End-stage Heart Failure Patients Research Articles

Advanced Markers for Hemodynamic Monitoring in Cardiogenic Shock and End-Stage Heart Failure: A Mini Review.

Right heart catheterization (RHC) provides critical hemodynamic insights by measuring atrial, ventricular, and pulmonary artery pressures, as well as cardiac output (CO). Although the use of RHC has decreased, its application has been linked to improved outcomes. Advanced hemodynamic markers such as cardiac power output (CPO), aortic pulsatility index (API), pulmonary artery pulsatility index (PAPi), right atrial pressure to pulmonary capillary wedge pressure ratio (RAP/PCWP) and right ventricular stroke work index (RVSWI) have been introduced to enhance risk stratification in cardiogenic shock (CS) and end-stage heart failure (HF) patients. CPO has emerged as a potent prognostic tool, with values below 0.6 Watts significantly associated with mortality. Similarly, API and PAPi have demonstrated strong predictive power for adverse outcomes, including death and the need for advanced HF therapies. RAP/PCWP ratio is shown to be a valuable a prognostic tool for RV dysfunction, mortality, and adverse outcomes. Despite mixed evidence on the prognostic utility of RVSWI, its physiologic relevance in assessing right ventricular function remains important. A novel clinical observation, involving patients with an RAP numerically greater than pulmonary artery saturation, was associated with a 71% 30-day mortality rate, underscoring the potential prognostic value of this finding. This review aims to summarize key advanced hemodynamic markers and their role in improving risk stratification and guiding treatment in CS and end-stage HF. The integration of these markers into clinical practice holds the potential to enhance personalized care and improve outcomes for patients with CS and advanced HF.

Psychiatric Disorders and Associated Factors in Left Ventricular Assist Device Implantation and Heart Transplant Candidates.

End-stage heart failure (ESHF) remains a significant challenge despite optimal treatment, with heart transplantation (HTx) being the gold standard of care. Mechanical circulatory support (MCS) devices such as left ventricular assist devices (LVADs) are increasingly used for temporary or permanent treatment. Psychiatric comorbidities are common in patients with ESHF and may affect treatment outcomes, but the relationship between sociodemographic, clinical, and psychiatric characteristics remains unclear. A medical record based, descriptive cross-sectional study was conducted on 94 ESHF patients scheduled for HTx or LVAD therapy. Sociodemographic, clinical, and psychiatric data, including psychiatric diagnoses and systemic inflammatory markers, were collected from medical records. Univariate analyses compared patients with (PD) and without psychiatric disorders (No-PD). Of the participants, 37% had active psychopathology, with major depressive disorder (MDD) and generalized anxiety disorder (GAD) being prevalent. Approximately half of those diagnosed received their first psychiatric diagnosis at the time of assessment. Sociodemographic factors did not differ significantly between the PD and No-PD groups. While no significant difference was observed in ejection fraction (%) and inflammatory markers such as C-reactive protein (CRP), lymphocyte count was higher in the PD group. Preoperative psychiatric assessment is crucial to identify psychiatric comorbidities in ESHF patients undergoing HTx or LVAD therapy. Despite limitations, this study sheds light on previously unexplored aspects, such as the relationship between ejection fraction and psychiatric comorbidities and the relationship between depressive symptoms and inflammatory markers obtained from complete blood count. Furthermore, the fact that almost half of the patients with psychiatric comorbidity were first diagnosed during the pre-treatment psychiatric assessment underlines the importance of pre-LVAD and pre-HTX psychiatric evaluation.

Health-Related Quality of Life among Patients with Ventricular Assist Devices in Saudi Arabia

