A streamlined pathway for transcatheter aortic valve implantation: the BENCHMARK study.

BACKGROUND AND AIMS: There is significant potential to streamline the clinical pathway for patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the effect of implementing BENCHMARK best practices on the efficiency and safety of TAVI in 28 sites in 7 European countries. METHODS: This was a study of patients with severe symptomatic aortic stenosis (AS) undergoing TAVI with balloon-expandable valves before and after implementation of BENCHMARK best practices. Principal objectives were to reduce hospital length of stay (LoS) and duration of intensive care stay. Secondary objective was to document patient safety. RESULTS: Between January 2020 and March 2023, 897 patients were documented prior to and 1491 patients after the implementation of BENCHMARK practices. Patient characteristics were consistent with a known older TAVI population and only minor differences. Mean LoS was reduced from 7.7 ± 7.0 to 5.8 ± 5.6 days (median 6 vs. 4 days; P < .001). Duration of intensive care was reduced from 1.8 to 1.3 days (median 1.1 vs. 0.9 days; P < .001). Adoption of peri-procedure best practices led to increased use of local anaesthesia (96.1% vs. 84.3%; P < .001) and decreased procedure (median 47 vs. 60 min; P < .001) and intervention times (85 vs. 95 min; P < .001). Thirty-day patient safety did not appear to be compromised with no differences in all-cause mortality (0.6% in both groups combined), stroke/transient ischaemic attack (1.4%), life-threatening bleeding (1.3%), stage 2/3 acute kidney injury (0.7%), and valve-related readmission (1.2%). CONCLUSIONS: Broad implementation of BENCHMARK practices contributes to improving efficiency of TAVI pathway reducing LoS and costs without compromising patient safety.

Lipoprotein(a) as a risk factor for atherosclerotic cardiovascular disease in patients in non-metropolitan areas of Brandenburg, Germany.

Background and aims: In the non-metropolitan region of Brandenburg (Germany), which is characterized by high rates of cardiovascular diseases and underserved medical care, there is a lack of awareness regarding lipoprotein(a) [Lp(a)] as a risk factor. In addition, data from patients with atherosclerotic cardiovascular disease (ASCVD) in diverse regional backgrounds, including the understudied Brandenburg cohort, and various healthcare statuses remain insufficient. Methods: In this WalkByLab study, Lp(a) levels were monitored in a non-metropolitan cohort (n = 850) in Brandenburg, Germany, comprising 533 patients at high cardiovascular risk and 317 healthy controls. Patients underwent a comprehensive angiological screening, which included blood serum analysis, assessment of medical and family history, cardiovascular risk, and disease status, and evaluation of lifestyle and quality of life. All parameters were evaluated with regard to two groups based on Lp(a) levels: low (<50 mg/dl) and high (≥50 mg/dl). Results: Brandenburg patients with cardiovascular diseases showed higher Lp(a) levels than healthy controls (24.2% vs. 14.8%, p = 0.001). Logistic regression analysis with different characteristics revealed that Lp(a) was an independent risk factor significantly associated with ASCVD (OR 2.26, 95% CI 1.32-3.95, p = 0.003). The high-Lp(a) group showed a higher proportion of patients with coronary artery disease, peripheral artery disease, or cerebrovascular disease compared to the low-Lp(a) group (50% vs. 36.8%; 57.7% vs. 45.8%; 17.6% vs. 9.2%; p = 0.004); also, a higher percentage of patients in the high-Lp(a) group had heart failure (72.8% vs. 53.2%, p = 0.014) and myocardial infarction (24.7% vs. 13.9%, p = 0.001). The high-Lp(a) group exhibited higher rates of statins (63.1% vs. 50.4%, p = 0.003), ezetimibe (14.8% vs. 5.5.%, p = 0.001), and beta-blockers (55.7% vs. 40.7%, p = 0.001) use. Lp(a) levels were found to be independent of physical activity or smoking behavior and did not change over time (12 months). Conclusions: Our study highlights the significance of elevated Lp(a) levels in Brandenburg cardiovascular patients and identifies them as an independent risk factor for ASCVD, which has implications for addressing cardiovascular health of non-metropolitan populations.

Patterns of aortic valve replacement in Europe and adoption by sex.

