Advanced Therapy Research Articles

Neuroimaging Insights into Autism Spectrum Disorder: Structural and Functional Brain

Autism Spectrum Disorder (ASD) is a condition that affects social communication, behavior, and interests. This review analyzes recent brain imaging studies to understand the biological basis of ASD. Studies using structural magnetic resonance imaging (sMRI) show that people with ASD often have less gray matter in key brain areas like the amygdala and superior temporal sulcus. There are also concerns with white matter connections in the brain. Functional magnetic resonance imaging (fMRI)studies show reduced connectivity within critical brain networks and irregular activation patterns when processing social information. Intervention studies suggest that targeted training can improve brain function related to social skills. Postmortem research reveals cellular and synaptic changes, such as fewer Purkinje cells and altered neuron organization. These findings highlight the importance of studying the social brain network in ASD and suggest the need for more long-term, comprehensive studies. This review is intended to contribute to the development of advanced diagnostic tools and therapies that will ultimately enhance the quality of life for individuals with ASD.

Risk Stratification and Management of Intermediate- and High-Risk Pulmonary Embolism.

Acute pulmonary embolism (PE) is a leading cause of mortality. Not only is PE associated with short-term mortality, but up to ~20% of patients might suffer from long-term consequences such as post-PE syndrome and chronic thromboembolic pulmonary hypertension. Current risk stratification tools poorly predict those who are at risk for short-term deterioration and those who develop long-term consequences. Traditionally, systemic thrombolysis has been considered the first-line therapy for patients with high-risk PE without contraindications; however, it comes with the risk of major bleeding (notably intracranial hemorrhage). The use of catheter-directed interventions (embolectomy or thrombolysis) has been increasing owing to their low bleeding risk; however, randomized trial data supporting their efficacy in improving clinical outcomes are limited. In this review, we highlight the evidence supporting the available advanced therapies for high- and intermediate-risk PE and summarize the ongoing trials which are evaluating these therapies.

Repurposing Antiviral Drugs as Potential Anti-EGFR Agents in NSCLC: A Structure-Based Screening and Molecular Dynamics Analysis.

One of the problems resulting from recurrent hyperactivated or mutant epidermal growth factor receptors (EGFR) in non-small cell lung cancer (NSCLC) is therapeutic resistance. Consequently, this leads to increased expressionof oncogenicproteins and reduces the efficacy of EGFR tyrosine kinase inhibitors (TKIs). This study assessed antiviral drug efficacy as potential anti-EGFR agentsfor NSCLC. We used structure-based virtual screening to evaluate 66 antiviral drugs thoroughly. The top 6 antiviral drugs exhibiting impressive binding energies (i.e. surpassing a threshold of -8.5 kcalmol-1) were identified. Subsequent bioactivity analysis and ADMET profiling were performed to select the most promising candidates, followed by a molecular dynamic simulation. Among the selected antiviral regimens, dolutegravir demonstrated the highest docking score (-9.8 kcalmol-1), followed by rilpivirine and ensitrelvir, surpassing other candidates and our reference EGFR TKI. Further molecular dynamics simulations revealed promising dynamic interactions of dolutegravir, ensitrelvir, and rilpivirine with the EGFR target as compared with afatinib. Our findings highlight the repositioning potential of antiviral drugs for anti-EGFR drug discovery, supported by their robust docking scores, ADMET profiles, dynamic interactions, and binding free energies. The results open up new avenues for advanced NSCLC therapy. Further in vitro investigations are warranted to evaluate their efficacy and safety.

The effectiveness of vedolizumab in advanced therapy-experienced ulcerative colitis patients: Real world data from the Inflammatory Bowel Disease of the Middle East (IBD-ME) Registry group.

