From rare events to systematic data collection: the RESCUED registry for sudden cardiac death in the young in Germany.

BACKGROUND: Approximately one-third of sudden cardiac deaths in the young (SCDY) occur due to a structural cardiac disease. Forty to fifty percent of SCDY cases remain unexplained after autopsy (including microscopic and forensic-toxicological analyses), suggesting arrhythmia syndromes as a possible cause of death. Due to the possible inheritability of these diseases, blood relatives of the deceased may equally be carriers of the causative genetic variations and therefore may have an increased cardiac risk profile. A better understanding of the forensic, clinical, and genetic data might help identify a subset of the general population that is at increased risk of sudden cardiac death. STUDY DESIGN: The German registry RESCUED (REgistry for Sudden Cardiac and UnExpected Death) comprises information about SCDY fatalities and clinical and genetic data of both the deceased and their biological relatives. The datasets collected in the RESCUED registry will allow for the identification of leading causes of SCDY in Germany and offer unique possibilities of scientific analyses with the aim of detecting unrecognized trends, risk factors, and clinical warning signs of SCDY. In a pilot phase of 24 months, approximately 180 SCDY cases (< 50 years of age) and 500 family members and clinical patients will be included. CONCLUSION: RESCUED is the first registry in Germany collecting comprehensive data of SCDY cases and clinical data of the biological relatives reviewed by cardiac experts. RESCUED aims to improve individual risk assessment and public health approaches by directing resources towards early diagnosis and evidence-based, personalized therapy and prevention in affected families. Trial registration number (TRN): DRKS00033543.

[Arrhythmias and amyloidosis]. / Arrhythmien bei Amyloidose.

Cardiac amyloidosis is an infiltrative cardiomyopathy characterized by the extracellular deposition of amyloid fibrils within the myocardium. Beyond heart failure, patients with cardiac amyloidosis commonly present with arrhythmias and conduction system disorders. Atrial fibrillation is observed in up to 80% of patients at the time of diagnosis, with patients typically maintaining normal heart rates due to concurrent atrioventricular nodal disease. The thromboembolic risk is particularly high in patients with cardiac amyloidosis, and left atrial thrombi have been observed even in the absence of atrial fibrillation. Conduction system diseases are also highly prevalent, often necessitating permanent pacemaker implantation. The use of implantable defibrillators in this population remains controversial. This overview of published data and therapeutic strategies related to arrhythmias and conduction system disorders aims to assist readers in decision-making in complex clinical scenarios.

Computer-aided design space identification for screening of protein A affinity chromatography resins.

The rapidly growing market of monoclonal antibodies (mAbs) within the biopharmaceutical industry has incentivised numerous works on the design of more efficient production processes. Protein A affinity chromatography is regarded as one of the best processes for the capture of mAbs. Although the screening of Protein A resins has been previously examined, process flexibility has not been considered to date. Examining performance alongside flexibility is crucial for the design of processes that can handle disturbances arising from the feed stream. In this work, we present a model-based approach for the identification of design spaces, enhanced by machine learning. We demonstrate its capabilities on the design of a Protein A chromatography unit, screening five industrially relevant resins. The computational results favourably compare to experimental data and a resin performance comparison is presented. An improvement on the computational time by a factor of 300,000 is achieved using the machine learning aided methodology. This allowed for the identification of 5,120 different design spaces in only 19 h.

Quality by Design Framework Applied to GMMA Purification.

In recent years, Generalized Modules for Membrane Antigens (GMMA) have received increased attention as an innovative vaccine platform against bacterial pathogens, particularly attractive for low- and middle-income countries because of manufacturing simplicity. The assessment of critical quality attributes (CQAs), product-process interactions, identification of appropriate in process analytical methods, and process modeling is part of a robust quality by design (QbD) framework to support further development and control of manufacturing processes. QbD implementation in the context of the GMMA platform will ensure robust manufacturing of batches with desired characteristics, facilitating technical transfer to local manufacturers, regulatory approval, and commercialization of vaccines based on this technology. Here, we summarize the methodology suggested, applied to a first step of GMMA manufacturing process.