OBJECTIVE: Management of patients with severe aortic stenosis (AS) may differ according to the patient sex. This study aimed to describe patterns of aortic valve replacement (AVR) for severe AS across Europe, including stratification by sex. METHODS: Procedure volume data for surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) for six years (2015-2020) were extracted from national databases for Austria, Czech Republic, Denmark, England, Finland, France, Germany, Norway, Poland, Spain, Sweden, and Switzerland and stratified by sex. Patients per million population (PPM) undergoing AVR per year were calculated using population estimates from Eurostat. RESULTS: Between 2015 and 2019, AVR procedures grew at an average annual rate of 3.9%. In 2020, the average total PPM undergoing AVR across all countries was 339, with 51% of procedures being TAVI and 49% SAVR. AVR PPM varied widely between countries, with the highest and lowest in Germany and Poland, respectively. The average total PPM was higher for men than women (423 vs. 258), but a higher proportion of women (62%) than men (44%) received TAVI. The proportion of TAVI among total AVR procedures increased with age, with an overall average of 96% of men and 98% of women aged ≥85 years receiving TAVI; however, adoption of TAVI varied by country. CONCLUSIONS: The analysis of temporal trends in the adoption of TAVI vs. SAVR across Europe showed significant variations. Despite the higher use of TAVI vs. SAVR in women, overall rates of AV intervention in women were lower compared to men.

Outcomes of patients undergoing edge-to-edge mitral valve repair with the Edwards PASCAL transcatheter valve repair system under conscious sedation.

BACKGROUND: The development of the PASCAL transcatheter valve repair system for treating mitral regurgitation (MR) greatly extends therapeutic options. AIMS: To assess the safety, efficacy, and time efficiency of the PASCAL system in transcatheter edge-to-edge repair (TEER) under conscious sedation (CS). METHODS: This is a retrospective, two-center, German registry study consisting of 211 patients who underwent TEER using the PASCAL system under CS. The endpoints were to assess (1) technical, device, and procedural success as per Mitral Valve Academic Research Consortium (MVARC), (2) conversion rate to general anesthesia (GA), (3) hospital length of stay (LoS), (4) New York Heart Association (NYHA) class, and (5) MR compared to baseline at 30-day. RESULTS: A total of 211 patients with a mean age of 78.4 ± 8.9 years, with 51.4% being female and 86.7% belonging to NYHA functional class III/IV and EuroSCORE II 6.3 ± 4.9%, were enrolled. Procedural success attained was 96.9%, and six patients (2.8%) required conversion from CS to GA. At 30 days follow-up, a significant improvement in MR was found in 96 patients (54.2%) patients with 0/1 grade MR and 45 patients (29.5%) were in NYHA functional class III + IV. Moreover, TEER under CS has a short hospital LoS (6.71 ± 5.29 days) and intensive care unit LoS (1.34 ± 3.49 days) with a 2.8% mortality rate. CONCLUSIONS: Performing TEER with the PASCAL system under CS resulted in appreciable (96.9%) procedural success with low mortality and is a safe and promising alternative to GA with positive clinical outcomes.

Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in type 1 diabetes and type 2 diabetes: Lipid goal attainment in a large German-Austrian diabetes registry.

AIM: To assess the implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline recommendations for lipid-lowering therapies among more than 30 000 patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) in a German and Austrian registry from 2020 to 2022. MATERIALS AND METHODS: Registry data from 2020 and 2021 of 32 170 adult patients (8314 patients with T1D and 23 856 with T2D) were stratified according to the 2019 ESC/EAS risk categories, and guideline-based low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) goal attainment was analysed. RESULTS: In patients with T1D (median age 38.35 [20.51-57.13] years), overall statin use was 19.3%, ezetimibe use was 2.2% and the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors or fibrates was less than 1%. In patients with T2D (median age 68.76 [58.86-78.39] years), 45.7% received statins, 3.4% received ezetimibe, and fibrates and PCSK9 inhibitors were used by 1% and 0.1%, respectively. Among patients with T1D, 6.16% reached their risk-based recommended LDL-C goal of less than 55 mg/dL (very high risk), 10.97% of less than 70 mg/dL (high risk), and 69.50% of less than 100 mg/dL (moderate risk), respectively. In patients with T2D, 11.81% reached their risk-based goal of LDL-C less than 55 mg/dL, 16.25% of less than 70 mg/dL, and 51.33% of less than 100 mg/dL. Non-HDL-C goals were reached more often, with 15.3%, 25.52% and 91.61% in patients with T1D and 18.56%, 17.96% and 82.30% in patients with T2D for very high, high and moderate risk, respectively. CONCLUSION: Approximately 2 years after publication of the guidelines, LDL-C and non-HDL-C goal attainment was rarely achieved in patients with T1D and T2D with a high or very high cardiovascular risk.