Vedolizumab is an approved ulcerative colitis (UC) treatment. Multiple large randomized clinical trials have demonstrated the drug's efficacy and safety. However, real-world data from Middle Eastern countries are spare. The study aims to evaluate the clinical efficacy of vedolizumab (VDZ) therapy in advanced therapy experienced UC patients. A retrospective electronic chart review of a cohort study of 153 moderately to severely active UC patients who failed or were intolerant to TNF antagonists and received vedolizumab from two large tertiary care centers was performed. Rates of clinical response and remission were retrospectively evaluated at 3,6, and 12 months post VDZ therapy using Patient Simple Clinical Colitis Activity Index (P-SCCAI); clinical response was defined as a decrease in P-SCCAI ≥3, and clinical remission was defined as a P-SCCAI score of ≤3 points. Logistic regression analysis was used to identify predictors of response to vedolizumab. A total of 153 UC patients had sufficient data for analysis. Clinical remission rates were 61.9% for patients on vedolizumab every 8 weeks and 89.3% for those receiving every 4 (Q4) weeks dosing. A significant reduction in CRP and improvement of albumin post vedolizumab treatment were observed, and corticosteroids were stopped in most patients. In a multiple logistic regression analysis, several factors were found to influence the clinical effectiveness of VDZ in inducing remission. Female gender was associated with a higher likelihood of remission [OR =3.09, 95% CI = (1.05-9.13), P = 0.04]. Conversely, a greater number of biologics used prior to VDZ treatment was associated with a lower likelihood of remission [OR =0.418, 95% CI = (0.203-0.859), P = 0.017]. Patients with extensive disease (E3) had an increased likelihood of remission [OR =3.81, 95% CI = (1.32-10.97), P = 0.0129]. Additionally, a VDZ dosing frequency of Q4 weeks was associated with a significantly higher likelihood of remission [OR =6.08, 95% CI = (1.73-21.39), P = 0.0049]. No significant safety signals were reported. In this current real-world study, vedolizumab effectively achieved clinical response and remission in most advanced therapy experienced UC patients treated for up to 12 months. Future studies with larger sample sizes and more robust study designs should be conducted to further validate the results of this study.

Real-World Comparison of Effectiveness, Treatment Persistence, and Safety of First-Line Advanced Therapies at 1 Year for Ulcerative Proctitis

Lay Summary In this retrospective cohort study, vedolizumab was associated with higher odds of steroid-free clinical remission at 1 year compared to anti-TNF agents for bio-naïve patients with ulcerative proctitis.

Contemporary clinical role of echocardiography in patients with advanced heart failure.

Echocardiography represents an essential tool for imagers and clinical cardiologists in the management of patients with heart failure. Advanced heart failure (AdHF) is a more severe and, typically, later stage of HF that exposes patients to a high risk of adverse outcomes, with a 1-year mortality rate of around 50%. Currently, several therapies are available to improve the outcomes of these patients, reduce their mortality rate, and, possibly, delay the need for advanced therapies such as heart transplant and long-term mechanical circulatory support. When accurately performed and interpreted, echocardiography provides crucial information to properly tailor medical and device therapy of patients with AdHF and to identify those at even higher risk. In this review, we present the state of the art of echocardiography applications in the clinical management of patients with AdHF. We will discuss the role of echocardiography chronologically, beginning with the prediction of AdHF, proceeding through diagnosis, and detailing how echocardiography informs clinical decision-making, before concluding with indications for advanced therapies.

16S rRNA based metagenomic analysis unveils unique oral microbial signatures in oral squamous cell carcinoma cases from Coastal Karnataka, India.

Oral Squamous cell carcinoma (OSCC) is the 14th most frequent cancer with 300,000 new cases and 100,000 deaths reported annually. Even with advanced therapy, the treatment outcomes are poor at advanced stages of the disease. The diagnosis of early OSCC is of paramount clinical value given the high mortality rate associated with the late stages of the disease. Recently, the role of microbiome inthedisease manifestation, including oral cancer, has garnered considerable attention. But, to establish the role of bacteria in oral cancer, it is important to determine the differences in the colonization patternin non-tumour and tumour tissues. In this study, 16S rRNA based metagenomic analyses of 13tumorous and contralateral anatomically matched normal tissue biopsies, obtained from patients with advanced stage of OSCC were evaluated to understand the correlation between OSCC and oral microbiome. In this study we identified Fusobacterium, Prevotella, Capnocytophaga, Leptotrichia, Peptostreptococcus, Parvimonas and Bacteroidetes as the most significantly enriched taxa in OSCC lesions compared to the non-cancerous tissues. Further, PICRUSt2 analysis unveiled enhanced expression of metabolic pathways associated with L-lysine fermentation, pyruvate fermentation, and isoleucine biosynthesis in those microbes associated with OSCC tissues. These findings provide valuable insights into the distinctive microbial signatures associated with OSCC, offering potential biomarkers and metabolic pathways underlying OSCC pathogenesis. While our focus has primarily centred onmicrobial signatures, it is essential to recognize the pivotal role of host factors such as immune responses, genetic predisposition, and the oral microenvironment in shaping OSCC development and microbiome composition.

