1.17, P=0.033) and low (HR, 1.18, 95% CI: 1.10 to 1.27, P<0.001) pre-implant PLT counts were associated with an increased risk of 2year mortality. Compared with intermediate, a high post-implant PLT count was associated with an increased risk of 4year mortality (HR, 1.38, 95% CI: 1.26 to 1.52, P<0.001). Besides, both pre- and post-implant PLT counts exhibit a U-shaped association with the risk of mortality. LVAD implantation could improve the PLT count towards normalization. Abnormal pre-/post-implant PLT counts were independently associated with increased risks of long-term mortality.

Prognosis Communication in Heart Failure: Experiences and Preferences of End-Stage Heart Failure Patients and Care Partners.

Patients with heart failure (HF) overestimate survival compared with model-predicted estimates, but the reasons for this discrepancy are poorly understood. We characterized how patients with end-stage HF and their care partners understand prognosis and elicited their preferences around prognosis communication. We conducted in-depth, semistructured interviews with patients with end-stage HF and their care partners between 2021 and 2022 at a tertiary care center in Michigan. Participants were asked to describe barriers they faced to understanding prognosis. All interviews were coded and analyzed using an iterative content analysis approach. Fifteen patients with end-stage HF and 15 care partners participated, including 7 dyads. The median patient age was 66.5 years (range, 31-80) and included 9 of 15 (60%) White participants and 9 of 15 (60%) were males. Care partners included 10 of 15 (67%) White participants and 6 of 15 (40%) were males. Care partners were partners (n=7, 47%), siblings (n=4, 27%), parents (n=2, 13%), and children (n=2, 13%). Most patients demonstrated a poor understanding of their prognosis. In contrast, care partners commonly identified the patient's rapidly declining trajectory. Patients and care partners described ineffective prognosis communication with clinicians, common barriers to understanding prognosis, and similar suggestions on improving prognosis communication. Barriers to understanding prognosis included (1) conversation avoidance by physicians, (2) information inconsistency across different physicians, (3) distractions during prognosis communication due to emphasis on other conditions, and (4) confusion related to the use of medical jargon. Most patients and care partners wanted discussions around prognosis to begin early in the course of the disease, repeated routinely using layperson's terms, incorporating both quality of life and survival assessments, and involving care partners. Both patients and care partners did not expect precise survival estimates. Patients with end-stage HF demonstrate a poor understanding of their prognosis compared with their care partners. Patients and care partners are open to discussing prognosis early, using direct and patient-centered language.

Outcomes of pediatric heart transplantation in children with selected genetic syndromes

ObjectiveGenetic syndromes (GSs) are often linked to congenital heart disease (CHD) and cardiomyopathy (CM). The effect of GSs on survival following pediatric heart transplant (HT) has not been well described. We aimed to compare outcomes following HT between children with a GS and those without a GS. MethodsThe United Network for Organ Sharing (UNOS) transplantation database was merged with the Pediatric Health Information System (PHIS) administrative database to identify children with GS who underwent HT between 2009 and 2019. Characteristics and outcomes were compared between children with a GS (GS group) and those without a GS (no GS group). ResultsGSs were present in 225 of 2429 HT recipients (9%). The most common GSs were DiGeorge syndrome (n = 28), muscular dystrophy (n = 27), Down syndrome (n = 26), and Turner syndrome (n = 14). The incidence of CHD was higher in the GS group compared to the no GS group (54% vs 38%; P < .1); however, patient demographics, hemodynamics, renal and hepatic dysfunction, and requirements for dialysis, mechanical ventilation, extracorporeal membrane oxygenation, and mechanical circulatory support were not different between the 2 groups. Time on the waitlist was not significantly different between the GS and no GS groups (55 days vs 53 days; P = .4). There also was no between-group difference in the incidence of post-transplantation complications, including dialysis (8% vs 5%; P = .38), stroke (3% vs 4%; P = .34), primary graft dysfunction (2% vs 2%; P = .75), need for pacemaker (1% vs 1%; P = .84) and rejection (3.4% vs 3.4%; P = .96). Survival at 10 years post-HT was 75% for the no GS group and 72% for the GS group (P = .59). The survival curves also did not differ between patients with CM and those with CHD. ConclusionsChildren with certain GSs and end-stage heart failure can be expected to have similar post-transplantation outcomes to those without a GS. Although early and late post-transplantation care is individualized to each patient, the presence of a GS should not influence the decision to list for HT.