Intraoperative hypotension when using hypotension prediction index software during major noncardiac surgery: a European multicentre prospective observational registry (EU HYPROTECT).

Background: Intraoperative hypotension is associated with organ injury. Current intraoperative arterial pressure management is mainly reactive. Predictive haemodynamic monitoring may help clinicians reduce intraoperative hypotension. The Acumen™ Hypotension Prediction Index software (HPI-software) (Edwards Lifesciences, Irvine, CA, USA) was developed to predict hypotension. We built up the European multicentre, prospective, observational EU HYPROTECT Registry to describe the incidence, duration, and severity of intraoperative hypotension when using HPI-software monitoring in patients having noncardiac surgery. Methods: We enrolled 749 patients having elective major noncardiac surgery in 12 medical centres in five European countries. Patients were monitored using the HPI-software. We quantified hypotension using the time-weighted average MAP <65 mm Hg (primary endpoint), the proportion of patients with at least one ≥1 min episode of a MAP <65 mm Hg, the number of ≥1 min episodes of a MAP <65 mm Hg, and duration patients spent below a MAP of 65 mm Hg. Results: We included 702 patients in the final analysis. The median time-weighted average MAP <65 mm Hg was 0.03 (0.00-0.20) mm Hg. In addition, 285 patients (41%) had no ≥1 min episode of a MAP <65 mm Hg; 417 patients (59%) had at least one. The median number of ≥1 min episodes of a MAP <65 mm Hg was 1 (0-3). Patients spent a median of 2 (0-9) min below a MAP of 65 mm Hg. Conclusions: The median time-weighted average MAP <65 mm Hg was very low in patients in this registry. This suggests that using HPI-software monitoring may help reduce the duration and severity of intraoperative hypotension in patients having noncardiac surgery.

Patterns of Aortic Valve Replacement in Europe: Adoption by Age.

INTRODUCTION: The management of patients with severe aortic stenosis may differ according to patients' age. The aim of this analysis was to describe patterns of aortic valve replacement (AVR) use in European countries stratified by age. METHODS: Procedure volume data for AVR, including surgical aortic valve replacement (sAVR) and transcatheter aortic valve implantation (TAVI), for the years 2015-2020 were obtained from national databases for twelve European countries (Austria, the Czech Republic, Denmark, England, Finland, France, Germany, Norway, Poland, Spain, Sweden, and Switzerland). Procedure volumes were reported by patient age (<50 years, 5-year age groups between 50 and 85 years, and ≥85 years). Patients per million (PPM) population undergoing AVR each year were calculated using population estimates from Eurostat. RESULTS: AVR PPM varied widely between countries, from 508 PPM in Germany to 174 PPM in Poland in 2020. TAVI rates ranged from 61% in Switzerland and Finland to 25% in Poland. AVR PPM increased with age to a peak at 80-84 years, after which it decreased again. AVR procedures increased from 2015 to 2019 at an average annual rate of 3.9%. AVR increased more substantially in people aged ≥80 years than in younger age groups; these older age groups accounted for 30% of all AVR procedures in 2015 and 35% in 2019. TAVI accounted for an increasing proportion of all AVR procedures as patient age increased; an overall average of 96% of males and 98% of females aged ≥85 years received TAVI as the treatment modality, although adoption of TAVI differed between countries. CONCLUSIONS: There is considerable variation in the rates of AVR use and the adoption of TAVI versus sAVR between European countries. The use of TAVI has increased in recent years, particularly for older patients.

Durability of bioprosthetic aortic valve replacement in patients under the age of 60 years - 1-year follow-up from the prospective INDURE registry.

OBJECTIVES: We report 1-year safety and clinical outcomes in patients <60 years undergoing bioprosthetic surgical aortic valve intervention. METHODS: The INSPIRIS RESILIA Durability Registry is a prospective, multicentre registry to assess clinical outcomes of patients <60 years. Patients with planned SAVR with or without concomitant replacement of the ascending aorta and/or coronary bypass surgery were included. Time-related valve safety, haemodynamic performance and quality of life (QoL) at 1 year were assessed. RESULTS: A total of 421 patients were documented with a mean age of 53.5 years, 76.5% being male and 27.2% in NYHA class III/IV. Outcomes within 30 days included cardiovascular-related mortality (0.7%), time-related valve safety (VARC-2; 5.8%), thromboembolic events (1.7%), valve-related life-threatening bleeding (VARC-2; 4.3%) and permanent pacemaker implantation (3.8%). QoL was significantly increased at 6 months and sustained at 1 year. Freedom from all-cause mortality at 1 year was 98.3% (95% confidence interval 97.1; 99.6) and 81.8% were NYHA I versus 21.9% at baseline. No patient developed structural valve deterioration stage 3 (VARC-3). The mean aortic pressure gradient was 12.6 mmHg at 1 year and the effective orifice area was 1.9 cm2. CONCLUSIONS: The 1-year data from the INSPIRIS RESILIA valve demonstrate good safety and excellent haemodynamic performance as well as an early QoL improvement. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT03666741.