New perspectives on the role of platelet factors in enhancing wound regeneration

Aim. To analyze the use of biological factors in the stimulation of the wound healing process. In the course of the study, we analysed relevant domestic and foreign literature sources on the given topic.Methods. The literature was reviewed using the key query ‘the role of biological factors in wound healing stimulation’ through the eLIBRARY and PubMed databases.Results. Currently, the range of therapeutic approaches is broad and diverse, incorporating both traditional and experimental methods such as advanced dressings, tissue matrices, growth factors (GFs), cell therapy, and nanotechnology. The wound healing process is regulated by a complex interplay of intercellular, intracellular, and extracellular signalling mechanisms across various phases of healing.Conclusion. The application of platelet-based therapies in different medical fields has shown promising outcomes in certain conditions, such as acute and chronic injuries of bone and cartilage. However, platelet-based preparations have yet to gain widespread clinical use. Several studies have demonstrated the involvement of platelets and related products, such as platelet microparticles (PMPs) and exosomes, in multiple phases of wound healing. The presence of a substantial number of biologically active molecules within platelet granules—exhibiting anti-inflammatory, angiogenic, proliferative, and other properties—renders platelets particularly attractive for use in regenerative medicine, including the stimulation of wound healin

Are Small Molecules Effective in Treating Inflammatory Pouch Disorders Following Ileal Pouch-Anal Anastomosis for Ulcerative Colitis? Here Is Where We Stand.

Ulcerative colitis (UC) management encompasses conventional and advanced treatments, including biological therapy and small molecules. Surgery, particularly in the form of ileal pouch-anal anastomosis (IPAA), is indicated in cases of refractory/severe disease. IPAA can lead to acute complications (e.g., acute pouchitis) as well as late complications, including chronic inflammatory disorders of the pouch. Chronic pouchitis, including the antibiotic-dependent (CADP) and antibiotic-refractory (CARP) forms, represents a significant and current therapeutic challenge due to the substantial need for evidence regarding viable treatment options. Biological therapies have shown promising results, with infliximab, adalimumab, ustekinumab, and vedolizumab demonstrating some efficacy in chronic pouchitis; however, robust randomized clinical trials are only available for vedolizumab. This narrative review focuses on the evidence concerning small molecules in chronic pouchitis, specifically Janus kinase (JAK) inhibitors and sphingosine-1-phosphate receptor (S1P-R) modulators. According to the preliminary studies and reports, Tofacitinib shows a potential effectiveness in CARP. Upadacitinib presents variable outcomes from the case series, necessitating further evaluation. Filgotinib and ozanimod demonstrate anecdotal efficacy. This review underscores the need for high-quality studies and real-world registries to develop robust guidelines for advanced therapies in post-IPAA inflammatory disorders, supported by vigilant clinical monitoring and ongoing education from international IBD specialist societies.

Decision Aid-Led Tapering of Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis: A Qualitative Study.

To explore the experiences and perspectives of patients and rheumatologists on decision aid (DA)-led tapering of advanced therapy in rheumatoid arthritis (RA). Semistructured interviews were completed with patients and rheumatologists, embedded within a pilot study of DA-led tapering (ie, dose reduction) of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) in RA. All patients were in sustained (≥ 6 mos) remission and had chosen to reduce their therapy after a DA-led shared decision with their rheumatologist. The rheumatologists included those participating in the pilot (n = 4), and those who were not (n = 8). Reflexive thematic analysis of audiotaped and transcribed interviews identified themes in the group experiences. Patients (n = 10, 6 female) unanimously found the DA easy to understand and felt confident in shared decision making about treatment tapering and managing flares. Rheumatologists' (n = 12, 5 female) perspectives on tapering bDMARDs and tsDMARDs varied widely, from very supportive to completely opposed, and influenced their views on the DA. Rheumatologists expressed concerns about patient comprehension, destabilizing a stable situation, risks of flare, and extending appointment times. Despite their initial reservations about sending the DA to all eligible patients ahead of appointments, 3 of 4 participating rheumatologists adopted this approach during the pilot, which had the benefit of facilitating patient-led conversations. A DA-led strategy for tapering advanced therapy in RA was acceptable to patients and feasible in practice. Sending patients a DA ahead of their appointment facilitated patient-led conversations about tapering.

