Mitral Valve Transcatheter Edge-to-Edge Repair: 1-Year Outcomes From the MiCLASP Study.

BACKGROUND: Mitral transcatheter edge-to-edge repair (M-TEER) is a guideline-recommended treatment option for patients with severe symptomatic mitral regurgitation (MR). Outcomes with the PASCAL system in a post-market setting have not been established. OBJECTIVES: The authors report 30-day and 1-year outcomes from the MiCLASP (Transcatheter Repair of Mitral Regurgitation with Edwards PASCAL Transcatheter Valve Repair System) European post-market clinical follow-up study. METHODS: Patients with symptomatic, clinically significant MR were prospectively enrolled. The primary safety endpoint was clinical events committee-adjudicated 30-day composite major adverse event rate and the primary effectiveness endpoint was echocardiographic core laboratory-assessed MR severity at discharge compared with baseline. Clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year. RESULTS: A total of 544 patients were enrolled (59% functional MR, 30% degenerative MR). The 30-day composite major adverse event rate was 6.8%. MR reduction was significant from baseline to discharge and sustained at 1 year with 98% of patients achieving MR ≤2+ and 82.6% MR ≤1+ (all P < 0.001 vs baseline). One-year Kaplan-Meier estimate for survival was 87.3%, and freedom from heart failure hospitalization was 84.3%. Significant functional and quality-of-life improvements were observed at 1 year, including 71.6% in NYHA functional class I/II, 14.4-point increase in Kansas City Cardiomyopathy Questionnaire score, and 24.2-m improvement in 6-minute walk distance (all P < 0.001 vs baseline). CONCLUSIONS: One-year outcomes of this large cohort from the MiCLASP study demonstrate continued safety and effectiveness of M-TEER with the PASCAL system in a post-market setting. Results demonstrate high survival and freedom from heart failure hospitalization, significant and sustained MR reduction, and improvements in symptoms, functional capacity, and quality of life.

Lactate as a Predictor of 30-Day Mortality in Cardiogenic Shock.

Background/Objectives: This study sought to evaluate the efficacy of various lactate measurements within the first 24 h post-intensive care unit (ICU) admission for predicting 30-day mortality in cardiogenic shock patients. It compared initial lactate levels, 24 h levels, peak levels, and 24 h clearance, alongside the Simplified Acute Physiology Score 3 (SAPS3) score, to enhance early treatment decision-making. Methods: A retrospective analysis of 64 patients assessed the prognostic performance of lactate levels and SAPS3 scores using logistic regression and AUROC calculations. Results: Of the baseline parameters, only the SAPS3 score predicted survival independently. The lactate level after 24 h (LL) was the most accurate predictor of mortality, outperforming initial levels, peak levels, and 24 h-clearance, and showing a significant AUROC. LL greater than 3.1 mmol/L accurately predicted mortality with high specificity and moderate sensitivity. Conclusions: Among lactate measurements for predicting 30-day mortality in cardiogenic shock, the 24 h lactate level was the most effective one, suggesting its superiority for early prognostication over initial or peak levels and lactate clearance.

Diagnosis and prognosis of abnormal cardiac scintigraphy uptake suggestive of cardiac amyloidosis using artificial intelligence: a retrospective, international, multicentre, cross-tracer development and validation study.