Quality of Life Measures in Aortic Stenosis Research: A Narrative Review.

BACKGROUND: Elderly patients with aortic stenosis (AS) not only have a reduced life expectancy but also a reduced quality of life (QoL). The benefits of an AS intervention may be considered a balance between a good QoL and a reasonably extended life. However, the different questionnaires being used to determine the QoL were generally not developed for the specific situation of patients with AS and come with strengths and considerable weaknesses. The objective of this article was to provide an overview of the available QoL instruments in AS research, describe their strengths and weaknesses, and provide our assessment of the utility of the available scoring instruments for QoL measurements in AS. SUMMARY: We identified and reviewed the following instruments that are used in AS research: Short Form Health Survey (SF-36/SF-12), EuroQol-5D (EQ-5D), the Illness Intrusiveness Rating Scale (IIRS), the HeartQoL, the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Minnesota Living with Heart Failure Questionnaire (MLHF), the MacNew Questionnaire, and the Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ). KEY MESSAGES: There is no standardized assessment of QoL in patients with AS. Many different questionnaires are being used, but they are rarely specific for AS. There is a need for AS-specific research into the QoL of patients as life prolongation may compete for an improved QoL in this elderly patient group.

Is the outcome of elective vs non-elective patients undergoing transcatheter aortic valve implantation different? Results of a single-centre, observational assessment of outcomes at a large university clinic.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) can either be conducted as an elective (scheduled in advance) or a non-elective procedure performed during an unplanned hospital admission. The objective of this study was to compare the outcomes of elective and non-elective TAVI patients. METHODS: This single-centre study included 512 patients undergoing transfemoral TAVI between October 2018 and December 2020; 378 (73.8%) were admitted for elective TAVI, 134 (26.2%) underwent a non-elective procedure. Our TAVI programme entails an optimized fast-track concept aimed at minimizing the total length of stay to ≤ 5 days for elective patients which in the German healthcare system is currently defined as the minimal time period to safely perform TAVI. Clinical characteristics and survival rates at 30 days and 1 year were analysed. RESULTS: Patients who underwent non-elective TAVI had a significantly higher comorbidity burden. Median duration from admission to discharge was 6 days (elective group 6 days versus non-elective group 15 days; p < 0.001), including a median postprocedural stay of 5 days (elective 4 days versus non-elective 7 days; p < 0.001). All-cause mortality at 30 days was 1.1% for the elective group and 3.7% for non-elective patients (p = 0.030). At 1 year, all-cause mortality among elective TAVI patients was disproportionately lower than in non-elective patients (5.0% versus 18.7%, p < 0.001). In the elective group, 54.5% of patients could not be discharged early due to comorbidities or procedural complications. Factors associated with a failure of achieving a total length of stay of ≤ 5 days comprised frailty syndrome, renal impairment as well as new permanent pacemaker implantation, new bundle branch block or atrial fibrillation, life-threatening bleeding, and the use of self-expanding valves. After multivariate adjustment, new permanent pacemaker implantation (odds ratio 6.44; 95% CI 2.59-16.00), life-threatening bleeding (odds ratio 4.19; 95% confidence interval 1.82-9.66) and frailty syndrome (odds ratio 5.15; 95% confidence interval 2.40-11.09; all p < 0.001, respectively) were confirmed as significant factors. CONCLUSIONS: While non-elective patients had acceptable periprocedural outcomes, mortality rates at 1 year were significantly higher compared to elective patients. Approximately only half of elective patients could be discharged early. Improvements in periprocedural care, follow-up strategies and optimized treatment of both elective and non-elective TAVI patients are needed.

Subannular repair in secondary mitral regurgitation with restricted leaflet motion during systole.