Antithrombotic therapy for durable left ventricular assist devices: protocol for a living systematic review with indirect comparison/network meta-analysis

BackgroundLeft ventricular assist devices (LVADs) have emerged as a successful treatment option for patients with end-stage heart failure. Compared with the best medical therapy, LVADs improve survival and enhance functional...

Intra-operative Risk Factors Affecting Mortality after Heart Transplantation: A Referral Center Experience in Iran.

Heart transplantation is the preferred treatment for end-stage heart failure. This study investigated the intra-operative risk factors affecting post-transplantation mortality. This single-center retrospective cohort study examined 239 heart transplant patients over eight years, from 2011-2019, at the oldest dedicated cardiovascular center, Shahid Rajaee Hospital (Tehran, Iran). The primary evaluated clinical outcomes were rejection, readmission, and mortality one month and one year after transplantation. For data analysis, univariate logistic regression analyses were conducted. In this study, 107 patients (43.2%) were adults, and 132 patients (56.8%) were children. Notably, reoperation due to bleeding was a significant predictor of one-month mortality in both children (OR=7.47, P=0.006) and adults (OR=172.12, P<0.001). Moreover, the need for defibrillation significantly increased the risk of one-month mortality in both groups (children: OR=38.00, P<0.001; adults: OR=172.12, P<0.001). Interestingly, readmission had a protective effect against one-month mortality in both children (OR=0.02, P<0.001) and adults (OR=0.004, P<0.001). Regarding one-year mortality, the use of extracorporeal membrane oxygenation (ECMO) was associated with a higher risk in both children (OR=7.64, P=0.001) and adults (OR=12.10, P<0.001). For children, reoperation due to postoperative hemorrhage also increased the risk (OR=5.14, P=0.020), while defibrillation was a significant risk factor in both children and adults (children: OR=22.00, P<0.001; adults: OR=172.12, P<0.001). The median post-surgery survival was 22 months for children and 24 months for adults. There was no correlation between sex and poorer outcomes. Mortality at one month and one year after transplantation was associated with the following risk factors: the use of ECMO, reoperation for bleeding, defibrillation following cross-clamp removal, and Intensive Care Unit (ICU) stay. Readmission, on the other hand, had a weak protective effect.

Preoperative examination of inflammatory biomarkers in relation to the prognosis of postoperative complications after heart transplantation

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Semmelweis University Heart transplantation (HTX) is the definitive therapy for end-stage heart failure. Although complications have drastically decreased with modern immunosuppressive therapy, surgical and anesthetic techniques, significant complications such as graft failure, acute rejection or infection must still be expected. The purpose of the study is to examine cytokine pathways linked to inflammation from direct preoperative serum samples, which can serve as prognostic factors in relation to septic events and mortality in the early postoperative period. The study was conducted using the blood samples of 102 patients who underwent HTX. Blood samples were taken from the patients immediately before HTX. The amounts of a total of 32 cytokines and related proteins were determined using LEGENDplex assays. After that, we correlated the biomarker amounts determined in the serum samples with the end points we indicated. In patients undergoing HTX who developed septic events during postoperative intensive care, the preoperative MMP2 serum concentration was significantly higher compared to other patients undergoing HTX (n=23, p=0.04). Independent predictors of mortality in the intensive care unit (n=5) were preoperative MRP8/14 (AUC=0.8), NGAL (AUC=0.75), IGFBP-4 (AUC=0.73), cystatin C (AUC=0.7) and the MMP2 (AUC=0.74) serum concentrations. Patients transplanted from left ventricular mechanical circulatory support (LVAD) (n=11) were examined as a separate group, where early postoperative mortality was significantly higher (n=4, p=0.02), the independent predictor of which was the concentration of IGFBP-4 (p=0.04 , AUC=0.73). Based on our results, it can be said that the differences in the preoperative concentration of certain inflammatory biomarkers that can be measured in the serum show correlations with the postoperative septic events and mortality of patients undergoing HTX.