BACKGROUND: The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners. METHODS: In this retrospective, international, multicentre, cross-tracer development and validation study, 16 241 patients with 19 401 scans were included from nine centres: one hospital in Austria (consecutive recruitment Jan 4, 2010, to Aug 19, 2020), five hospital sites in London, UK (consecutive recruitment Oct 1, 2014, to Sept 29, 2022), two centres in China (selected scans from Jan 1, 2021, to Oct 31, 2022), and one centre in Italy (selected scans from Jan 1, 2011, to May 23, 2023). The dataset included all patients referred to whole-body 99mTc-scintigraphy with an anterior view and all 99mTc-labelled tracers currently used to identify cardiac amyloidosis-suggestive uptake. Exclusion criteria were image acquisition at less than 2 h (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-hydroxymethylene diphosphonate, and 99mTc-methylene diphosphonate) or less than 1 h (99mTc-pyrophosphate) after tracer injection and if patients' imaging and clinical data could not be linked. Ground truth annotation was derived from centralised core-lab consensus reading of at least three independent experts (CN, TT-W, and JN). An AI system for detection of cardiac amyloidosis-associated high-grade cardiac tracer uptake was developed using data from one centre (Austria) and independently validated in the remaining centres. A multicase, multireader study and a medical algorithmic audit were conducted to assess clinician performance compared with AI and to evaluate and correct failure modes. The system's prognostic value in predicting mortality was tested in the consecutively recruited cohorts using cox proportional hazards models for each cohort individually and for the combined cohorts. FINDINGS: The prevalence of cases positive for cardiac amyloidosis-suggestive uptake was 142 (2%) of 9176 patients in the Austrian, 125 (2%) of 6763 patients in the UK, 63 (62%) of 102 patients in the Chinese, and 103 (52%) of 200 patients in the Italian cohorts. In the Austrian cohort, cross-validation performance showed an area under the curve (AUC) of 1·000 (95% CI 1·000-1·000). Independent validation yielded AUCs of 0·997 (0·993-0·999) for the UK, 0·925 (0·871-0·971) for the Chinese, and 1·000 (0·999-1·000) for the Italian cohorts. In the multicase multireader study, five physicians disagreed in 22 (11%) of 200 cases (Fleiss' kappa 0·89), with a mean AUC of 0·946 (95% CI 0·924-0·967), which was inferior to AI (AUC 0·997 [0·991-1·000], p=0·0040). The medical algorithmic audit demonstrated the system's robustness across demographic factors, tracers, scanners, and centres. The AI's predictions were independently prognostic for overall mortality (adjusted hazard ratio 1·44 [95% CI 1·19-1·74], p<0·0001). INTERPRETATION: AI-based screening of cardiac amyloidosis-suggestive uptake in patients undergoing scintigraphy was reliable, eliminated inter-rater variability, and portended prognostic value, with potential implications for identification, referral, and management pathways. FUNDING: Pfizer.

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.

Reduced Monocyte and Neutrophil Infiltration and Activation by P-Selectin/CD62P Inhibition Enhances Thrombus Resolution in Mice.

BACKGROUND: Venous thromboembolism is a major health problem. After thrombus formation, its resolution is essential to re-establish blood flow, which is crucially mediated by infiltrating neutrophils and monocytes in concert with activated platelets and endothelial cells. Thus, we aimed to modulate leukocyte function during thrombus resolution post-thrombus formation by blocking P-selectin/CD62P-mediated cell interactions. METHODS: Thrombosis was induced by inferior vena cava stenosis through ligation in mice. After 1 day, a P-selectin-blocking antibody or isotype control was administered and thrombus composition and resolution were analyzed. RESULTS: Localizing neutrophils and macrophages in thrombotic lesions of wild-type mice revealed that these cells enter the thrombus and vessel wall from the caudal end. Neutrophils were predominantly present 1 day and monocytes/macrophages 3 days after vessel ligation. Blocking P-selectin reduced circulating platelet-neutrophil and platelet-Ly6Chigh monocyte aggregates near the thrombus, and diminished neutrophils and Ly6Chigh macrophages in the cranial thrombus part compared with isotype-treated controls. Depletion of neutrophils 1 day after thrombus initiation did not phenocopy P-selectin inhibition but led to larger thrombi compared with untreated controls. In vitro, P-selectin enhanced human leukocyte function as P-selectin-coated beads increased reactive oxygen species production by neutrophils and tissue factor expression of classical monocytes. Accordingly, P-selectin inhibition reduced oxidative burst in the thrombus and tissue factor expression in the adjacent vessel wall. Moreover, blocking P-selectin reduced thrombus density determined by scanning electron microscopy and increased urokinase-type plasminogen activator levels in the thrombus, which accelerated caudal fibrin degradation from day 3 to day 14. This accelerated thrombus resolution as thrombus volume declined more rapidly after blocking P-selectin. CONCLUSIONS: Inhibition of P-selectin-dependent activation of monocytes and neutrophils accelerates venous thrombosis resolution due to reduced infiltration and activation of innate immune cells at the site of thrombus formation, which prevents early thrombus stabilization and facilitates fibrinolysis.