Background: End-stage heart failure patients awaiting heart transplant often require Ventricular Assisted Devices (VAD) to support systemic and pulmonary circulation and to improve ventricular function, symptoms, and Health-Related Quality of Life (HRQoL). This study evaluates the health-related quality of life in patients with VAD and was conducted at the Cardio Ventricular Assisted Devices Clinic at King Faisal Specialist Hospital and Research Centre, Riyadh. Methods: This retrospective cohort study design included all eligible VAD patients who were still attending the cardio ventricular assisted devices clinic at KFSHRC, Riyadh. Each study participant was assigned a detailed questionnaire to assess and evaluate HRQoL outcomes measured in physical limitations, emotional stress, sexual activity, and social function from the date of device insertion to the time of data collection. Data were analyzed using the Statistical Package for Social Studies (SPSS 22; IBM Corp., New York, NY, USA). Results: Between February 2016 until June 2020, 26 patients were eligible for the study. The patients' support scores were moderate to high, indicating a positive effect on their HRQoL, with a mean score of 57.69 in emotional activity, a mean score of 34.07 in physical activity, and a mean score of 83.17 in social activity. The study's results show that the level of HRQoL varies among patients with VADs. Conclusion: Participating patients with VAD reported excellent health-related quality of life in all domains, with moderate to high support scores indicating a positive effect on their HRQoL. There is currently a lack of study on HRQoL in patients with VADs in Saudi Arabia. Therefore, this study may provide a baseline understanding of current challenges in the care of heart failure patients with VAD awaiting a heart transplant.

Long-term outcomes of apixaban as main anticoagulant in patients with HeartMate 3 left ventricular assist devices.

HeartMate 3 (HM3) left ventricular assist devices (LVADs) offer improved haemocompatibility-related outcomes for end-stage heart failure patients, facilitating the exploration of alternative anticoagulation therapies beyond warfarin. This study presents a long-term evaluation of thrombotic and bleeding outcomes in HM3 LVAD patients transitioned from warfarin to apixaban. We retrospectively identified HM3 LVAD patients at our single centre who transitioned from warfarin to apixaban. Baseline characteristics were described at discharge from implant hospitalization and at the last follow-up on each anticoagulation regimen. We reported survival, thrombo-embolic events (including LVAD pump thrombosis, stroke, arterial thrombo-embolic events and pump exchange) and bleeding events on both warfarin and apixaban. Eight patients were identified between May 2018 and June 2022 who transitioned from warfarin to apixaban 5mg twice daily. Patients were followed for a mean of 1233days after LVAD implantation and 789days after transition to apixaban. All patients were transitioned due to difficulty maintaining a therapeutic international normalized ratio (INR), including five patients who experienced bleeding complications on warfarin. No patients encountered LVAD pump thrombosis, stroke events, arterial thrombo-embolic event, pump exchange or death. While on warfarin, five patients had eight bleeding events: one major [requiring 2units of packed red blood cells (pRBCs)] and seven minors (five gastrointestinal bleeds, one episode of haematuria and one episode of haemoptysis). After switching to apixaban, one patient with angioectasia had a major gastrointestinal bleed requiring two pRBCs and endoscopic clipping. Apixaban demonstrated safe and favourable long-term outcomes in a cohort of HM3 LVAD patients over a mean follow-up of more than 2years. To our knowledge, our report provides the longest follow-up duration for this patient population to date. Larger prospective studies are needed before this can be adopted as the standard of care.

Implications of Preoperative C-Reactive Protein Levels in Heart Transplant Patients-A Single-Center Retrospective Study.

Background: Heart transplant is the final therapeutic option for end-stage heart failure patients. It has been used with increasing success as a surgical procedure, greatly influenced by advances in diagnostic and prognostic tools. The aim of this paper was to study potential implications of C-reactive protein (CRP) in patients who underwent heart transplants. Methods: Our cohort included 43 adult patients from the Emergency Institute for Cardiovascular Diseases and Transplant of Târgu Mureș who underwent heart transplants in our center between 2011 and 2023. Correlations between CRP levels and different characteristics of the patients were investigated, and the optimal cut-off value for CRP levels in relation to the 6-month mortality rate was determined. The central tendencies of the baseline characteristics of patients who had a CRP value lower than the cut-off and those with a value higher than it were compared using parametric or nonparametric tests. Results: Significant correlations between the preoperative CRP levels and 6-month mortality rate (r = 0.35; 95%CI: 0.05-0.60; p = 0.02), as well as previous cardiac resynchronization therapy (CRT) and preoperative CRP levels (r = -0.37; 95%CI: -0.61--0.07, p = 0.01) were highlighted. A value for CRP > 1.66 mg/dL was found to be associated with 6-month mortality (OR = 18.00; 95%CI: 1.90-170.33, p < 0.01). Moreover, the patients who received CRT before transplantation had significantly lower levels of CRP when compared to those who did not receive CRT (p = 0.01). Conclusions: Preoperative CRP levels could represent a valuable asset in the follow-up algorithm of heart transplant patients. The lower levels of CRP in patients who benefited from CRT before transplantation highlights the importance of understanding the complex mechanisms of inflammation and increasing focus on device therapy for future transplant recipients. Further prospective studies with larger cohorts are needed for validation.