Modeling doxorubicin-induced cardiotoxicity with human myocardial tissue slices: insights on genetic susceptibility and cardioprotection

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): PSIDER and HARVEY (ZonMW) Introduction Cardiotoxicity poses a significant challenge in drug development, often leading to the withdrawal of approved drugs. To address this issue, there is a critical need for improved models to predict cardiac adverse effects. In line with the imperative for animal-free preclinical testing, this study aimed to develop a novel model using human myocardial tissue slices to get a deeper understanding and potential prevention of doxorubicin-Induced cardiotoxicity. Methods Human myocardial tissue slices of 300 μm thick were derived from end-stage heart failure patients explanted hearts, including those harbouring likely or pathogenic cardiovascular mutations (class 4 and 5) (N=3) and non-genetic cardiovascular etiology (N=3). Myocardial tissue slices were cultured under physiological mechanical and electrical conditions. Slices were exposed to doxorubicin (1 µM) over a 10-day culture period, and their responses were compared to DMSO-vehicle controls, by recording contractile force and Ca2+ transients. Additionally, a subset of slices was treated with a cardioprotective agent, dexrazoxane (100 µM), 1 day prior to and during doxorubicin exposure to assess potential cardioprotection. Results Doxorubicin-exposed slices with a pathogenic mutation exhibited reduced mechanical force, increased threshold potential, and impaired ability to follow pacing at higher frequencies. Additionally, aberrations in calcium handling, manifested as arrhythmia-like disconnection of muscle fibers, were notably observed in these slices. Instead, slices from patients without pathogenic mutations showed minimal cardiotoxicity when exposed to doxorubicin. Encouragingly, pretreatment with dexrazoxane demonstrated a protective effect against doxorubicin-induced cardiotoxicity in the genetically susceptible group. Our functional findings corroborated our structural data, highlighting the breakdown of sarcomere structure and cell-cell connections and increased DNA damage, particularly in patients harbouring a genetic cardiovascular mutation. Conclusion In summary, human myocardial tissue slices faithfully recapitulate doxorubicin-induced cardiotoxicity. Importantly, our data suggests the utility of employing genetic testing for known cardiovascular mutations as a valuable step before initiating doxorubicin treatment. Additionally, we demonstrate for the first time the in vitro cardioprotective potential of dexrazoxane in a human tissue model. These findings pave the way for using ex vivo myocardial tissue slices to evaluate cardiotoxicity and their value as a powerful tool for evaluating the efficacy and delivery approaches.

Toxicology of milrinone by zebrafish embryotoxicity test.

Milrinone, a phosphodiesterase III inhibitor with contractile and vasodilatory effects, is widely used in acute decompensated heart failure and medically refractory end-stage heart failure (HF). The adverse reactions of milrinone have been extensively explored clinically, but its possible toxicities and underlying molecular mechanisms in embryo development need further understanding as its clinical applications increase. Herein, we assessed the milrinone toxicity using the zebrafish embryotoxicity test (ZET), with a view of providing evidence and guidancefor gravidas medicine. We carried out ZET by exposing embryos to a milrinone culture with a series concentration gradients since 1.5 hours post fertilization (hpf) and observed and assessed mortality and hatching rates of drug-treated zebrafishes at 24, 48, 72, and 96 hpf. No significant lethal effect was found in milrinone-treated zebrafish, but hatching rate of eggs at 48 hpf was up-regulated with the increase of milrinone concentration. The impact of milrinone on embryogenesis was assessed through body length, eye area, yolk sac area, swim bladder inflation area, pericardial area and venous congestion area at 96hpf. 150 μg/mL or higher milrinone treatment showed significant effects in the indicators. Organ disorders including enlarged pericardium, liver atrophy and decreased blood vessels were observed in dysplasia individuals versus controls. TUNEL assay suggested the ability of milrinone to induce apoptosis in malformation embryos. Quantitative real-time PCR showed aberrant expressions of transcription factors associated with heartdevelopment and genes related to liver development and apoptosis regulation. Therefore, ZET is feasible for the milrinone toxicity test, and high-dose milrinone causes harm to the embryonic development of zebrafish, especially in embryonic carcinogenesis, vasculogenesis, and hepatogenesis.