Impact of the COVID-19 Pandemic on Global TAVR Activity: The COVID-TAVI Study.

BACKGROUND: The COVID-19 pandemic adversely affected health care systems. Patients in need of transcatheter aortic valve replacement (TAVR) are especially susceptible to treatment delays. OBJECTIVES: This study sought to evaluate the impact of the COVID-19 pandemic on global TAVR activity. METHODS: This international registry reported monthly TAVR case volume in participating institutions prior to and during the COVID-19 pandemic (January 2018 to December 2021). Hospital-level information on public vs private, urban vs rural, and TAVR volume was collected, as was country-level information on socioeconomic status, COVID-19 incidence, and governmental public health responses. RESULTS: We included 130 centers from 61 countries, including 65,980 TAVR procedures. The first and second pandemic waves were associated with a significant reduction of 15% (P < 0.001) and 7% (P < 0.001) in monthly TAVR case volume, respectively, compared with the prepandemic period. The third pandemic wave was not associated with reduced TAVR activity. A greater reduction in TAVR activity was observed in Africa (-52%; P = 0.001), Central-South America (-33%; P < 0.001), and Asia (-29%; P < 0.001). Private hospitals (P = 0.005), urban areas (P = 0.011), low-volume centers (P = 0.002), countries with lower development (P < 0.001) and economic status (P < 0.001), higher COVID-19 incidence (P < 0.001), and more stringent public health restrictions (P < 0.001) experienced a greater reduction in TAVR activity. CONCLUSIONS: TAVR procedural volume declined substantially during the first and second waves of the COVID-19 pandemic, especially in Africa, Central-South America, and Asia. National socioeconomic status, COVID-19 incidence, and public health responses were associated with treatment delays. This information should inform public health policy in case of future global health crises.

Mixed aortic valve disease: Association with paravalvular leak and reduced survival after TAVR.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) revolutionized the therapy of severe aortic stenosis (AS) with rising numbers. Mixed aortic valve disease (MAVD) treated by TAVR is gaining more interest, as those patients represent a more complex cohort as compared to isolated AS. However, concerning long-term outcome for this cohort only limited data is available. AIMS: To assess the prevalence of MAVD in TAVR patients, investigate its association with paravalvular regurgitation (PVR), and analyse its impact on long-term mortality after TAVR. METHODS: We conducted a registry-based cohort study using the Vienna TAVR registry, enrolling patients who underwent TAVR at Medical University of Vienna between 01/2007 and 05/2020 with available TTE before and after TAVR (n=880). Data analysis included PVR incidence and long-term survival outcomes. RESULTS: 647 (73.52%) out of 880 patients had > mild AR next to severe AS. MAVD was associated with PVR compared to isolated AS with an OR of 2.06, 95% CI: 1.51- 2.81; p= <0.001. More than mild PVR after TAVR, (n168 out of 880 = 19.09%) was related to higher mortality compared to absence of PVR with a HR of 1.33, 95% CI: 1.05- 1.67; p= 0.016. MAVD patients developing ≥ mild PVR after TAVR was also associated with higher mortality compared to absence of PVR with HR of 1.30 and 95% CI: 1.04-1.62; p= 0.022. CONCLUSIONS AND RELEVANCE: MAVD is prevalent among TAVR patients and presents unique challenges, with increased PVR risk and worse outcomes compared to isolated AS. Long-term survival for MAVD patients, not limited to those developing PVR post TAVR is compromised. Earlier intervention before the occurrence of structural myocardial damage or surgical valve replacement might be a potential workaround to improve outcomes.

Annular Remodeling predicts Outcome in Isolated Severe Tricuspid Regurgitation: A Registry-based Echocardiographic Analysis.