Sericin improves alginate-gelatin hydrogels’ mechanical properties, porosity, durability and viability of fibroblast in cardiac spheroids

Biofabrication of cardiac patches is a challenging strategy proposed as an alternative to transplantation for end-stage heart failure patients. The optimization of the bioink used for this aim can be limited by costs, properties and biocompatibility of its building blocks. Lately, sericin has emerged within a wide range of natural proteins thanks to its bioadhesive and biocompatibility potential. In this study, we assessed for the first time the effects of adding silk sericin on alginate-gelatin hydrogels, proposed for cardiac applications. To this aim, we first biofabricated sericin-containing hydrogels with increasing protein concentrations. Thus, we characterized hydrogels&amp;rsquo; mechanical behaviour, porosity and structure through rheology, Brillouin microspectroscopy and SEM. Then, we bioprinted the formulated hydrogels and evaluated their effects on human cardiac spheroids (CSs) in vitro. Our mechanical characterisation demonstrated that adding sericin significantly enhanced the elasticity and the viscosity of alginate-gelatin hydrogels. Sericin also modified hydrogels&amp;rsquo; swelling behaviour and their pore size, increasing by 20%, 62%, and 92% in Ser1%, Ser2% and Ser3%, respectively. Although Ser1% did not exhibit significant effects on CSs, Ser2% and Ser3% enhanced cardiac cell viability for up to 14 days compared to the sericin-free hydrogel by acting on the fibroblast population. Sericin-based bioinks showed better printability and durability with +33% and +28% intact patches after 28 days of culture at 37&amp;deg;C compared to alginate-gelatin. Altogether our results validated the use of sericin as a promising component for the optimization of bioink intended for cardiac applications.

A Latent Cardiomyocyte Regeneration Potential in Human Heart Disease.

Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate of ≈0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial. We determined cardiomyocyte renewal in 52 patients with advanced heart failure, 28 of whom received left ventricular assist device support. We measured the concentration of nuclear bomb test-derived 14C in cardiomyocyte genomic DNA and performed mathematical modeling to establish cardiomyocyte renewal in heart failure with and without LVAD unloading. We show that cardiomyocyte generation is minimal in end-stage heart failure patients at rates 18 to 50× lower compared with the healthy heart. However, patients receiving left ventricle support device therapy, who showed significant functional and structural cardiac improvement, had a >6-fold increase in cardiomyocyte renewal relative to the healthy heart. Our findings reveal a substantial cardiomyocyte regeneration potential in human heart disease, which could be exploited therapeutically.

Abstract 4121624: Ambulatory Inotropic Support in Patients with Stage D Heart Failure Does Not Increase ICD Therapies

Background: Ambulatory inotropic infusions can be used as a palliative therapy (PT) or bridge to advanced therapies in end-stage heart failure (ESHF) patients, many of whom have implantable cardioverter defibrillators (ICDs). Research Questions: How often do patients receive ICD therapies after initiation of outpatient inotropic support and how often is defibrillation inactivated? Methods: We conducted a retrospective review of all patients discharged from an academic tertiary medical center with a new prescription for inotropic therapy between November 2017 and March 2023. Clinical data, Palliative Care consultation, and ICD interrogations before and after inotrope initiation were extracted from the electronic health record. Results: The cohort comprised 45 patients discharged on new inotropic support, including 22 (49%) with intent of PT and 23 (51%) as a bridge to advanced therapies (Figure). Among PT patients, 15 (68%) had an ICD in place with only 4 having ICD therapies deactivated at discharge. Only 2 additional PT patients had a documented discussion regarding ongoing ICD therapies. By 1 year, 4 (18%) PT patients were transitioned to hospice and 13 (59%) had died, with only 1 additional patient having ICD deactivation. Of 28 patients discharged on inotropic infusions with ICD therapies on (both PT and bridge patients), only 4 patients had ICD therapies turned off later and no ICD shocks were reported for the year following initiation of inotropic support. Conclusion: In a series of 45 patients initiated on inotropic support for PT or bridge to advanced therapies, the majority (77%) had an active ICD, but therapies were rarely delivered. Notably, there were very few documented discussions regarding ICD therapies in PT patients even with specialty Palliative Care consultation. In patients with ESHF initiated on inotropic support as PT, most patients chose to leave ICD therapies in place. For those patients, there was a low rate of ICD therapies delivered.