Screening for Occult Transthyretin Amyloidosis in Patients with Severe Aortic Stenosis and Amyloid Red Flags.

AIMS: The optimal strategy to identify transthyretin-type cardiac amyloidosis (ATTR-CA) in patients with aortic stenosis (AS) is still unclear. This study aimed to investigate if targeted screening for ATTR-CA in patients with severe AS and amyloid red flags is associated with higher detection rates. METHODS: The study prospectively enrolled patients ≥65 years with severe AS. Patients who fulfilled ≥1 major (carpal tunnel syndrome (CTS), ruptured biceps tendon, spinal stenosis, N-terminal pro B-type natriuretic peptide ≥1000 pg/mL, cardiac troponin >99th percentile) or ≥2 minor criteria (diastolic dysfunction ≥2 grade/lateral e' <10 cm/s, atrial fibrillation, atrioventricular conduction disease/pacemaker) received bone scintigraphy and biochemical analysis for light chain amyloidosis. Hypertensive patients (>140/90 mmHg) and those with interventricular septal thickness (IVSd) ≤13 mm were excluded. RESULTS: Overall, 264 patients were screened, of whom 85 were included in the analysis. Tracer uptake Perugini grade ≥1 was detected in nine patients (11%). An endomyocardial biopsy was additionally performed in four of nine patients, yielding a prevalence of 7% (n = 6). All patients with dual AS-ATTR were male. Syncope was more commonly reported in AS-ATTR patients (50% vs. 6%, p = 0.010), who also tended to have more severe hypertrophy (IVSd of 18 vs. 16 mm, p = 0.075). Pericardial effusion and CTS were more common in patients with dual pathology (67% vs. 8%, p < 0.001, and 83% vs. 24%, p = 0.003, respectively). CONCLUSION: Targeted screening for ATTR-CA in patients with AS and amyloid red flags does not yield higher detection rates than those reported previously in all comers with AS.

Strategic Planning of a Joint SARS-CoV-2 and Influenza Vaccination Campaign in the UK.

The simultaneous administration of SARS-CoV-2 and influenza vaccines is being carried out for the first time in the UK and around the globe in order to mitigate the health, economic, and societal impacts of these respiratory tract diseases. However, a systematic approach for planning the vaccine distribution and administration aspects of the vaccination campaigns would be beneficial. This work develops a novel multi-product mixed-integer linear programming (MILP) vaccine supply chain model that can be used to plan and optimise the simultaneous distribution and administration of SARS-CoV-2 and influenza vaccines. The outcomes from this study reveal that the total budget required to successfully accomplish the SARS-CoV-2 and influenza vaccination campaigns is equivalent to USD 7.29 billion, of which the procurement costs of SARS-CoV-2 and influenza vaccines correspond to USD 2.1 billion and USD 0.83 billion, respectively. The logistics cost is equivalent to USD 3.45 billion, and the costs of vaccinating individuals, quality control checks, and vaccine shipper and dry ice correspond to USD 1.66, 0.066, and 0.014, respectively. The analysis of the results shows that the choice of rolling out the SARS-CoV-2 vaccine during the vaccination campaign can have a significant impact not only on the total vaccination cost but also on vaccine wastage rate.

Daratumumab in first-line treatment of patients with light chain amyloidosis and Mayo stage IIIb improves treatment response and overall survival.