OBJECTIVE: Ventricular secondary mitral regurgitation (SMR) (Carpentier type IIIb) results from left ventricular (LV) remodelling, displacement of papillary muscles and tethering of mitral leaflets. The most appropriate treatment approach remains controversial. We aimed to assess the safety and efficacy of standardised relocation of both papillary muscles (subannular repair) at 1-year follow-up (FU). METHODS: REFORM-MR (Reform-Mitral Regurgitation) is a prospective, multicentre registry that enrolled consecutive patients with ventricular SMR (Carpentier type IIIb) undergoing standardised subannular mitral valve (MV) repair in combination with annuloplasty at five sites in Germany. Here, we report survival, freedom from recurrence of MR >2+, freedom from major adverse cardiac and cerebrovascular events (MACCEs), including cardiovascular death, myocardial infarction, stroke, MV reintervention and echocardiographic parameters of residual leaflet tethering at 1-year FU. RESULTS: A total of 94 patients (69.1% male) with a mean age of 65.1±9.7 years met the inclusion criteria. Advanced LV dysfunction (mean left ventricular ejection fraction 36.4±10.5%) and severe LV dilatation (mean left ventricular end-diastolic diameter 61.0±9.3 mm) resulted in severe mitral leaflet tethering (mean tenting height 10.6±3.0 mm) and an elevated mean EURO Score II of 4.8±4.6 prior to surgery. Subannular repair was successfully performed in all patients, without operative mortality or complications. One-year survival was 95.5%. At 12 months, a durable reduction of mitral leaflet tethering resulted in a low rate (4.2%) of recurrent MR >2+. In addition to a significant improvement in New York Heart Association (NYHA) class (22.4% patients in NYHA III/IV vs 64.5% patients at baseline, p<0.001), freedom from MACCE was observed in 91.1% of patients. CONCLUSIONS: Our study demonstrates the safety and feasibility of standardised subannular repair to treat ventricular SMR (Carpentier type IIIb) in a multicentre setting. By addressing mitral leaflet tethering, papillary muscle relocation results in very satisfactory 1-year outcomes and has the potential to durably restore MV geometry; nevertheless, long-term FU is mandatory. TRIAL REGISTRATION NUMBER: NCT03470155.

Leukocyte telomere length and mitochondrial DNA copy number associate with endothelial function in aging-related cardiovascular disease.

Background: We investigated the association between leukocyte telomere length, mitochondrial DNA copy number, and endothelial function in patients with aging-related cardiovascular disease (CVD). Methods: In total 430 patients with CVD and healthy persons were enrolled in the current study. Peripheral blood was drawn by routine venipuncture procedure. Plasma and peripheral blood mononuclear cells (PBMCs) were collected. Cell-free genomic DNA (cfDNA) and leukocytic genomic DNA (leuDNA) were extracted from plasma and PBMCs, respectively. Relative telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) were analyzed using quantitative polymerase chain reaction. Endothelial function was evaluated by measuring flow-mediated dilation (FMD). The correlation between TL of cfDNA (cf-TL), mtDNA-CN of cfDNA (cf-mtDNA), TL of leuDNA (leu-TL), mtDNA-CN of leuDNA (leu-mtDNA), age, and FMD were analyzed based on Spearman's rank correlation. The association between cf-TL, cf-mtDNA, leu-TL, leu-mtDNA, age, gender, and FMD were explored using multiple linear regression analysis. Results: cf-TL positively correlated with cf-mtDNA (r = 0.1834, P = 0.0273), and leu-TL positively correlated with leu-mtDNA (r = 0.1244, P = 0.0109). In addition, both leu-TL (r = 0.1489, P = 0.0022) and leu-mtDNA (r = 0.1929, P < 0.0001) positively correlated with FMD. In a multiple linear regression analysis model, both leu-TL (ß = 0.229, P = 0.002) and leu-mtDNA (ß = 0.198, P = 0.008) were positively associated with FMD. In contrast, age was inversely associated with FMD (ß = -0.426, P < 0.0001). Conclusion: TL positively correlates mtDNA-CN in both cfDNA and leuDNA. leu-TL and leu-mtDNA can be regarded as novel biomarkers of endothelial dysfunction.

An analysis of DPV and DIVE registry patients with chronic kidney disease according to the finerenone phase III clinical trial selection criteria.