AIMS: Depending on volume status, secondary tricuspid regurgitation (sTR) has a strong dynamic component. In contrast, associated structural dilatation of the tricuspid annulus and the right heart chambers may be less volume dependent. This study aimed to assess the prognostic value of right heart remodeling in isolated severe sTR (isoTR). METHODS AND RESULTS: A total of 36,000 patients from the longitudinal echocardiographic database of our tertiary center were screened for severe isoTR [vena contracta (VC)≥7mm] in the absence of atrial fibrillation (AF), other valve disease, and/or reduced systolic left ventricular function. Echocardiographic examinations were reread, focusing on right ventricular (RV) parameters and on quantitative and qualitative parameters of isoTR. All-cause mortality was defined the primary endpoint.216 patients fulfilled the inclusion criteria. Severe TR was predominant, only few were classified in the new grades massive [n=23(10%)] and torrential TR [n=4(2%)]. During a median follow-up of 35 months (20-53), all-cause mortality was 31%(n=67). Multivariate Cox regression analysis revealed no association of VC, EROA, or regurgitant volume with all-cause mortality. However, indexed RV end-diastolic diameter (p<0.001), indexed right atrial dimensions (p=0.019), and particularly tricuspid valve (TV) annulus diameter diastole index (TADI:p=0.002) and TV annulus diameter systole index (TASI:p=0.001) were significantly associated with outcome. CONCLUSION: Severe isolated TR in absence of AF is a rare finding with grim prognosis. Tricuspid annular diameter dimensions rather than quantitative measures of TR proved to be of significant prognostic value indicating a continuous remodeling leading to a "point of no return" with dismal outcome.

Decreased percentages of plasmacytoid dendritic cells predict survival in critically ill patients.

Critically ill patients admitted to intensive care units (ICUs) suffer from a broad variety of life-threatening conditions. Irrespective of the initial cause of hospitalization, many experience systemic immune dysregulation. Dendritic cells (DCs) are the most potent antigen-presenting cells and play a pivotal role in regulating the immune response by linking the innate to the adaptive immune system. The aim of this study was to analyze whether DCs or their respective subsets are associated with 30-day mortality in an unselected patient cohort admitted to a medical ICU with a cardiovascular focus. 231 patients were included in this single-center prospective observational study. Blood was drawn at admission and after 72 hours. Subsequently, flow cytometry was utilized for the analysis of DCs and their respective subsets. In the total cohort, low percentages of DCs were significantly associated with sepsis, respiratory failure, and septic shock. In particular, a significantly lower percentage of circulating plasmacytoid dendritic cells (pDCs) was found to be a strong and independent predictor of 30-day mortality after adjustment for demographic and clinical variables with an HR of 4.2 (95% CI: 1.3-13.3, p = 0.015). Additionally, low percentages of pDCs were correlated with additional markers of inflammation and organ dysfunction. In conclusion, we observed low percentages of DCs in patients admitted to an ICU suffering from sepsis, respiratory failure, and cardiogenic shock, suggesting their depletion as a contributing mechanism for the development of immune paralysis. In our cohort, pDCs were identified as the most robust subset to predict 30-day mortality.

Amyloid Burden Correlates with Electrocardiographic Findings in Patients with Cardiac Amyloidosis-Insights from Histology and Cardiac Magnetic Resonance Imaging.

Cardiac amyloidosis (CA) is associated with several distinct electrocardiographic (ECG) changes. However, the impact of amyloid depositions on ECG parameters is not well investigated. We therefore aimed to assess the correlation of amyloid burden with ECG and test the prognostic power of ECG findings on outcomes in patients with CA. Consecutive CA patients underwent ECG assessment and cardiac magnetic resonance imaging (CMR), including the quantification of extracellular volume (ECV) with T1 mapping. Moreover, seven patients underwent additional amyloid quantification using immunohistochemistry staining of endomyocardial biopsies. A total of 105 CA patients (wild-type transthyretin: 74.3%, variant transthyretin: 8.6%, light chain: 17.1%) were analyzed for this study. We detected correlations of total QRS voltage with histologically quantified amyloid burden (r = -0.780, p = 0.039) and ECV (r = -0.266, p = 0.006). In patients above the ECV median (43.9%), PR intervals were significantly longer (p = 0.016) and left anterior fascicular blocks were more prevalent (p = 0.025). In our survival analysis, neither Kaplan-Meier curves (p = 0.996) nor Cox regression analysis detected associations of QRS voltage with adverse patient outcomes (hazard ratio: 0.995, p = 0.265). The present study demonstrated that an increased amyloid burden is associated with lower voltages in CA patients. However, baseline ECG findings, including QRS voltage, were not associated with adverse outcomes.

Outcomes after TAVI in patients with atrial fibrillation and a history of recent PCI: Results from the ENVISAGE-TAVI AF trial.