Treatment of patients with Mayo stage IIIb light chain (AL) amyloidosis is still challenging, and the prognosis remains very poor. Mayo stage IIIb patients were excluded from the pivotal trial leading to the approval of daratumumab in combination with bortezomib-cyclophosphamide-dexamethasone. This retrospective, multicenter study evaluates the addition of daratumumab to first-line therapy in patients with newly diagnosed stage IIIb AL amyloidosis. In total, data from 119 consecutive patients were analyzed, 27 patients received an upfront treatment including daratumumab, 63 a bortezomibbased regimen without daratumumab, eight received therapies other than daratumumab or bortezomib and 21 pretreated patients or deceased prior to treatment were excluded. In the daratumumab group, median overall survival was not reached after a median follow-up time of 14.5 months, while it was significantly worse in the bortezomib- and the otherwise treated group (6.6 and 2.2 months, respectively) (P=0.002). Overall hematologic response rate at 2 and 6 months was better in the daratumumab group compared to the bortezomib group (59% vs. 37%, P=0.12, 67% vs. 41%, P=0.04, respectively). Landmark survival analyses revealed a significantly improved overall survival in patients with partial hematologic response or better, compared to non-responders. Cardiac response at 6 months was 46%, 21%, 0% in the daratumumab-, bortezomib- and otherwise treated groups, respectively (P=0.04). A landmark survival analysis revealed markedly improved overall survival in patients with cardiac very good partial response vs. cardiac non-responders (P=0.002). This study demonstrates for the first time the superiority of an upfront treatment with daratumumab over standard-of-care in stage IIIb AL amyloidosis.

Uncertainty quantification for gene delivery methods: A roadmap for pDNA manufacturing from phase I clinical trials to commercialization.

The fast-growing interest in cell and gene therapy (C>) products has led to a growing demand for the production of plasmid DNA (pDNA) and viral vectors for clinical and commercial use. Manufacturers, regulators, and suppliers need to develop strategies for establishing robust and agile supply chains in the otherwise empirical field of C>. A model-based methodology that has great potential to support the wider adoption of C> is presented, by ensuring efficient timelines, scalability, and cost-effectiveness in the production of key raw materials. Specifically, key process and economic parameters are identified for (1) the production of pDNA for the forward-looking scenario of non-viral-based Chimeric Antigen Receptor (CAR) T-cell therapies from clinical (200 doses) to commercial (40,000 doses) scale and (2) the commercial (40,000 doses) production of pDNA and lentiviral vectors for the current state-of-the-art viral vector-based CAR T-cell therapies. By applying a systematic global sensitivity analysis, we quantify uncertainty in the manufacturing process and apportion it to key process and economic parameters, highlighting cost drivers and limitations that steer decision-making. The results underline the cost-efficiency and operational flexibility of non-viral-based therapies in the overall C> supply chain, as well as the importance of economies-of-scale in the production of pDNA.

Inactivation of Tumor Suppressor CYLD Inhibits Fibroblast Reprogramming to Pluripotency.

CYLD is a tumor suppressor gene coding for a deubiquitinating enzyme that has a critical regulatory function in a variety of signaling pathways and biological processes involved in cancer development and progression, many of which are also key modulators of somatic cell reprogramming. Nevertheless, the potential role of CYLD in this process has not been studied. With the dual aim of investigating the involvement of CYLD in reprogramming and developing a better understanding of the intricate regulatory system governing this process, we reprogrammed control (CYLDWT/WT) and CYLD DUB-deficient (CYLDΔ9/Δ9) mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs) through ectopic overexpression of the Yamanaka factors (Oct3/4, Sox2, Klf4, c-myc). CYLD DUB deficiency led to significantly reduced reprogramming efficiency and slower early reprogramming kinetics. The introduction of WT CYLD to CYLDΔ9/Δ9 MEFs rescued the phenotype. Nevertheless, CYLD DUB-deficient cells were capable of establishing induced pluripotent colonies with full spontaneous differentiation potential of the three germ layers. Whole proteome analysis (Data are available via ProteomeXchange with identifier PXD044220) revealed that the mesenchymal-to-epithelial transition (MET) during the early reprogramming stages was disrupted in CYLDΔ9/Δ9 MEFs. Interestingly, differentially enriched pathways revealed that the primary processes affected by CYLD DUB deficiency were associated with the organization of the extracellular matrix and several metabolic pathways. Our findings not only establish for the first time CYLD's significance as a regulatory component of early reprogramming but also highlight its role as an extracellular matrix regulator, which has profound implications in cancer research.