Mid-term outcomes after stereotactic arrhythmia radioablation for refractory ventricular tachycardia

Abstract Introduction stereotactic arrhythmia radioablation (STAR) is used as a rescue treatment for refractory ventricular tachycardia (VT) originating from unreachable myocardial substrate following unsuccessful radiofrequency catheter ablation (RFCA). The mid-term outcomes of STAR, however, remain poorly known. Objective to report the mid-term efficacy and safety outcomes in our series of 21 patients (pts) treated by STAR over 6 years. Methods Inclusion of consecutive pts treated by STAR with a Cyberknife system between 2017 and 2023. 3D-electroanatomical maps (EAM) of the VT substrate during unsuccessful RFCA were used to delineate the planned target volumes (PTV) on a 4D CT scan. Patients were followed up at least every 6 months by echocardiography and ICD interrogation at the outpatient clinic. Results 21 pts [16 (76 %) male, age 66±8 years] with a mean LVEF of 40±15% were included. The underlying substrate was ischemic in 7 (33 %); non-ischemic dilated in 7 (33 %); inflammatory in 4 (19%); hypertrophic in 1 (5%); neoplasic in 1 (5%); and malignant mitral valve prolapse in 1 (5%). A dose of 21±2 Gray was delivered to the PTV (26 ml, IQR 18-43 ml). After a median follow-up of 39 [IQR, 14-48] months, 12 pts (57%) remained in stable condition, 1 (5%) underwent a heart transplantation, 1 (5%) a left ventricular assistance device, 1 (5%) was in an incessant slow VT and 6 (29%) pts died (3 from end stage heart failure). 15 (71%) pts presented VT recurrences [7 (33%) ATPs; 3 (14%) shocks; 4 (19%) VT storm and 1 (5%) with a well-tolerated slow VT (100 bpm) with an LVAD till transplantation, of whom 9 (43%) required redo RFCA. The median value of total ventricular arrhythmic burden (defined as any arrhythmia requiring ICD therapies) decreased significantly from 31 (IQR, 4-100) to 7 (IQR, 1-23) (p&amp;lt;0.05); for nsVT from 57 (IQR, 1.5- 1196) to 41 (IQR, 0.5-584) (p ns); or ICD shocks from 1.5 (IQR, 0-5.5) to 0 (IQR, 0-2) (p&amp;lt;0.05); for ATPs from 21 (IQR, 2.5-94) to 4 (IQR, 0.5-13) (p&amp;lt;0.05). Figure 1 shows a graphic representation of arrhythmic burden before and after STAR. Conclusion in this cohort of highly selected pts with refractory VT, STAR significantly reduced the arrhythmic burden by a factor of 4 over a 3-year follow-up. Death rate remained high (29%), mostly by terminal heart failure. Nevertheless, a high proportion of pts had VT recurrences that were successfully managed by redo RFCA.VT burden before and after STAR

Characterization of ventricular tachycardia ablation in end-stage heart failure patients with left ventricular assist device (CHANNELED-Registry)