BACKGROUND: The FIDELIO-DKD and FIGARO-DKD randomized clinical trials (RCTs) showed finerenone, a novel non-steroidal mineralocorticoid receptor antagonist (MRA), reduced the risk of renal and cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Using RCT inclusion and exclusion criteria, we analyzed the RCT coverage for patients with T2DM and CKD in routine clinical practice in Germany. METHODS: German patients from the DPV/DIVE registries who were ≥ 18 years, had T2DM and CKD (an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 OR eGFR ≥ 60 mL/min/1.73m2 and albuminuria [≥ 30 mg/g]) were included. RCT inclusion and exclusion criteria were then applied, and the characteristics of the two populations compared. RESULTS: Overall, 65,168 patients with T2DM and CKD were identified from DPV/DIVE. Key findings were (1) Registry patients with CKD were older, less often male, and had a lower eGFR, but more were normoalbuminuric vs the RCTs. Cardiovascular disease burden was higher in the RCTs; diabetic neuropathy, lipid metabolism disorders, and peripheral arterial disease were more frequent in the registry. CKD-specific drugs (e.g., angiotensin-converting enzyme inhibitors [ACEi] and angiotensin receptor blocker [ARBs]) were used less often in clinical practice; (2) Due to the RCT's albuminuric G1/2 to G4 CKD focus, they did not cover 28,147 (43.2%) normoalbuminuric registry patients, 4,519 (6.9%) albuminuric patients with eGFR < 25, and 6,565 (10.1%) patients with microalbuminuria but normal GFR (≥ 90 ml/min); 3) As RCTs required baseline ACEi or ARB treatment, the number of comparable registry patients was reduced to 28,359. Of these, only 12,322 (43.5%) registry patients fulfilled all trial inclusion and exclusion criteria. Registry patients that would have been eligible for the RCTs were more often male, had higher eGFR values, higher rates of albuminuria, more received metformin, and more SGLT-2 inhibitors than patients that would not be eligible. CONCLUSIONS: Certain patient subgroups, especially non-albuminuric CKD-patients, were not included in the RCTs. Although recommended by guidelines, there was an undertreatment of CKD-patients with renin-angiotensin system (RAS) blockers. Further research into patients with normoalbuminuric CKD and a wider prescription of RAS blocking agents for CKD patients in clinical practice appears warranted.

Autophagy-related genes analysis reveals potential biomarkers for prediction of the impaired walking capacity of peripheral arterial disease.

BACKGROUND: The role of autophagy and autophagy-related genes in peripheral arterial disease (PAD) remains unknown and may be of diagnostic and prognostic value. The aim of this study is to investigate the relationship between autophagy and PAD, and identify potential diagnostic or prognostic biomarkers for medical practice. METHODS: Differentially expressed autophagy-related genes in PAD were explored from GSE57691 and validated in our WalkByLab registry participants by quantitative real-time polymerase chain reaction (qRT-PCR). The level of autophagy in peripheral blood mononuclear cells (PBMCs) of WalkByLab participants was assessed by analyzing autophagic marker proteins (beclin-1, P62, LC3B). Single sample gene set enrichment analysis (ssGSEA) was used to evaluate the immune microenvironment within the artery wall of PAD patients and healthy persons. Chemokine antibody array and enzyme-linked immunosorbent assay were used to assess the chemokines in participants' plasma. Treadmill testing with Gardner protocol was used to evaluate participants' walking capacity. Pain-free walking distance, maximum walking distance, and walking time were recorded. Finally, a nomogram model based on logistic regression was built to predict impaired walking performance. RESULTS: A total of 20 relevant autophagy-related genes were identified, and these genes were confirmed to be expressed at low levels in our PAD participants. Western blotting demonstrated that the expression of autophagic marker proteins beclin-1 and LC3BII were significantly reduced in PAD patients' PBMCs. ssGSEA revealed that most of the autophagy-related genes were strongly correlated with immune function, with the largest number of associated genes showing interaction between cytokine-and-cytokine receptors (CCR). In this context, the chemokines growth-related oncogene (GRO) and neutrophil activating protein2 (NAP2) are highly expressed in the plasma of WalkByLab PAD patients and were significantly negatively correlated with the walking distance assessed by Gardner treadmill testing. Finally, the plasma NAP2 level (AUC: 0.743) and derived nomogram model (AUC: 0.860) has a strong predictive potential to identify a poor walking capacity. CONCLUSIONS: Overall, these data highlight both the important role of autophagy and autophagy-related genes in PAD and link them to vascular inflammation (expression of chemokines). In particular, chemokine NAP2 emerged as a novel biomarker that can be used to predict the impaired walking capacity in PAD patients.

Identification of predictive factors of diabetic ketoacidosis in type 1 diabetes using a subgroup discovery algorithm.