Caplacizumab for immune thrombotic thrombocytopenic purpura: real-world multicenter data.

Given the limited real-world data of caplacizumab, our multicenter real-world study was designed to assess the safety and efficacy of caplacizumab in immune thrombotic thrombocytopenic pupura (iTTP), compared to historic controls. We have studied 70 patients: 23 in the caplacizumab and 47 in the historic control group. Plasma exchange was applied in all episodes except for two patients that denied plasma exchange. Rituximab as first-line treatment was more common in the caplacizumab group compared to historic control. Caplacizumab (10 mg daily) was given at a median on day 7 (1-43) from initial diagnosis for 32 (6-47) dosages. In the caplacizumab group, a median of 12 (8-23) patients required plasma exchange sessions versus 14 (6-32) in the control group. Caplacizumab administration did not produce any grade 3 complications or major hemorrhagic events. After a median of 19.0 (2.6-320) months since the iTTP diagnosis, 5 deaths occurred (4 in the control group and 1 in the caplacizumab group, p = 0.310). Caplacizumab patients achieved early platelet normalization and ADAMTS13 activity normalization at the end of treatment. Relapse was observed only in 2/23 (9%) caplacizumab patients, compared to 29/47 (62%) historic controls (p < 0.001). Overall, caplacizumab is safe and effective in treating iTTP, including cases refractory to plasma exchange, re-administration, and cases without previous plasma exchange treatment. No major hemorrhagic events were observed. Cessation of dosing guided by ADAMTS13 has ensured a low relapse rate.

Erectile dysfunction and quality of life in patients under left ventricular assist device support - an unspoken issue.

Background: Multiple domains of quality of life (QoL) such as erectile function are not sufficiently investigated among left ventricular assist-device (LVAD) patients. We aimed to evaluate the prevalence of erectile dysfunction (ED) and its association with QoL and depression. Methods: This is a prospective, single-center, cross-sectional study. We included adult male LVAD patients who were clinically stable after at least 3 months post-implantation. Erectile function was assessed with the International Index of Erectile Function (IIEF-5) questionnaire with a score of ≤21 being confirmatory for ED. QoL and depression were estimated with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Patient Health Questionnaire depression scale (PHQ-8), respectively. Results: The study included 56 patients, of whom 45 (80 %) met criteria for ED, a prevalence much higher than previously reported in patients with established cardiovascular disease or conservatively treated heart failure. Patients with ED were older and had lower 6-minute walking distance. ED was not associated with comorbidities and heart failure medications but with less frequent use of diuretics and phosphodiesterase-5 inhibitors. There was a correlation between erectile function and depression as well as QoL. Conclusions: These findings underscore that ED deserves special attention and should be included in a multi-targeted approach to address suboptimal QoL outcomes after LVAD implantation.

Endoscopic Plantar Fasciotomy as an Effective and Reliable Treatment for Plantar Fasciitis: An Overview of the Literature.

Plantar fasciitis is a common cause of heel pain. The aim of this study was to review the current literature and attempt to clarify whether endoscopic plantar fasciotomy (EPF) is an effective and reliable treatment for plantar fasciitis in comparison with other invasive or noninvasive treatments. We performed an electronic search of the medical literature in PubMed database using combinations of the following keywords: plantar fasciitis, endoscopic treatment, and plantar aponeurosis. Overall, we had shown that patients had better scores following EPF/endoscopic plantar fascia release. The clinical scores were improved postoperatively and most of the patients were satisfied. Furthermore, the clinical trials showed that time to return to work or to previous activities was shorter compared with other treatments. These studies suggest that EPF/endoscopic plantar fascia release is probably an effective treatment of chronic plantar fasciitis. EPF is an efficient, safe treatment with good early postoperative results in patients with recalcitrant plantar fasciitis. There is evidence that other methods are equivalently effective for EPF, and some authors support that they should be considered as a second-line treatment because of their minimal invasive character and very low risk of complications; thus, more research is required.