Abstract Background Left-ventricular-assist-devices (LVAD) are an established therapy for patients with end-stage heart failure. These patients are at high risk for ventricular tachycardia (VT) and ICD-shocks due to the arrhythmogenic substrate of the underlying cardiomyopathy itself and as the LVAD cannula might be arrhythmogenic, too. Purpose Data on catheter ablation of VT in LVAD patients are scarce and current evidence predominantly consists of case reports and small single-center series. This multicenter registry seeks to systematically assess the mechanism and origin of VA in LVAD patients and to evaluate procedural parameters and outcome of VT ablation in this special subset of patients. Methods Retrospective data of LVAD patients referred for VT ablation at 11 tertiary care centers between January 2017 and August 2023 were included in this multicenter registry. VT mechanisms, procedural data, clinical follow-up, and outcome were assessed. Results We report 49 patients (88% male, age 61±8 years) undergoing 51 ablation procedures included in this ongoing registry. The underlying cardiomyopathy was ischemic in 25/49 patients (51%) and nonischemic in 24/49 patients (49%) with a mean left ventricular ejection fraction of 21%±6% before LVAD implantation. Most catheter ablations were conducted after prior antiarrhythmic drug (AAD) treatment (15/51 on amiodarone, 13/51 on prior intensification of amiodarone treatment, 18/51 on prior combination of two or more AADs). A total of 75 VTs were targeted (39/51 transseptal, 3/51 retrograde aortic, 9/51 combined approaches) and 13/49 patients required VT ablation less than 1 month after LVAD implantation. Of the targeted VTs the majority (69%) were cardiomyopathy related and only 31% of the targeted VTs were related to the LVAD cannula. In 5/51 procedures access site complications and in 1/51 procedures a pericardial effusion occurred; one patient showed a post procedural oxygen desaturation; despite immediate intubation the patient deceased from hypoxic brain injury. No LVAD related complications were observed. A follow-up was available for 35/49 patients. During a median follow-up of 277 days (IQR 78-625 days), 5/35 patients were transplanted and 13/35 died. Patients died after a median time of 124 days (IQR 34-952 days) primarily from heart failure, sepsis, or intracranial bleeding. Of the remaining 17/35 patients, 7/17 patients were arrhythmia-free at a median follow-up of 212 days (IQR 78-639 days). Conclusion Although often chosen as last resort, catheter ablation of VT in LVAD patients is feasible and can be performed safely in this critically ill subset of heart failure patients in experienced centers. Intrinsic myocardial scar seems to be the dominant substrate in these patients but LVAD cannulae contribute to a significant number of VTs. In the presence of severely reduced LV function the VT recurrence remains high despite maximal therapy and prognosis of these patients is limited.

Validation of the Castle HTx data in a real world scenario

Abstract Background Pulmonary vein isolation (PVI) is recommended in patients with symptomatic atrial fibrillation (AF) and reduced left ventricular ejection fraction (LVEF). Recently the Castle HTx (CHTx) trial showed a significant mortality reduction in end stage heart failure patients undergoing PVI in addition to optimized medical therapy (OMT) compared to OMT only. Aim Objective of this analysis is to validate results of Castle HTx study in a real world scenario. Methods All patients between September 2021 und September 2023 referred for PVI at our center with symptomatic AF und LVEF ≤35% were included in this retrospective analysis at the University Hospital Cologne. Results A total of 119 PVI in patients with LVEF≤35% were successfully performed (mean age 63.3±10.1 years, 96 patients (81%) male, 43 (36%) paroxysmal AF, 76 (64%) persistent AF) matching inclusion criteria used in CHTx. Cryo-PVI was used in 50 (42%), RF-PVI in 60 (50%) and PFA in 9 (8%) patients. Complete follow-up (FU) with a mean of 549.6±430.2 days was obtained in 108 patients, comparable to CHtx (540 days). During FU 11 patients (10%) died from any cause (CHTx 8 patients (8%)), 2 patients (2%) received a left ventricular assist device (CHTx 1 patient (1%)) and no patient had urgent heart transplantation (CHTx 1 patient (1%)). For 30 patients (28%) recurrence of AF was detected and 72% remained in sinus rhythm. In 6 patients (5%) post-procedural complications occurred: 5 inguinal hematoma, 1 decompensation. During FU LVEF was statistically significantly improved (EF initial 26.9±6.5%, EF FU (n=80) 37.1±12.8%, p&amp;lt;0.001) (CHTx EF initial 29.0±6.4%, EF FU (n=92) 37.2±9.1%). Conclusion The findings of the Castle HTx patients have been validated in a real-world setting. PVI for rhythm control in end stage heart failure patients is safe and highly effective. Our patient cohort, matched to the Castle HTx ablation group, showed freedom from AF rate of 72% after mean FU time of 550 days. Furthermore, LVEF was improved significantly in our cohort echoing the results from CHTx.