Abstract 4136813: Redox Serum Proteomics Of Left Ventricular Assist Device Unloaded Human Heart

Heart failure (HF) is a global epidemic claiming millions of lives worldwide. Unloading the heart of end-stage HF patients via left ventricular assist devices (LVADs) is used not only as a bridge to transplantation but also as a bridge to recovery in certain selected patients. To date, assessment of patients’ recovery from HF is based on clinical and symptomatic evaluation. The use of non-invasive biomarkers that monitor the remodeling/reverse remodeling associated with HF progression/recovery is still lacking. In this study we applied mass spectrometry-based quantitative redox proteomics to identify serum biomarkers to monitor both the progression of HF and its recovery after LVAD treatment. A fingerprint of reversed behavior at the protein and at the oxidized Cys peptide level has been discovered when comparing HF and LVAD patients. HDL proteins related to lipid metabolism were decreased in HF samples and increased in LVAD patients. In addition, a number of inflammatory proteins showed a decrease in LVAD samples and an increase in HF samples. In particular APOA4, C7, F2 or SAA2 discriminated between HF and LVAD patients. A pool of peptides containing specific oxidized Cys residues showed an inverse relationship in HF as opposed to LVAD samples. Oxidized Cys-containing peptides derived from Albumin, IGK and IGG1 discriminated HF from LVAD samples. Discriminatory sensitivity and specificity were enhanced by using a combination of the proteins APOA4, C7, F2 and the above-mentioned peptide derived from Albumin. Responders and non-responders could also be separated by proteins such as APOA4, and Cys-oxidized peptides, such as the ones derived from Albumin or IGK mentioned above. This is the first study to apply redox proteomics to explore the protein profile of the LVAD unloaded human heart. These data suggest that HDL plays an important role in LVAD recovery and that a specific group of peptides is associated with the recovery process; the mechanisms involved need further study. Our data could have important implications to the management of patients in the LVAD recovery program and could serve to identify new therapeutic targets.

Higher myocardial mitochondrial ketone body oxidation capacity in human heart failure

Abstract Introduction/Purpose Recent studies suggest that the ketone bodies (KB) beta-hydroxybutyrate (HBA) and acetoacetate (ACA) are relevant substrates for myocardial energy metabolism in heart failure (HF). However, the amount of KB-dependent mitochondrial respiration in HF has not yet been quantified. High-resolution respirometry (HRR) is the gold-standard method for quantifying substrate-dependent mitochondrial oxidative capacity. Therefore, we aimed to evaluate the association between myocardial KB-dependent oxidative capacity and human HF using HRR. Methods The primary endpoint of this single-center prospective cohort study was KB-dependent and overall mitochondrial oxidative capacity in permeabilized myocardium. We used two different protocols for our measurements. In the first HRR protocol, conventional respirometry substrates including fatty acids, complex I- and complex II substrates were used to quantify the maximum coupled oxidative phosphorylation capacity (OXPHOS). Leak respiration was quantified using oligomycin to calculate the respiratory control ratio (RCR, state 3/state 4o), and leak control ratio (LCR, state 4o/state u). In the second protocol which was recently established by our working group, HBA and ACA were used as respirometry substrates to quantify KB-dependent respiration down to the enzyme level. The relative contribution of the KBs was obtained by comparing HBA- and ACA-derived respiration to OXPHOS. We applied both protocols to myocardial samples from individuals with advanced HF (HF group, catheter-acquired endomyocardial biopsies from non-ischemic HF patients or samples of explanted hearts collected during orthotopic heart transplantation surgery in end-stage heart failure patients) as well as previously heart transplanted individuals without current heart failure (Control group). Results Controls and HF had similar demographic characteristics, with comparable age distribution (mean±SD, 56.3±10.3 vs. 54.2±10.7 years, p=0.36), sex (68.75% vs. 66.67% male, p=0.87), or body mass index (25.0±5.8 vs. 29.0±10.6 kg/m2, p=0.08) and differed significantly in cardiac index (3.06±0.67 vs. 1.93±0.44) and ejection fraction (55.8±10.2 vs. 26.6±9.1) (both p&amp;lt;0.0001). The HF group exhibited lower OXPHOS and respiration for all substrate combinations tested (Fig. 1A). In contrast, KB-dependent respiration did not differ between HF and controls (Fig. 1B). The relative HBA-dependent respiration (Fig. 1C) and the relative and absolute ACA-dependent respiration (Fig. 1C and D) were higher in the HF group compared to controls. Mitochondrial uncoupling (LCR) (0.47±0.29 vs. 0.44±0.09 [AU], p=0.79) and coupling efficiency (RCR) (2.75±1.38 vs. 2.11±0.39 [AU], p=0.15) were not different between the groups. Conclusion These findings suggest that mitochondria in the failing heart can utilize KBs for OXPHOS to a greater extent and further hint towards KB metabolism as a potential therapeutic target for HF.