Transthyretin amyloidosis. Fundamentals of pathogenesis, diagnosis, treatment, prognosis

Among the 42 human amyloidoses described to date the so-called systemic transthyretin amyloidosis, which comprises hereditary forms (more than 140 variants in accordance with the number of identified mutations in the transthyretin gene) and a sporadic form without structural changes in the gene and the protein, is of particular interest. This review summarizes modern understandings of pathogenesis of transthyretin amyloidosis. The symptoms of different forms of transthyretin amyloidosis, issues of early diagnosis, differential diagnosis (including within the group of amyloidoses), advanced therapy and prognosis are considered. Special attention is given to the non-mutant form of transthyretin amyloidosis, the so-called senile amyloidosis, which significantly complicates the course of underlying pathologies in the age group older than 70 years and is still poorly diagnosed. A quite high occurrence of non-mutant form of transthyretin amyloidosis makes it to be considered as a socially significant disease.

Overactive bladder: results from patients treated by hyaluronic acid-chondroitin sulphate therapy.

Overactive bladder (OAB) is a chronic condition. This study was prompted by the need to fill the gap between medical treatment and advanced therapies allowing improvement in Quality of Life. The aim of the current study was to evaluate the association between treatment type (Ialuril®; IBSA Farmaceutici, Lodi, Italy; in combination with antimuscarinic or alone after drop-out of antimuscarinic, relative to antimuscarinic alone treatment) and functional outcomes (number of micturitions, pelvic pain, urinary incontinence, nocturia, urgency). Of all patients newly diagnosed (January 2016 - January 2022) with OAB syndrome, we retrospectively identified 150 patients. They harbored three groups of 50 patients each: group 1 (antimuscarinic drug), group 2 (antimuscarinic drug + hyaluronic acid-chondroitin sulphate [HA-CS]), group 3 (antimuscarinic dropout patients). Univariable linear and logistic regression models were fitted for number and rates of incontinence, urgency, pelvic pain, nocturia, respectively. A significant mean reduction of 1.5 micturition (P=0.02) was recorded in group 2 compared to group 1. Conversely, no statistically significant mean difference was recorded in group 3 compared to group 1. Regarding pelvic pain, both group 2 and group 3 were associated with lower rate of pelvic pain (P<0.001). Regarding urgency, a statistically significant protective OR was recorded for group 2 (OR=0.39; P=0.04), compared to group 1. The combination therapy was associated with symptom improvement in antimuscarinic naïve OAB patients. Conversely in antimuscarinic dropped-out patients only pelvic pain improved with the HS-CA. No statistically significant differences were recorded for other functional outcomes, such as incontinence and nocturia.

Evaluation and Management of Kidney Dysfunction in Advanced Heart Failure: A Scientific Statement From the American Heart Association.

Early identification of kidney dysfunction in patients with advanced heart failure is crucial for timely interventions. In addition to elevations in serum creatinine, kidney dysfunction encompasses inadequate maintenance of sodium and volume homeostasis, retention of uremic solutes, and disrupted endocrine functions. Hemodynamic derangements and maladaptive neurohormonal upregulations contribute to fluctuations in kidney indices and electrolytes that may recover with guideline-directed medical therapy. Quantifying the extent of underlying irreversible intrinsic kidney disease is crucial in predicting whether optimization of congestion and guideline-directed medical therapy can stabilize kidney function. This scientific statement focuses on clinical management of patients experiencing kidney dysfunction through the trajectory of advanced heart failure, with specific focus on (1) the conceptual framework for appropriate evaluation of kidney dysfunction within the context of clinical trajectories in advanced heart failure, including in the consideration of advanced heart failure therapies; (2) preoperative, perioperative, and postoperative approaches to evaluation and management of kidney disease for advanced surgical therapies (durable left ventricular assist device/heart transplantation) and kidney replacement therapies; and (3) the key concepts in palliative care and decision-making processes unique to individuals with concomitant advanced heart failure and kidney disease.

