Henrik Bjursten

Cystatin C was identified as a marker of glomerular filtration rate (GFR) in 1979, and the parallel analysis of cystatin C and creatinine led to the identification of shrunken pore syndrome (SPS) - a new kidney disorder - in 2015. Since then, it has been shown that cystatin C in many aspects is superior to creatinine as a marker of GFR and cardiovascular risk. SPS, an entity within the selective glomerular hypofiltration syndromes (SGHS), has been demonstrated to be associated with a strong increase in morbidity and mortality in several populations. Despite the seriousness of SPS and SGHS, and the availability of potential treatments, many patients with these conditions remain undiagnosed, due to the limitations of the international Kidney Disease Improving Global Outcomes Organization (KDIGO) guidelines. Given the significant clinical advantages of cystatin C in diagnosing and treating kidney disorders, there is a need to expand the KDIGO guidelines to include cystatin C measurements alongside creatinine at least in the initial patient evaluation but also in follow-up evaluations. This would improve the early detection and management of patients with kidney diseases, ultimately enhancing patient outcomes. The present discourse summarizes the development of this understanding from the original observations in 1979 and 2015 to the latest findings.

Introduction: Data are lacking about the risk for death and major adverse cardiovascular events (MACE) after transcatheter aortic valve implantation (TAVI), compared to the general population. Therefore, we assessed the risk for all-cause death and MACE after TAVI in patients aged 65 years and older, in comparison to an age- and sex-matched control population. Methods and results: In total, 5924 TAVI patients and 10 928 matched controls [mean age 82.1, standard deviation (SD) 6.0, and 81.9, SD 6.1, respectively] were included from 2014 to 2020. The SWEDEHEART registry and four mandatory national registers were used to collect data. Cox regression models were used to assess the association with all-cause mortality and MACE risk. In total, 1410 (23.8%) of the TAVI patients and 2115 (19.4%) controls died during the follow-up period. Median follow-up was 1.9 years (inter quartile range 0.9–3.3) respectively. The crude mortality and MACE risks were higher in TAVI patients than in controls {hazard ratios 1.27 [95% Confidence interval (CI): 1.19–1.36] and HR 1.44 (95% CI: 1.35–1.53), respectively}. After adjustment, there was a lower risk for both mortality and MACE in TAVI patients [adjusted hazard ratio (aHR) 0.77 (95% CI: 0.71–0.84) and aHR 0.90 (95% CI: 0.83–0.98), respectively]. Conclusion: After adjustments for comorbidities, the mortality risk was lower in TAVI patients, compared with an age- and sex-matched control population. These findings suggest that the high burden of comorbidities in TAVI patients has a strong impact on the risk for mortality and MACE after TAVI.

Objective: Various percutaneous approaches are under development to perform transcatheter treatment of mitral valve disease, where many try to anchor in the left ventricle. This pilot study investigates the durability of different anchoring points and types in the left ventricle. Anchoring was tested in three different locations: the head of the papillary muscle, the lateral wall of the ventricle, and the apex of the ventricle. In addition, two different anchoring types were tested: PTFE sutures that mimicked mitral valve repair and a de novo developed 5 mm helix. Results: The lowest numerical strain/compliance during the first cycle was seen for the head of papillary muscle anchoring (both surgical and helix). Migration of strain limits over 300 cycles was seen for all locations. Numerically, the lowest migration was for the helix in the papillary muscle. PTFE in the head of the papillary muscle is standard practice in mitral valve repair and was used as a reference in the present study. The anchoring that gave the most consistent results was a helix in the papillary muscle, while other anchoring points showed larger compliance and/or migration.

Background: Transcatheter aortic valve implantation (TAVI) is an increasingly important treatment option for patients with severe aortic stenosis. Its best implementation is debated, as few centres with high volumes are associated with better outcomes, while centralization might lead to an inferior availability of treatment for patients living far away. The aim of this study was to investigate the implementation of TAVI in Sweden with a focus on regional differences in terms of availability, short-term mortality, and waiting times. Methods: All patients undergoing TAVI between 2008 and 2020 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. SWENTRY was linked to the National Cause of Death Registry and to publicly available geospatial data from Statistics Sweden. Results: A total of 7280 patients were included. Over time, TAVI interventions increased markedly, while surgical aortic valve replacement (SAVR) remained constant. There were no statistically significant regional differences in incidence between counties with or without a local TAVI centre (P = 0.7) and no clustering tendencies around regions with a local TAVI centre (P = 0.99). Thirty-day mortality improved over time without evidence of regional differences. No regional differences in waiting time from decision to intervention were found for TAVI centre regions and non-TAVI centre regions (P = 0.7). Conclusion: This nationwide study indicated no regional differences in terms of availability, short-term mortality, or waiting times. An organization with a few specialized centres was found to be sufficient to provide national coverage of TAVI interventions.