Diastolic exercise stress testing in heart failure with preserved ejection fraction: The DEST-HF study.

AIMS: Pulmonary capillary wedge pressure (PAWP) ≥25 mmHg during bicycle ergometry is recommended to uncover occult heart failure with preserved ejection fraction. We hypothesized that PAWP increase would differ in available diastolic stress tests and that the margin of PAWP ≥25 mmHg would only be reliably achieved through ergometry. METHODS AND RESULTS: We conducted a prospective, single-arm study in patients with an intermediate risk for heart failure with preserved ejection fraction according to the ESC HFA-PEFF score. A total of 19 patients underwent four stress test modalities in randomized order: leg raise, fluid challenge, handgrip, and bicycle ergometry. The primary outcome was the difference (Δ) between resting and exercise PAWP in each modality. Secondary outcomes were differences (Δ) in mean pulmonary artery pressure (mPAP), cardiac output (CO), as well as the ratios between mPAP and PAWP to CO. Compared to resting values, passive leg raise (Δ7.7 ± 8.0 mmHg, p = 0.030), fluid challenge (Δ9.2 ± 6.4 mmHg, p = 0.003), dynamic handgrip (Δ9.6 ± 7.5 mmHg, p = 0.002), and bicycle ergometry (Δ22.3 ± 5.0 mmHg, p < 0.001) uncovered increased PAWP during exercise. Amongst these, bicycle ergometry also demonstrated the highest ΔmPAP (27.2 ± 7.1 mmHg, p < 0.001), ΔCO (3.3 ± 2.6 L/min, p < 0.001), ΔmPAP/CO ratio (2.3 ± 2.0 mmHg/L/min, p < 0.001), and ΔPAWP/CO ratio (2.2 ± 1.4 mmHg/L/min, p < 0.001) compared to other modalities. PAWP ≥25 mmHg was only reliably achieved in bicycle ergometry (31.1 ± 3.9 mmHg). In all other modalities only 10.5% of patients achieved PAWP ≥25 mmHg (handgrip 18.4 ± 6.6 mmHg, fluid 18.1 ± 5.6 mmHg, leg raise 16.5 ± 7.0 mmHg). CONCLUSIONS: We demonstrate that bicycle ergometry exhibits a distinct haemodynamic response with higher increase of PAWP compared to other modalities. This finding needs to be considered for valid detection of exercise PAWP ≥25 mmHg when non-bicycle tests remain inconclusive.

Regression of Myocardial 99mTc-DPD Uptake After Tafamidis Treatment of Cardiac Transthyretin Amyloidosis.

Cardiac transthyretin amyloidosis is an infiltrative cardiomyopathy with high mortality. To date, there are no specific biomarkers to directly assess disease activity and response to specific treatments. Our aim was to evaluate scintigraphic changes after treatment with the transthyretin stabilizer tafamidis. Methods: We included patients who had undergone 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy before tafamidis initiation and after at least 9 mo. Tracer activity was assessed visually and quantitatively as SUVmax Results: The study included 14 patients who were on tafamidis for 44 ± 14 mo. We observed regression of Perugini grade in 5 patients, unchanged grade in 9 patients, and regression of mean heart-to-contralateral-lung ratio (P = 0.015) and SUVmax (P = 0.005). There were no changes in N-terminal pro-B-type natriuretic peptide or echocardiographic measures. Conclusion: Treatment with tafamidis results in regression of myocardial 99mTc-DPD uptake. 99mTc-DPD scintigraphy may provide useful imaging biomarkers to assess response to treatment.

Vascular complications after peripheral veno-arterial extracorporeal life support cannulation in cardiogenic shock.