Pulmonary vein isolation combined with a new protocol of linear ablation to treat persistent atrial fibrillation: a prospective cohort with 1 year follow-up

Abstract Background The clinical value of ablation strategies beyond pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (perFA) is not clearly established and the optimal strategy to cure perFA remains a challenge due to the high recurrence rate after PVI alone (up to 50% of patients during 1-year follow-up). Purpose To determine the additional therapeutic value of a new design of linear ablation in the left atrium (LA) added to PVI in patients with perFA. Methods In this prospective study consecutive patients with perFA were included and underwent PVI combined with a predefined homogeneous protocol of linear ablation in the LA: anterolateral line from the mitral annulus to the left superior pulmonary vein around the left atrial appendage, anteroseptal line and posterior wall isolation. Patients were followed during 12 months after ablation with daily 30 s single-lead ECG obtained with mobile applications. The main endpoint was the incidence of recurrences, defined as any documented, sustained (&amp;gt;30 s) episodes of atrial arrhythmia that occurred after a 3 months blanking period. Antiarrhythmic drugs were avoided after the blanking period. Results 59 patients were included (61 [IQR 53-69] years old, 76% male sex). Acutely successful PVI was achieved in all patients and the linear ablation protocol was performed in 52 (89,7%) patients. The linea ablation protocol was not completed in 6 patients due to the following reasons: repetitive AF triggering from the same PV in 2 patients, induction and successful focal ablation of left atrial flutter in 1 patient, respiratory failure in 1 patient with severe obstructive lung disease and excessively prolonged procedure time in 2 patients. 58 patients completed the 12 months follow-up period and 1 patient was lost due to end-stage heart failure. The survival free of atrial arrhythmia recurrences was 69.1% [95%CI 55.1-79.5] (Figure). No patient had recurrences of perAF (&amp;gt;7 days continuous AF). 9 (53%) patients had at least 1 episode of self-limited paroxysmal AF. In these patients the average paroxysmal AF burden during the follow-up was 24 hours/year [IQR 9-24 hours/year]. In another 8 (47%) patients the recurrent arrhythmia was atypical left atrial flutter exclusively The incidence of procedure-related complications was 6,9%: 1 pericardial bleeding, 1 acute pulmonary edema, 1 splenic infarction and 1 stroke); no patient died during the study period. Conclusions A combined strategy of PVI plus the specific linear ablation protocol used in this study is associated with a low rate of atrial arrhythmia recurrences and total absence of persistent AF after ablation. A randomized multicenter clinical trial is ongoing to validate these results.Ablation strategy.Kaplan-Meier curve: recurrences

#2125 Endotypes of kidney injury in patients with acute decompensation of heart failure and their impact on long-term mortality

Abstract Background and Aims Renal dysfunction with and without albuminuria is common in patients with heart failure and associated with poorer outcomes. However, the prevalence and long-term influence of increased urine albumin creatinine ratio (uACR) and/or isolated decreased glomerular filtration rate (GFR &amp;lt; 60 ml/min/1,73 m2) have not been well studied in patients with acute decompensation of heart failure (ADHF). The aim was to investigate the prevalence of different variants of kidney injury and their impact on the mortality in patients with ADHF within 1 year of follow-up. Method This prospective, observational study included 140 patients who were discharged after ADHF. We excluded patients with terminal stage of chronic kidney disease, end-stage heart failure, malignancy. Patients were divided according to the kidney function (the maximum level of GFR) and albuminuria level taken at hospitalization into four groups: normal renal function (GFR&amp;gt;60 ml/min/1,73 m2, uACR&amp;lt;30 mg/gCr), isolated decreased GFR (GFR&amp;lt;60 ml/min/1,73 m2, uACR&amp;lt;30 mg/gCr), isolated albuminuria (GFR&amp;gt;60 ml/min/1,73 m2, uACR&amp;gt;30 mg/gCr), combined changes (GFR&amp;lt;60 ml/min/1,73 m2, uACR&amp;gt;30 mg/gCr). The observation period was 365 days. Results During hospitalization 25% (n = 35) patients had GFR&amp;gt;60 ml/min/1,73 m2, uACR&amp;lt;30 mg/gCr, 19.3% (n = 27) patients had isolated decreased GFR, 22.8% (n = 32) patients had isolated uACR&amp;gt;30 mg/gCr, and 32.9% (n = 46) patients had both. The baseline and admission characteristics are presented in the table (Fig. 1). 34 (24,3%) patients died during follow-up. Mortality was remarkably higher in groups with registered albuminuria during hospitalization regardless of GFR level (25% (n = 8) patients with isolated increased uACR, 39.1% (n = 18) patients with combined changes; with non-albuminuria: (11.4% (n = 4) patients with GFR&amp;gt;60 ml/min/1,73 m2, uACR&amp;lt;30 mg/gCr, 14.8% (n = 4) patients with isolated decreased GFR, p = 0.019 for trend). Kaplan-Meier plots revealed worse outcomes for these groups after adjusting for ejection fraction (EF) (Log-Rank p = 0.0057) (Fig. 2). In the multivariate Cox regression, in which age, gender, reduced EF and three categories of kidney damage were included, only combination of decreased GFR and albuminuria was an independent predictor of long-term mortality (hazard ratio: 3.71 95% confidential interval 1.59 to 8.67, p = 0.002). Conclusion Albuminuria is frequently observed in patients with ADHF and, especially with combination with decreased GFR, associated with higher mortality rate during 1 year of follow-up. Albuminuria with decreased GFR during hospitalization with ADHF was an independent risk factor for mortality during one year.