BACKGROUND: Patients with atrial fibrillation (AF) and a recent (≤ 90 days) percutaneous coronary intervention (PCI) undergoing transcatheter aortic valve implantation (TAVI) are at high bleeding risk due to the addition of oral antiplatelet (OAP) agents on top of oral anticoagulants. Data on outcomes of these patients are needed to optimize antithrombotic treatment. METHODS: This analysis compared annualized clinical event rates in patients with and without a recent PCI enrolled in ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban and vitamin K antagonists in AF patients after TAVI. The primary efficacy and safety outcomes were net adverse clinical events (NACE) and major bleeding. RESULTS: Overall, 132 (94.3%) patients with a recent PCI (n = 140) received OAP after TAVI, compared with 692 (55.9%) patients without a recent PCI (n = 1237). Among patients with a recent PCI on OAP agents, use of dual antiplatelet therapy decreased to 5.5%, and use of single antiplatelet therapy (SAPT) increased to 78.0% over 3 months post-randomization. Conversely, use of SAPT predominated at all time points in patients without a recent PCI history. There were no significant differences in the incidence of NACE or other outcomes assessed, except for major bleeding events, which were more frequent in patients with vs without a recent PCI history (hazard ratio [95% confidence interval]: 2.17 [1.27, 3.73]; P = 0.005). CONCLUSIONS: Patients with AF undergoing TAVI with a recent PCI have a similar risk of ischemic events and mortality, but an increased risk of major bleeding compared with patients without a recent PCI.

ACURATE neo2 Transcatheter aortic valve implantation without balloon aortic valvuloplasty - direct ACURATE neo2.

BACKGROUND: ACURATE neo2 (Neo2) implantation is performed after systematic Balloon Aortic Valvuloplasty (BAV) in most patients. No reports exist about the feasibility and safety of direct Neo2 transcatheter aortic valve implantation (TAVI) in comparison to the standard practice. AIM: We aimed to identify the patients' baseline anatomical characteristics, procedural, and early post-procedural outcomes in patients treated using Neo2 with and without BAV. METHODOLOGY: This is a retrospective multicentre analysis of 499 patients with severe aortic stenosis who underwent TAVI using Neo2. The comparison was done according to the performance or omission of BAV. Echocardiography and computed tomography were analysed by an independent Core Lab. Propensity score matching (PSM) was performed based on the annular diameter and AV calcium volume, which identified 84 matched pairs. RESULTS: Among the cohort included, 391 (78%) patients received BAV (BAV-yes) and 108 (22%) were not attempted (BAV-no or Direct TAVI). Patients in BAV-no cohort had smaller annular diameter (22.6 vs 23.4 mm; p < 0.001) and lower calcium volume (163 vs 581 mm3; p < 0.001) compared to BAV-yes cohort. In the matched cohort, VARC-3 device technical success was similar (95%) and all other outcome measures were statistically comparable between cohorts. CONCLUSION: Direct TAVI using ACURATEneo2 without pre-TAVI balloon aortic valvuloplasty in patients with mild or less valve calcifications might be feasible and associated with comparable early outcomes compared to patients with similar anatomical features undergoing systematic balloon valvuloplasty.

Association of Periprocedural Inflammatory Activation With Increased Risk for Early Coronary Stent Thrombosis.

BACKGROUND: Stent thrombosis is a rare but deleterious event. Routine coronary angiography with percutaneous coronary intervention (PCI) is often deferred in the presence of laboratory markers of acute inflammation to prevent complications. The aim of this study was to investigate whether an acute inflammatory state is associated with an increased risk of early stent thrombosis. METHODS AND RESULTS: Within a prospective single-center registry, the association between preprocedural acute inflammatory activation, defined as C-reactive protein plasma levels >50 mg/L or a leukocyte count >12 g/L, and occurrence of early (≤30 days) stent thrombosis was evaluated. In total, 11 327 patients underwent PCI and of those, 6880 patients had laboratory results available. 49.6% of the study population received PCI for an acute coronary syndrome and 50.4% for stable ischemic heart disease. In patients with signs of acute inflammatory activation (24.9%), PCI was associated with a significantly increased risk for stent thrombosis (hazard ratio, 2.89; P<0.00001), independent of age, sex, kidney function, number and type of stents, presence of multivessel disease, choice of P2Y12 inhibitor, and clinical presentation. Elevated laboratory markers of acute inflammation were associated with the occurrence of stent thrombosis in both patients with acute coronary syndrome (hazard ratio, 2.63; P<0.001) and in patients with stable ischemic heart disease (hazard ratio, 3.57; P<0.001). CONCLUSIONS: An acute inflammatory state at the time of PCI was associated with a significantly increased risk of early stent thrombosis. Evidence of acute inflammation should result in deferred PCI in elective patients, while future studies are needed for patients with acute coronary syndrome.