Background: Extra Corporeal Life Support (ECLS) is an evolving therapy in therapy-resistant cardiogenic shock (CS). Vascular cannulation in emergency situations can be accomplished through puncture of the femoral vessels by specialised teams. Since lower limb ischemia constitutes one of the major complications following cannulation, a distal perfusion cannula (DPC) has emerged as standard of care. We here aimed to analyse the impact of the DPC on limb perfusion and 6-month survival rate. Methods: In a retrospective study from January 2012 to December 2018, 98 patients with cardiogenic shock and peripheral (v-a) ECLS implantation with documented limb perfusion status were identified and analysed. Demographic data, laboratory parameters, cause of CS, comorbidities, limb perfusion complications and complication management were analysed. Results: 53 patients (54%) received ECLS therapy in referral centers by our mobile ECLS team, while in 45 patients (46%) the cannulation occured in our center. 71 patients (72%) received a DPC (group A) at the time of ECLS implantation, whereas 27 (28%) (group B) did not or received later (14 patients owing to limb ischemia). 44 patients (45%) developed limb ischemia as a complication of ECLS therapy (31% in group A and 81% in group B- p < 0.001). The 6-month survival rate was 28% in our study cohort (30% in group A and 22% in group B- p = 0.469). Conclusion: Lower limb ischemia remains a serious complication after peripheral ECLS cannulation in CS, especially when a DPC is absent. Standardised DPC implementation may reduce the rate of severe limb complications in peripheral ECLS.

Introduction of machine perfusion of donor hearts in a single center in Germany.

Introduction: Organ shortage, subsequent use of extended donor criteria organs and high-risk recipients needing redo-surgery are increasing the complexity of heart transplantation. Donor organ machine perfusion (MP) is an emerging technology allowing reduction of ischemia time as well as standardized evaluation of the organ. The aim of this study was to review the introduction of MP and analyze the results of heart transplantation after MP in our center. Methods: In a retrospective single-center study, data from a prospectively collected database were analysed. From July 2018 to August 2021, fourteen hearts were retrieved and perfused using the Organ Care System (OCS), 12 hearts were transplanted. Criteria to use the OCS were based on donor/recipient characteristics. Primary objective was 30-day survival, secondary objectives were major cardiac adverse events, graft function, rejection episodes as well as overall survival in the follow-up and assessment of MP technical reliability. Results: All patients survived the procedure and the postoperative 30-day interval. No MP related complications were noted. Graft ejection fraction beyond 14 days was ≥ 50% in all cases. Endomyocardial biopsy showed excellent results with no or mild rejection. Two donor hearts were rejected after OCS perfusion and evaluation. Conclusion: Ex vivo normothermic MP during organ procurement is a safe and promising technique to expand the donor pool. Reduction of cold ischemic time while providing additional donor heart assessment and reconditioning options increased the number of acceptable donor hearts. Additional clinical trials are necessary to develop guidelines regarding the application of MP.

Septal Microsphere Embolization in Hypertrophic Obstructive Cardiomyopathy.

Alcohol septal ablation is an established treatment for selected patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction (LVOT). The safety and efficacy of septal microsphere embolization (SME) have not been studied. We conducted a retrospective analysis of SME procedures performed at our center from 2006 to 2021 using 75-µm microspheres. The primary end point was LVOT gradient reduction. Secondary outcomes included periprocedural mortality, conduction disturbances, access site complications, and duration of hospitalization. The population comprised 76 patients (median age 61 years, men 43%). Dyspnea New York Heart Association ≥III was present in 65 patients (86%); ventricular tachycardia and previous syncope were described in 4% and 18%, respectively. Median duration of hospitalization was 13 days, and the time to first follow-up was 4 months. SME resulted in a significant reduction at rest (41 vs 12 mm Hg, mean Δ PG = -71%, p <0.001) and provoked LVOT gradients (94 vs 29 mm Hg, mean Δ PG = -75%, p <0.001). Periprocedural death occurred in 1 patient (1%) who underwent SME after transcatheter aortic valve replacement. Complete atrioventricular block was observed in 5 patients (7%). Left bundle branch block was diagnosed in 1 case (1%) and right bundle branch block in 3 (4%). Access site complications were observed in 4 patients (5%). In conclusion, SME is a safe and effective alternative to alcohol septal ablation. The potential advantages of microspheres are still to be investigated in prospective studies.