Effects of atrial fibrillation ablation on arrhythmia burden and ventricular function in end-stage heart failure: Lessons from CASTLE-HTx.

The CASTLE-HTx trial showed the benefit of atrial fibrillation (AF) ablation compared to medical therapy in decreasing mortality, need for left ventricular assist device implantation or heart transplantation (HTx) in patients with end-stage heart failure (HF). Herein we describe the effects of catheter ablation on AF burden, arrhythmia recurrences, and ventricular function in end-stage HF. The CASTLE-HTx protocol randomized 194 patients in end-stage HF with AF to catheter ablation and medical therapy or medical therapy alone. AF burden, left ventricular ejection fraction (LVEF), and type of AF were assessed at baseline and at each follow-up visit. Overall, 97 patients received ablation; 66 patients (68%) underwent pulmonary vein isolation (PVI) and 31 patients (32%) were treated with PVI and additional ablation. Electroanatomic mapping showed the extent of left atrial low voltage (cardiomyopathy) >10% in 31 (31.9%) patients. At 12 months post-ablation, persistent AF was present in 31/89 patients (34.8%), which was significantly less frequent compared to baseline (p = 0.0001). Median AF burden reduction was 36.3 (interquartile range 13.6-63.3) percentage points at 12 months and LVEF improved from 29.2 ± 6.2% to 39.1 ± 8.3% (p < 0.001) following ablation. AF burden reduction <50% was significantly associated with LVEF improvement ≥5% at 12 months after ablation (p = 0.017). Atrial fibrillation ablation in end-stage HF leads to a substantial decrease in AF burden, a regression from persistent to paroxysmal AF and notably improved LVEF. Favourable ablation outcomes were observed in patients regardless of the presence or absence of signs indicating left atrial cardiomyopathy.

End-stage heart failure patients in ICU: the importance of advance planning and effective communication.

During the disease trajectory, patients with advanced heart failure are often hospitalised with a high probability of admission to the intensive care setting. Using a case study, this article explores the care given to a patient with decompensated heart failure in an intensive care unit (ICU). It will discuss the significance of holistic assessment and effective symptom management, in particular the research related to breathlessness management. The importance of effective communication within the ICU multidisciplinary team, including with the patient/family will be explored, as the ICU environment can often lead to communication breakdown, patients being unable to voice their wishes and over-medicalisation. The effectiveness of early involvement of the palliative care team in ICU will be examined, including the use of tools such advance care planning and a treatment escalation plan and whether use of these can enable a better patient and family experience at the end of life. The role of palliative care champions will be discussed.

Potential of plasma biomarkers for heart failure prediction, management, and prognosis: A multiomics perspective.

Heart failure (HF) remains a major global health challenge, and more effective and comprehensive plasma biomarkers are needed to effectively treat HF patients. Multiomics studies have shown that DNA fragments, noncoding RNAs, proteins, and metabolites may be potential plasma biomarkers for HF. However, comprehensive reviews that focus on research on plasma biomarkers for HF from an omics perspective are lacking. This review summarizes the applications of various omics approaches in the exploration of biomarkers related to the risk assessment, diagnosis, subtype classification, medical management, and prognosis prediction of HF. Moreover, as heart transplantation and left ventricular assistant device (LVAD) implantation are terminal therapies for end-stage HF patients, this review also discusses the role of cell-free DNA as a biomarker for cardiac transplant rejection and omics studies of plasma biomarkers in patients who respond to LVAD therapy. Our findings suggest that future omics research on HF biomarkers should employ integrated multiomics methods and expand the sample size to increase the robustness of the results and that the identified biomarkers should be further validated in large cohorts.