AIM: To identify predictive factors for diabetic ketoacidosis (DKA) by retrospective analysis of registry data and the use of a subgroup discovery algorithm. MATERIALS AND METHODS: Data from adults and children with type 1 diabetes and more than two diabetes-related visits were analysed from the Diabetes Prospective Follow-up Registry. Q-Finder, a supervised non-parametric proprietary subgroup discovery algorithm, was used to identify subgroups with clinical characteristics associated with increased DKA risk. DKA was defined as pH less than 7.3 during a hospitalization event. RESULTS: Data for 108 223 adults and children, of whom 5609 (5.2%) had DKA, were studied. Q-Finder analysis identified 11 profiles associated with an increased risk of DKA: low body mass index standard deviation score; DKA at diagnosis; age 6-10 years; age 11-15 years; an HbA1c of 8.87% or higher (≥ 73 mmol/mol); no fast-acting insulin intake; age younger than 15 years and not using a continuous glucose monitoring system; physician diagnosis of nephrotic kidney disease; severe hypoglycaemia; hypoglycaemic coma; and autoimmune thyroiditis. Risk of DKA increased with the number of risk profiles matching patients' characteristics. CONCLUSIONS: Q-Finder confirmed common risk profiles identified by conventional statistical methods and allowed the generation of new profiles that may help predict patients with type 1 diabetes who are at a greater risk of experiencing DKA.

Modeling unmeasured baseline information in observational time-to-event data subject to delayed study entry.

Unmeasured baseline information in left-truncated data situations frequently occurs in observational time-to-event analyses. For instance, a typical timescale in trials of antidiabetic treatment is "time since treatment initiation", but individuals may have initiated treatment before the start of longitudinal data collection. When the focus is on baseline effects, one widespread approach is to fit a Cox proportional hazards model incorporating the measurements at delayed study entry. This has been criticized because of the potential time dependency of covariates. We tackle this problem by using a Bayesian joint model that combines a mixed-effects model for the longitudinal trajectory with a proportional hazards model for the event of interest incorporating the baseline covariate, possibly unmeasured in the presence of left truncation. The novelty is that our procedure is not used to account for non-continuously monitored longitudinal covariates in right-censored time-to-event studies, but to utilize these trajectories to make inferences about missing baseline measurements in left-truncated data. Simulating times-to-event depending on baseline covariates we also compared our proposal to a simpler two-stage approach which performed favorably. Our approach is illustrated by investigating the impact of baseline blood glucose levels on antidiabetic treatment failure using data from a German diabetes register.

Modifiable risk factors for permanent pacemaker after transcatheter aortic valve implantation: CONDUCT registry.

OBJECTIVE: The onset of new conduction abnormalities requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) is still a relevant adverse event. The main objective of this registry was to identify modifiable procedural risk factors for an improved outcome (lower rate of PPI) after TAVI in patients at high risk of PPI. METHODS: Patients from four European centres receiving a balloon-expandable TAVI (Edwards SAPIEN 3/3 Ultra) and considered at high risk of PPI (pre-existing conduction disturbance, heavily calcified left ventricular outflow tract or short membranous septum) were prospectively enrolled into registry. RESULTS: A total of 300 patients were included: 42 (14.0%) required PPI after TAVI and 258 (86.0%) did not. Patients with PPI had a longer intensive care unit plus intermediate care stay (65.7 vs 16.3 hours, p<0.001), general ward care stay (6.9 vs 5.3 days, p=0.004) and later discharge (8.6 vs 5.0 days, p<0.001). Of the baseline variables, only pre-existing right bundle branch block at baseline (OR 6.8, 95% CI 2.5 to 18.1) was significantly associated with PPI in the multivariable analysis. Among procedure-related variables, oversizing had the highest impact on the rate of PPI: higher than manufacturer-recommended sizing, mean area oversizing as well as the use of the 29 mm valve (OR 3.4, 95% CI 1.4 to 8.5, p=0.008) all were significantly associated with PPI. Rates were higher with the SAPIEN 3 (16.1%) vs SAPIEN 3 Ultra (8.5%), although not statistically significant but potentially associated with valve sizing. Implantation depth and postdelivery balloon dilatation also tended to affect PPI rates but without a statistical significance. CONCLUSION: Valve oversizing is a strong procedure-related risk factor for PPI following TAVI. The clinical impact of the valve type (SAPIEN 3), implantation depth, and postdelivery balloon dilatation did not reach significance and may reflect already refined procedures in the participating centres, giving attention to these avoidable risk factors. TRIAL REGISTRATION NUMBER: NCT03497611.