Achieving equitable access to incretin-based therapies in cardiovascular care

The role of incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP1RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, in the management of type 2 diabetes mellitus (T2DM) and obesity has been increasingly recognized, along with significant cardiovascular (CV) benefits. Despite the clinical efficacy of incretin-based therapies, high costs, suboptimal access, limited insurance coverage, and therapeutic inertia present substantial barriers to widespread adoption. Overcoming these obstacles is essential for the equitable initiation, access, and utilization of incretin-based therapies. Clinicians must make targeted efforts to ensure health equity in the use of these and other advanced therapies.

Short term outcomes and resource utilization in de-novo versus acute on chronic heart failure related cardiogenic shock: a nationwide analysis.

There has been growing recognition of non-ischemic etiologies of cardiogenic shock (CS). To further understand this population, we aimed to investigate differences in clinical course between acute on chronic heart failure related (CHF-CS) and de-novo CS (DN-CS). Using the Nationwide Readmission Database, we examined 92,426 CS cases. Outcomes of interest included in-hospital and 30-day outcomes and use of advanced heart failure therapies. Patients with DN-CS had higher in-hospital mortality than the CHF-CS cohort (32.6% vs. 30.4%, p < 0.001). Mechanical circulatory support (11.9% vs. 8.6%, p < 0.001) was more utilized in DN-CS. Renal replacement therapy (13.8% vs. 15.5%, p < 0.001) and right heart catheterization (16.0% vs. 21.0%, p < 0.001) were implemented more in the CHF-CS cohort. The CHF-CS cohort was also more likely to undergo LVAD implantation (0.4% vs. 3.6%, p < 0.001) and heart transplantation (0.5% vs. 2.0%, p < 0.001). Over the study period, advanced heart failure therapy utilization increased, but the proportion of patients receiving these interventions remained unchanged. Thirty days after index hospitalization, the CHF-CS cohort had more readmissions for heart failure (1.1% vs. 2.4%, p < 0.001) and all causes (14.1% vs. 21.1%, p < 0.001) with higher readmission mortality (1.1% vs. 2.3%, p < 0.001). Our findings align with existing research, demonstrating higher in-hospital mortality in the DN-CS subgroup. After the index hospitalization, however, the CHF-CS cohort performed worse with higher all-cause readmission rate and readmission mortality. The study also underscores the need for further investigation into the underutilization of certain interventions and the observed trends in the management of these CS subgroups.

Clinical Outcomes and Left Ventricular Functional Remodeling after Extracorporeal Membrane Oxygenation Assisted Percutaneous Coronary Intervention in Patients with Ischemic Cardiomyopathy: A Single-Center Retrospective Observational Study of 76 Cases.