Safety and efficacy of oxycodone for refractory dyspnea in end-stage heart failure patients with chronic kidney disease: a case series of eight patients

BackgroundMorphine is effective in palliative care for patients with end-stage heart failure; however, its use is avoided in patients with impaired renal function because it tends to induce adverse effects. Although oxycodone has been reported to be a useful alternative, the evidence is insufficient. Therefore, we investigated the safety and efficacy of oxycodone in eight patients with end-stage heart failure complicated by chronic kidney disease. MethodsThis single-center retrospective study reviewed patients with end-stage heart failure who were referred to the heart failure multidisciplinary team at our institution and administered oxycodone for refractory dyspnea during hospitalization between January 2011 and December 2018. We examined the details of oxycodone usage, vital signs, and the Modified Borg Scale (MBS), which quantifies the symptoms of dyspnea and adverse events.ResultsOxycodone was administered for refractory dyspnea in eight patients with end-stage heart failure [mean age: 81 years, men: 4, New York Heart Association functional class IV: 8, median left ventricular ejection fraction: < 40% (n = 6) and ≥ 50% (n = 2)]. Renal function was reduced in all patients; the estimated glomerular filtration rate (eGFR) in seven patients was < 30 mL/min/1.73 m2. The median initial intravenous dose of oxycodone was 7.05 mg/day (range: 5–10 mg/day), and the average duration of administration was 15.8 days. Significant decreases in MBS (before: median 9, range 7–10 vs. after: median 2.5, range 1–8; p < 0.01) were observed at a median of 2.0 days (range: 2 h to 7 days) after beginning oxycodone administration. Systolic blood pressure, heart rate, and respiratory rate were not significantly altered after treatment. Adverse events, including constipation, nausea, and tremors, were observed in three patients. However, no lethal adverse events related to oxycodone treatment occurred during treatment.ConclusionsThis study revealed the clinical practice of oxycodone treatment and suggested that it is an alternative therapy as a viable palliative for refractory dyspnea in patients with end-stage heart failure who should avoid the use of morphine.

Genetic Testing Practices and Pathological Assessments in End Stage Heart Failure Patients Undergoing Heart Transplantation and Left Ventricular Assist Device

BackgroundGenetic cardiomyopathies (CM) are increasingly recognized as causes of end-stage heart failure (ESHF). Identification of a genetic etiology in ESHF has important prognostic and family implications. However, genetic testing practices are understudied in ESHF patients. MethodsThis single-center, retrospective study included consecutive ESHF patients who underwent heart transplantation (HT) or left ventricular assist device (LVAD) from 2018 to 2023. Data, including genetic testing and pathology reports, were collected from the electronic medical record. Analyses of demographic and clinical characteristics were stratified by genetic testing completion and presence of clinically actionable variant. Logistic regression was performed to evaluate for associations between histology findings and genetic variants. ResultsA total of 529 adult patients (mean age 57 years) were included in the study and were predominantly male (79%, 422/529) and non-white (61%, 322/529). Genetic testing was performed in 54% (196/360) of patients with either non-ischemic or mixed CM. A clinically actionable result was identified in 36% (70/196) of patients, of which, only 43% (30/70) had a genetic counselor referral. The most common genetic variants were TTN (32%, 24/75), MYBPC3 (13%, 10/75), and TTR (11%, 8/75). Clinically actionable variants were identified in patients with known heart failure precipitators, such as alcohol use. In multivariable analysis, presence of interstitial fibrosis, specifically diffuse, on pathology was significantly associated with a clinically actionable variant (aOR 2.29, 95% CI [1.08-4.86], p = 0.03). ConclusionESHF patients with non-ischemic or mixed CM undergoing advanced therapies had a low uptake of genetic services, including testing and counselors, despite a high burden of genetic disease. Pathology findings, such as interstitial fibrosis, may provide insight into genetic etiology. The underutilization of services suggests a need for implementation strategies to improve uptake.