The Frozen Elephant Technique Using a Novel Hybrid Prosthesis for Extensive Aortic Arch Disease: A Multicentre Study.

INTRODUCTION: The frozen elephant trunk technique (FET) has become routine for aortic arch and descending aortic repair. New hybrid prosthesis models are constantly being developed to increase effectiveness and durability of aortic repair. Recently, concerns were raised regarding increased post-operative bleeding using a new-generation hybrid prosthesis (E-vita® OPEN NEO, CryoLife Inc. JOTEC GmbH, Hechingen, Germany). We report the outcomes of a multi-centre experience of using the E-vita OPEN NEO. METHODS: All patients undergoing aortic surgery at five European centres using the E-vita OPEN NEO from 2020 to 2022 were included (n = 22). The primary endpoint was the amount of chest drain fluid after 24 h and re-thoracotomy rate for bleeding. RESULTS: Median patient age was 62.5 ± 12.6 years, 50.0% (11/22 patients) were female and 27.3% (6/22) of procedures were re-operative cardiac surgeries. Aortic dissection was present in 54.5% (12/22). The median cardiopulmonary bypass time was 148 min and ischaemia time was 84 min. Mortality at 30 days was 4.5% (1/22) and the stroke rate was 18.2% (4/22). The rate of re-thoracotomy for bleeding was 4.5% (1/22) with a median amount of chest drain fluid within 24 h of 569 (IQR 338-910) ml. There were no device-associated adverse events. CONCLUSIONS: Use of this new-generation hybrid prosthesis for FET was safe and effective. Patient follow-up was largely uneventful given the extent of the procedures performed. In particular, bleeding events were uncommon in this cohort of patients comprising many aortic dissections and re-operative procedures. No increase in oozing was observed.

Severe aortic stenosis management in heart valve centres compared with primary/secondary care centres.

OBJECTIVE: Current guidelines recommend use of heart valve centres (HVCs) to deliver optimal quality of care for patients with valve disease but there is no evidence to support this. The hypothesis of this study is that patient care with severe aortic stenosis (AS) will differ in HVCs compared with satellite centres. We aimed to compare the treatment of patients with AS at HVCs (tertiary care hospitals with full access to AS interventions) to satellites (hospitals without such access). METHODS: IMPULSE enhanced is a European, observational, prospective registry enrolling consecutive patients with newly diagnosed severe AS at four HVCs and 10 satellites. Clinical characteristics, interventions performed and outcomes up to 1 year by site-type were examined. RESULTS: Among 790 patients, 594 were recruited in HVCs and 196 in satellites. At baseline, patients in HVCs had more severe valve disease (higher peak aortic velocity (4.3 vs 4.1 m/s; p=0.008)) and greater comorbidity (coronary artery disease (CAD) (44% vs 27%; p<0.001) prior myocardial infarction (MI) (11% vs 5.1%; p=0.011) and chronic pulmonary disease (17% vs 8.9%; p=0.007)) than those presenting in satellites. An aortic valve replacement was performed more often by month 3 in HVCs than satellites in the overall population (52.6% of vs 31.3%; p<0.001) and in symptomatic patients (66.7% vs 43.2%, p<0.001). One-year survival rate was higher for patients in HVCs than satellites (HR2.19; 95% CI 1.28 to 3.73 total population and 2.89 (95%CI 1.64 to 5.11) for symptomatic patients. CONCLUSIONS: Our data support the implementation of referral pathways that direct patients to HVCs performing both surgery and transcatheter interventions. TRIAL REGISTRATION NUMBER: NCT03112629.

[Thrombotic thrombocytopenic purpura-a differential diagnostic challenge in an emergency]. / Thrombotisch-thrombozytopenische Purpura ­ eine differenzialdiagnostische Herausforderung im Notfall.

Thrombotic thrombocytopenic purpura (TTP), which comprises thrombocytopenia, elevated lactate dehydrogenase levels, and anemia in the combination of organ involvement, is a rare but life-threatening condition associated with an extremely high lethality in the acute phase if left untreated. Using the example of a 49-year-old woman admitted to the hospital with unexplained abdominal symptoms and subfebrile temperatures, recommendations for the emergency situation are presented. Increased awareness of the disease and targeted further diagnostics with determination of the PLASMIC score or ADAMTS13 activity may lead directly to diagnosis of TTP; delayed diagnosis is usually associated with secondary complications.