Introduction: Acute kidney injury (AKI) in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is associated with high mortality. The objective of this study was to investigate whether cytokine levels before the initiation of ECMO treatment could predict AKI. We also aimed to investigate the impact of AKI on 30-day and 1-year mortality. Methods: Serum cytokine levels were analyzed in 100 consecutive VA-ECMO-treated patients at pre-cannulation, at 48 h post-cannulation, and at 8 days. Clinical data to establish the incidence and outcome of AKI after the start of ECMO was retrieved from the local ECMO registry. Setting: The study was conducted at tertiary care, university hospital. Participants included 100 patients treated with VA-ECMO. Interventions: The blood samples for cytokine analysis were collected before VA-ECMO treatment, at 48 h after VA-ECMO treatment was started, and at 8 days. Results: Pre-cannulation serum IL-10 levels were significantly higher in patients who developed AKI (212 [38.9, 620.7]) versus those who did not (49.0 [11.9, 102.2]; p = 0.007), and the development of AKI can be predicted by pre-cannulation IL-10 levels (p = 0.025, OR = 1.2 [1.02–1.32]). The development of AKI during ECMO treatment is associated with increased 30-day mortality (p = 0.049) compared to patients who did not develop AKI and had a pre-cannulation estimated glomerular filtration rate ≥ 45 mL/min. The 1-year survival rate for patients with AKI who survived the first 30 days of ECMO treatment is comparable to that of patients without AKI. Conclusion: Increased pre-cannulation IL-10 levels are associated with the development of AKI during VA-ECMO support. AKI is associated with increased 30-day mortality compared to patients with no AKI and better renal function. However, patients with AKI who survive the first 30 days have a 1-year survival rate similar to those without AKI.

Background: ACURATE neo2 is a transcatheter aortic valve implantation system consisting of a self‐expanding bioprosthetic valve with supra‐annular leaflet position and featuring innovations to facilitate placement accuracy and reduce paravalvular regurgitation. Methods and Results: The goal of the Early neo2 (Early neo2 Registry of the ACURATE neo2 TAVI Prosthesis) was to gather real‐life data on safety and efficacy in a European transcatheter aortic valve implantation population treated with ACURATE neo2 . Data were collected from 554 consecutive patients treated with ACURATE neo2 at 12 European sites (mean age, 82 years; 66% women; mean European System for Cardiac Operative Risk Evaluation II, 4.5%±3.8%) between September 2020 and March 2021. The composite primary end point was the occurrence of any of the following: postoperative (in‐hospital) paravalvular regurgitation grade ≥2, in‐hospital acute kidney injury stage 3, postoperative pacemaker implantation, 30‐day death, and 30‐day stroke. The primary end point occurred in 12.6% of patients. The 30‐day rates for all‐cause death and all stroke were 1.3% and 2.7%, respectively, and 1.5% of patients exhibited stage 3 acute kidney injury. A total of 34 patients (6.2%) received a postoperative permanent pacemaker. Per core laboratory–adjudicated echocardiographic analysis, mean postoperative aortic valve gradient was 7.6±3.3 mm Hg, and 2.8% of patients exhibited paravalvular regurgitation grade ≥2. Conclusions: In this report of postmarket use of the ACURATE neo2 valve in a real‐world transcatheter aortic valve implantation population, patients exhibited favorable postoperative hemodynamics and clinical outcomes and a low rate of postoperative pacemaker implantation.

Henrik Bjursten, MD PhD; Response to: Fewer transfusions are still more—red blood cell transfusions affect long-term mortality in cardiac surgery, European Jour

Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)‐markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5–30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine‐based GFR‐estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor‐blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C‐based GFR‐estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.