Fibrin clot permeability (Ks) in patients on left ventricular assist device

Patients on left ventricular assist devices (LVAD) are prone to excessive hemostasis disturbances due to permanent contact of artificial pump surfaces with blood components. We aimed to investigate if fibrin clot permeability is altered in patients on long-term continuous-flow LVAD therapy and if the clot permeability is associated with clinical characteristics and adverse events. We investigated 85 end-stage heart failure patients (90.6% men, age 48.6–63.8 years) scheduled for continuous flow long-term LVAD support according to current clinical indications. The patients were assessed periodically: prior to LVAD implantation (T1), 3–6 months (T2) after LVAD implantation, 6–12 months after (T3) and then every 6 months. We tested the first three blood samples (T1-T3) and the last available blood sample (T4), but no longer than 5 years after LVAD implantation. We assessed hemostasis parameters (Activated Partial Thromboplastin Time (APTT) Prothrombin Time, Activated Partial Thromboplastin Time, Fibrinogen, d-dimer, Antithrombin, Thrombin Time, Factor VIII, and von Willebrand Factor, aspirin-induced platelet inhibition, adenosine-diphosphate test) changes during the study period. Fibrin Clot Permeability was evaluated using a pressure system and Permeability Coefficient (Ks) was calculated. We observed a decrease in fibrin clot permeability (Ks) between T1, T2, T3 and T4 time periods; P < 0.01 for each comparison. Fibrin clot permeability was negatively correlated with fibrinogen concentration: r = − 0.51, P < 0.001, factor VIII activity r = − 0.42, P < 0.001. There was no association of Ks with age, Left Ventricular Ejection Fraction (LVEF) and medications P > 0.001, however cumulative measurements in patients on aspirin showed shortening of Ks in this group P = 0.0123. Major adverse cardiac and cerebrovascular events (MACCE) occurred in 36.5% patients, bleeding events in 25.9%, Net Adverse Clinical Events (NACE) in 62.4%; 31.7% patients died, and 17.6% underwent transplantation. The transplantation was considered as the endpoint. Discrepancies in Ks were observed between patients with MACCE, bleeding, and NACE, and patients without adverse events. Ks showed a constant trend towards normalization (P < 0.01) only in patients without adverse events. Patients with advanced heart failure have disturbed clot structure. A trend towards normalization of the Ks values is associated with fewer thromboembolic and bleeding complications in this group of patients.

Non-alcoholic fatty liver disease and heart failure: A comprehensive bioinformatics and Mendelian randomization analysis.

Heart failure (HF) and non-alcoholic fatty liver disease (NAFLD) are significant global health issues with a complex interrelationship. This study investigates their shared biomarkers and causal relationships using bioinformatics and Mendelian randomization (MR) approaches. We analysed NAFLD and HF datasets from the Gene Expression Omnibus (GEO). The GSE126848 dataset included 57 liver biopsy samples [14 healthy individuals, 12 obese subjects, 15 NAFL patients and 16 non-alcoholic steatohepatitis (NASH) patients]. The GSE24807 dataset comprised 12 NASH samples and 5 healthy controls. The GSE57338 dataset included 313 cardiac muscle samples [177 HF patients (95 ischaemic heart disease patients and 82 idiopathic dilated cardiomyopathy patients) and 136 healthy controls]. The GSE84796 dataset consisted of 10 end-stage HF patients and 7 healthy hearts procured from organ donors. We identified differentially expressed genes (DEGs) and constructed a protein-protein interaction (PPI) network. Functional pathways were elucidated through enrichment analyses using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneMANIA annotation. Single nucleotide polymorphism (SNP) data for HF and NAFLD were sourced from genome-wide association studies (GWAS). The HF dataset included 486160 samples (14262 experimental and 471898 control), and the NAFLD dataset comprised 377988 samples (4761 experimental and 373227 control). MR analysis investigates the causal interrelations. Our analysis revealed 4032 DEGs from GSE126848 and 286 DEGs from GSE57338. The top 10 hub genes (CD163, VSIG4, CXCL10, FCER1G, FPR1, C1QB, CCR1, C1orf162, MRC1 and CD38) were significantly enriched in immune response, calcium ion concentration regulation and positive regulation of monocyte chemotaxis. CIBERSORT analysis indicated associations between these hub genes and natural killer (NK) cells and macrophages. Transcription factor (TF) target prediction for CD38, CXCL10 and CCR1 highlighted related TFs. A two-sample MR analysis confirmed a bidirectional causal relationship between NAFLD and HF. The main method [inverse variance weighted (IVW)] demonstrated a significant positive causal relationship between NAFLD and HF [P=0.037; odds ratio (OR)=1.024; 95% confidence interval (CI): 1.001 to 1.048]. Similarly, HF was associated with an increase in the risk of NAFLD (P<0.001; OR=1.117; 95% CI: 1.053 to 1.185). Our findings reveal novel molecular signatures common to NAFLD and HF and confirm their bidirectional causality, highlighting the potential for targeted therapeutic interventions and prompting further investigation into their intricate relationship.