Central extracorporeal circulatory life support (cECLS) in selected patients with critical cardiogenic shock.

Background: Percutaneous extracorporeal life support (pECLS) is increasingly applied in cardiogenic shock (CS) despite a lack of evidence from randomized trials. The in-hospital mortality rate of pECLS still reaches up to 60%, while vascular access site complications remain a shortcoming. Surgical approaches with central cannulation for ECLS (cELCS) have emerged as a bail-out option. To date, no systematic approach exists that allows a definition of inclusion or exclusion criteria for cECLS. Methods and results: This single-center, retrospective, case-control study includes all patients fulfilling criteria for CS at the West German Heart and Vascular Center Essen/Germany between 2015 and 2020 who underwent cECLS (n = 58), excluding post-cardiotomy patients. Seventeen patients received cECLS (29.3%) as a first-line treatment strategy and 41 patients as a second-line strategy (70.7%). The main complications leading to the use of cECLS as a second-line strategy were limb ischemia (32.8%) and ongoing insufficient hemodynamic support (27.6%). The first-line cECLS cohort showed a 30-day mortality rate of 53.3% that was constant during follow-up. The 30-day mortality rate of secondary cECLS candidates was 69.8% and the rate at 3 and 6 months was 79.1%. Younger patients (<55 years) were more likely to exhibit survival benefit with cECLS (p = 0.043). Conclusion: Surgical cECLS in CS is a feasible therapy for highly selected patients with hemodynamic instability, vascular complications, or peripheral access site limitations as complementary strategy in experienced centers.

Sex-Related Differences among Adults with Hypertrophic Obstructive Cardiomyopathy Undergoing Transcoronary Ablation of Septal Hypertrophy.

(1) Background: The transcoronary ablation of septal hypertrophy (TASH) is an established therapy for hypertrophic obstructive cardiomyopathy (HOCM). Previous studies on this topic are characterised by a consistent male predominance and show a worse prognosis in females. (2) Methods: This study is a retrospective analysis of all TASH procedures conducted between 2006 and 2021 at a tertiary academic centre. A solution of 75 µm microspheres (Embozene®, Boston Scientific, Marlborough, MA, USA) was used as an embolising agent. The outcomes of interest were left ventricular outflow tract (LVOT) gradient reduction and symptom improvement among males vs. that among females. Secondarily, we analysed the sex-related differences in procedural safety outcomes and mortality. (3) Results: The study population consisted of 76 patients, with a median age of 61 years. Females comprised 57% of the cohort. We observed no sex-related differences in the baseline LVOT gradients at rest or under provocation (p = 0.560 and p = 0.208, respectively). Females were significantly older at the time of the procedure (p < 0.001), had lower tricuspid annular systolic excursion (TAPSE) (p = 0.009), presented a worse clinical status according to the NYHA functional classification (for NYHA ≥ 3, p < 0.001), and were more often on diuretics (p < 0.001). We did not observe sex-related differences in absolute gradient reduction at rest (p = 0.147) and under provocation (p = 0.709). There was a reduction in the NYHA class by a median value of 1 (p = 0.636) at follow-up for both sexes. Postprocedural access site complications were documented in four cases (two of which concerned females), and complete atrioventricular block was noted in five patients (three of which concerned females). The 10-year survival rates were comparable between the sexes (85% in females and 88% in males). The female sex was not associated with enhanced mortality according to multivariate analysis after adjusting for the confounding variables (HR 0.94; 95% CI 0.376-2.350; p = 0.895), but we observed age-related differences in long-term mortality (HR 1.035; 95% CI 1.007-1.063; p = 0.015). (4) Conclusions: TASH is safe and effective in both sexes, irrespective of their clinical differences. Women present at an advanced age and with more severe symptoms. An advanced age at the time of the intervention is an independent predictor of mortality.