Ischemic cardiomyopathy (ICM) is a common condition that leads to left ventricular (LV) functional remodeling and poor prognosis. Extracorporeal membrane oxygenation (ECMO) can provide temporary circulatory support and facilitate percutaneous coronary intervention (PCI) in patients with ICM and hemodynamic instability. However, the impact of ECMO-assisted PCI on LV functional remodeling and clinical outcomes in ICM patients is unclear. We retrospectively analyzed 76 patients with ICM who underwent ECMO-assisted PCI at our institution between January 2013 and December 2022. We assessed the changes in LV functional remodeling using echocardiography at baseline and 12 months after the procedure. We also evaluated the incidence of major adverse cardiac and cerebrovascular events (MACCEs) and ECMO-related complications during hospitalization and at one-year follow-up. The mean baseline left ventricular ejection fraction (LVEF) was 29.98 ± 2.65%. The rate of complete revascularization was 58%. The median duration of ECMO support was 38.99 hours. The most common ECMO-related complications were bleeding (8%) and lower extremity ischemia (5%). The one-year mortality rate was 30%. The overall freedom from MACCEs at 12 months was 59% (95% confidence interval (CI): 49-71%). LVEF increased significantly after the procedure from baseline to 6 months, yet decreased slightly at 12 months, although it was still higher than the baseline value. Wall motion score index (WMSI), end-diastolic volume index (EDVI), and end-systolic volume index (ESVI) decreased significantly from baseline to 12 months, indicating an improvement in LV function and a reduction in LV size. In a high-volume tertiary center with extensive experience in advanced heart failure therapies and a dedicated ECMO team, ECMO-assisted PCI demonstrated feasibility and safety in patients with ischemic cardiomyopathy. However, the rate of complete revascularization was modest at 58%. Despite the high-risk profile of the patients, ECMO-assisted PCI was associated with a significant improvement in LV functional remodeling and a favorable 12-month survival rate. Further prospective studies are needed to confirm these findings and to identify the optimal patient and device selection criteria for ECMO-assisted PCI.

Citrus aurantifolia-derived carbon quantum dots with red fluorescence emission for codelivery with curcumin as theranostic liposomes for lung cancer

BackgroundCarbon dots (CDs) derived from Citrus aurantifolia represent a promising platform for advanced cancer therapy and diagnostics (theranostics). These CDs are synthesized through a sustainable and cost-effective hydrothermal method, utilizing fruit juice as a green carbon source. Despite the potential, research on the synthesis of citrus-based CDs, especially regarding their red fluorescence emission, which is crucial for enhanced tissue penetration and biomedical efficacy, remains limited.ResultsIn this study, CDs were successfully synthesized from C. aurantifolia fruit, yielding nanoparticles below 5 nm in size (PDI 0.231 ± 0.04). Characterization revealed favorable optical properties, including excitation-dependent fluorescent behavior with prominent red emission under higher excitation wavelengths, a quantum yield of 8.17%, and stable photoluminescence. Chemical composition analysis using XPS, FTIR, and XRD confirmed the purity and structure of the CDs.To explore their biomedical application, CDs were co-loaded with curcumin into liposomes. The formulations had a mean size of 177.2 ± 3.6 nm (PDI 0.270 ± 0.012), demonstrated efficient drug entrapment (60.32 ± 2.24%), and exhibited rapid release kinetics, with 90.21 ± 2.16% of the drug release within 8 h. In vitro studies using A549 lung cancer cells demonstrated superior cellular uptake and cytotoxicity of Cur-CD-loaded liposomes compared to curcumin alone (Cur-Suspension), achieving IC50 values of 0.093 ± 0.011 µg/ml and 0.016 ± 0.006 µg/ml, respectively.ConclusionThis research underscores C. aurantifolia as a viable natural source for green CD synthesis. The obtained CDs with red fluorescence emission, optimized through reaction conditions and excitation wavelengths, hold promise for enhanced biological applications, particularly in the realm of lung cancer therapy. The findings advocate for further exploration and refinement of citrus-based CDs as versatile theranostic agents, capitalizing on their sustainable origins and potent biomedical properties. The combination of citrus-derived CDs with curcumin loaded into liposomal formulations represents a potent theranostic strategy for lung cancer treatment, leveraging the unique properties of CDs and their potential for targeted and effective therapy.Graphical abstract

Phototactic Biohybrid Microrobot Using Peptide Nanotubes‐Coated Microalgae for pH‐Responsive Active Drug Delivery

Despite the recent wide investigation on active cancer drug delivery, there are still strong medical unmet needs for active tumor‐environment responsive cancer drug delivery in terms of spatiotemporal control. Herein, a biohybrid system of pH‐responsive peptide nanotubes (PNTs)‐coated microalgae for active cancer drug delivery in response to the tumor‐environment is developed. The amphiphilic PNTs are effectively used to encapsulate cancer drugs and coat the living microalgae of C. reinhardtii by electrostatic interactions. The drug‐loaded PNTs‐based biohybrid microalgae maintain agile movement with phototaxis behavior. After in vitro characterization and cytotoxicity assessment, it is shown that the biohybrid microalgae could be phototactically localized to the cancer cells and pH‐responsively disassembled to release cancer drugs in a controlled manner. Finally, with the encapsulation of paclitaxel, the statistically significant suppression of tumor growth in xenograft tumor model animals is successfully demonstrated. Taken together, the feasibility of the multifunctional microrobotic platform for advanced cancer therapy is confirmed.