Evaluation of thrombosis and bleeding events in the children with left ventricular assist device (L-VAD)

This study aimed to evaluate thrombosis and bleeding events in the children implanted with two types of ventricular assist devices (VAD). A total of 26 paediatric end-stage heart failure patients with the mean age of 11.32 ± 4.17 years, 15 were boys, implanted with a VAD, either the Berlin Heart EXCOR (BHE group; n = 9) or the HeartWare (HW group, n = 17), were included in this retrospective study. Follow up data on bleeding events, thrombosis events, bridge-to-transplantation rates and survival outcome were recorded. Overall, 16(33.3%) bleeding events and 32(66.7%) thrombosis events occurred, while 14(53.8%) patients had at least one thrombotic event and 8(30.8%) patients had at least one bleeding event. BHE and HW groups were similar in terms of number of patients with at least one thrombotic (33.3% vs. 64.7%, p = .218) or bleeding (22.2% vs.35.3%, p = .399) event. Mortality occurred in 9(34.6%) patients and 13(50.0%) patients achieved bridge-to-transplantation, similarly in BHE and HW groups (mortality: 44.4% vs. 29.4%, p = .667 and transplantation: 77.8% vs. 35.3%, p = .097). In conclusion, our findings revealed that VAD application in children with heart failure enables successful heart transplantation achievement with an acceptable risk of bleeding/thromboembolic events in most of cases. More advanced VAD technologies and more successful management for haematologic complications are necessary to improve the transplantation rates in children.

Unmet need for heart transplantation in Africa.

Heart transplantation is a critical treatment option for end-stage heart failure patients, offering a lifeline for those with severe cardiac conditions. However, in Africa, the unmet need for heart transplantation is a significant issue that poses challenges to the healthcare system and patient outcomes. Africa faces multiple barriers to heart transplantation, including limited infrastructure, a shortage of skilled healthcare professionals, a lack of funding, and inadequate organ donation systems. These challenges result in a considerable gap between the demand for heart transplants and the available resources to meet this need. As a result, many patients in Africa do not have access to life-saving heart transplantation procedures, leading to high mortality rates among those awaiting transplants. Addressing the unmet need for heart transplantation in Africa requires a multifaceted approach. The authors recommend that Africa as a continent build up a heart transplantation workforce involving a multidisciplinary team that consists of transplant surgeons, transplant physicians, nurses, anesthetists, pharmacists, etc. Heart transplant education and training programs should be well-constructed to ensure the delivery of safe and effective transplantation services. International collaborations have proven to be effective and should be encouraged between African institutions and transplant centers worldwide to facilitate knowledge transfer. Foreign and local organizations should promote public awareness about organ donation to address the myths about heart transplantation and promote heart donation. With these, African countries can improve access to heart transplantation, enhance patient outcomes, save lives in the region, and ultimately reduce the mortality rate in Africa.

Undetected Neuromuscular Disease in Patients after Heart Transplantation.

(1) Heart transplantation (HTX) improves the overall survival and functional status of end-stage heart failure patients with cardiomyopathies (CMPs). The majority of CMPs have genetic causes, and the overlap between CMPs and inherited myopathies is well documented. However, the long-term outcome in skeletal muscle function and possibility of an undiagnosed underlying genetic cause of both a cardiac and skeletal pathology remain unknown. (2) Thirty-nine patients were assessed using open and standardized interviews on muscle function, a quality-of-life (EuroQol EQ-5D-3L) questionnaire, and a physical examination (Medical Research Council Muscle scale). Whole-exome sequencing was completed in three stages for those with skeletal muscle weakness. (3) Seven patients (17.9%) reported new-onset muscle weakness and motor limitations. Objective muscle weakness in the upper and lower extremities was seen in four patients. In three of them, exome sequencing revealed pathogenic/likely pathogenic variants in the genes encoding nexilin, myosin heavy chain, titin, and SPG7. (4) Our findings support a positive long-term outcome of skeletal muscle function in HTX patients. However, 10% of patients showed clinical signs of myopathy due to a possible genetic cause. The integration of genetic testing and standardized neurological assessment of motor function during the peri-HTX period should be considered.