The role of ventricular assist device in the management of advanced heart failure: a literature review

The ventricular assist device has become a reliable and enduring therapy for patients with end-stage heart failure, with over 22,000 implantations to date. Initially designed as a bridge-to-transplant option but now it has become permanent cure for patients with acute heart failure. VAD has significant advancements in medical management and technology, particularly with the introduction of newer-generation devices, have greatly enhanced patient outcomes. This progress has led to an increasing use of ventricular assist devices as a destination therapy. Nonetheless, the substantial burden of adverse events remains a critical challenge in the current state of ventricular assist device therapy, despite this, its viable alternative of heart transplantation as it has solved the complications of donor heart and proved significant success among patient with acute heart failure.

Economic aspects of long-term left ventricular assist device treatment for chronic heart failure.

Technological advances and the current shortage of donor organs have contributed to an increase in the number of left ventricular assist device (LVAD) implantations in patients with end-stage heart failure. Demographic change and medical progress might raise the number of these patients, resulting in a further increase in the number of LVAD implantations. The aim of this study was to evaluate the long-term costs of LVAD therapy and identify diagnoses resulting in expensive stays. In this retrospective analysis of prospectively collected data, all patients after implantation of a second- or third-generation LVAD by 31 March 2022 were included. In addition to demographic and survival data, revenues and case mix points were determined for each patient. Of the 163 patients included, 75.5% were male. The mean age at LVAD implantation was 52±14years. The mean survival was 1458±127days. During follow-up, the total inpatient treatment time per patient was 70±87days. The average duration of outpatient treatment was 55.1%, based on the total duration of support. The average revenue per patient for the implant stay was $193192.35±$111801.29, for inpatient readmissions $52068.96±$116630.00, and for outpatient care $53195.94±$62363.53. LVAD implantation in patients with end-stage heart failure leads to improved survival but a significant increase in treatment costs. Further multi-centre studies are necessary in order to be able to assess the effects of long-term LVAD treatment on the healthcare system.

Using the brain to heal the heart: A case discussion and review of panhypopituitarism-induced chronic heart and kidney failure

In this paper, we present a detailed case study from our transplant evaluation clinic, focusing on a postpartum patient with end-stage heart and kidney failure being considered for heart transplantation. The evaluation revealed pituitary dysfunction, correlating with Sheehan syndrome, a condition arising from significant blood loss that leads to pituitary gland hypoperfusion and necrosis. This diagnosis is particularly noteworthy considering the pituitary gland's vital role in hormonal regulation, which impacts multiple organ systems. The gland's vulnerability to ischemia, especially due to its enlargement during pregnancy, is a critical factor. Our case highlights the necessity of thorough pre-transplant evaluations to identify reversible endocrine factors contributing to organ failure, emphasizing the complex interplay between endocrine health and organ transplant suitability. This study serves as an important reminder for clinicians to consider endocrine causes in transplant candidates, especially in postpartum patients.