Catheter ablation vs advanced therapy for patients with severe heart failure and ventricular electrical storm

BackgroundCurrent data on outcomes of an initial strategy of catheter ablation vs advanced therapy in patients with severe heart failure (HF) and electric storm (ES) are limited. ObjectiveThe purpose of this study was to evaluate the outcomes of ventricular tachycardia (VT) ablation vs left ventricular assist device (LVAD) or heart transplantation (HT) in patients with severe HF and ventricular ES. MethodsPatients with severe HF and ES who underwent VT ablation, LVAD, or HT between 2012 and 2022 at our medical center were reviewed. Severe HF was defined as ejection fraction ≤ 35% or presence of severe restrictive, valvular, or genetic cardiomyopathy. We assessed in-hospital adverse events and 1-year outcomes between the 2 groups. ResultsOf the 73 patients, 43 underwent VT ablation and 30 received advanced therapy (21 HT and 9 LVAD). One-year survival was similar (76.7% vs 86.7%; log-rank, P = .308). However, 10 patients (23.3%) in the ablation group underwent HT during follow-up. After multivariable analysis, United Network for Organ Sharing status 1 or 2 by VT criteria (hazard ratio 5.52; 95% confidence interval 1.27–24.12; P = .023) and early VT recurrence (hazard ratio 5.67; 95% confidence interval 1.68–19.09; P = .005) were associated with HT or mortality in patients who underwent VT ablation. ConclusionPatients with severe HF and ES who underwent VT ablation had similar overall survival to patients who directly proceeded with advanced therapy, although rates of HT were high during follow-up. Predictors of HT or mortality after catheter ablation include United Network for Organ Sharing status 1 or 2 by VT criteria and early VT recurrence.

Clinical Characteristics and Outcomes of Patients Suffering Acute Decompensated Heart Failure Complicated by Cardiogenic Shock.

Cardiogenic shock (CS) can stem from multiple causes and portends poor prognosis. Prior studies have focused on acute myocardial infarction-CS; however, acute decompensated heart failure (ADHF)-CS accounts for most cases. We studied patients suffering ADHF-CS to identify clinical factors, early in their trajectory, associated with a higher probability of successful outcomes. Consecutive patients with CS were evaluated (N=1162). We studied patients who developed ADHF-CS at our hospital (N=562). Primary end point was native heart survival (NHS), defined as survival to discharge without receiving advanced HF therapies. Secondary end points were adverse events, survival, major cardiac interventions, and hospital readmissions within 1 year following index hospitalization discharge. Association of clinical data with NHS was analyzed using logistic regression. Overall, 357 (63.5%) patients achieved NHS, 165 (29.2%) died, and 41 (7.3%) were discharged post advanced HF therapies. Of 398 discharged patients (70.8%), 303 (53.9%) were alive at 1 year. Patients with NHS less commonly suffered cardiac arrest, underwent intubation or pulmonary artery catheter placement, or received temporary mechanical circulatory support, had better hemodynamic and echocardiographic profiles, and had a lower vasoactive-inotropic score at shock onset. Bleeding, hemorrhagic stroke, hemolysis in patients with mechanical circulatory support, and acute kidney injury requiring renal replacement therapy were less common compared with patients who died or received advanced HF therapies. After multivariable adjustments, clinical variables associated with NHS likelihood included younger age, history of systemic hypertension, absence of cardiac arrest or acute kidney injury requiring renal replacement therapy, lower pulmonary capillary wedge pressure and vasoactive-inotropic score, and higher tricuspid annular plane systolic excursion at shock onset (all P<0.05). By studying contemporary patients with ADHF-CS, we identified clinical factors that can inform clinical management and provide future research targets. Right ventricular function, renal function, pulmonary artery catheter placement, and type and timing of temporary mechanical circulatory support warrant further investigation to improve outcomes of this devastating condition.