Tricuspid edge-to-edge repair for tricuspid valve prolapse and flail leaflet: feasibility in comparison to patients with secondary tricuspid regurgitation.

AIMS: Transcatheter tricuspid edge-to-edge repair (T-TEER) has gained widespread use for the treatment of tricuspid regurgitation (TR) in symptomatic patients with high operative risk. Although secondary TR is the most common pathology, some patients exhibit primary or predominantly primary TR. Characterization of patients with these pathologies in the T-TEER context has not been systematically performed. METHODS AND RESULTS: Patients assigned to T-TEER by the interdisciplinary heart team were consecutively recruited in two European centres over 4 years. Echocardiographic images were evaluated to distinguish between primary and secondary causes of TR. Both groups were compared concerning procedural results. A total of 339 patients were recruited, 13% with primary TR and 87% with secondary TR. Patients with primary TR had a smaller right ventricle (basal diameter 45 vs. 49 mm, P = 0.004), a better right ventricular function (fractional area change 45 vs. 41%, P = 0.001), a smaller right (28 vs. 34 cm2, P = 0.021) and left (52 vs. 67 mL/m2, P = 0.038) atrium, and a better left ventricular ejection fraction (60 vs. 52%, P = 0.005). The severity of TR was similar in primary and secondary TR at baseline (TR vena contracta width pre-interventional 13 ± 4 vs. 14 ± 5 mm, P = 0.19), and T-TEER significantly reduced TR in both groups (TR vena contracta width post-interventional 4 ± 3 vs. 5 ± 5 mm, P = 0.10). These findings remained stable after propensity score matching. Complications were similar between both groups. CONCLUSION: T-TEER confers equally safe and effective reduction of TR in patients with primary and secondary TR.

[Management of cardiomyopathies : New ESC guidelines 2023]. / Management von Kardiomyopathien : Neue ESC-Leitlinie 2023.

The group of cardiomyopathies has received increasing attention over the last few years after some of the causes were identified and they could be characterized more exactly using modern imaging methods. New definitions and classification schemes were regularly provided by national and international cardiac societies. The new guidelines of the European Society of Cardiology (ESC) from 2023 on the management of cardiomyopathies are the first guidelines that comprehensively address all cardiomyopathies in one document. As these are new guidelines most of the recommendations are also new. An exception is the section on hypertrophic cardiomyopathy (HCM), which provides a targeted update of the 2014 ESC guidelines on the diagnosis and treatment of HCM. The main aim of the guidelines is to provide clear guidance for the diagnosis of cardiomyopathies, to highlight general assessment and management problems and to point out the relevant scientific evidence for the recommendations to the readership. Due to the magnitude detailed descriptions and recommendations cannot be provided for each individual cardiomyopathy phenotype; however, reference is made to the relevant literature.

[Androgen deprivation therapy and cardiovascular morbidity in prostate cancer: a narrative review]. / Androgendeprivationstherapie und kardiovaskuläre Morbidität beim Prostatakarzinom: ein narratives Review.

Prostate cancer is the most common malignancy in men, mostly affecting older men who harbor an increased prevalence of cardiovascular disease and metabolic syndrome. Androgen deprivation therapy (ADT), the standard therapy for various stages of prostate cancer, further increases the risk for cardiovascular disease and for metabolic syndrome. Therefore, screening for cardiovascular risk factors should be performed prior to the initiation of ADT, and, if necessary, cardiological evaluation and interdisciplinary management should be provided during and after completion of ADT. Moreover, the use of a gonadotropin-releasing hormone (GnRH) antagonist may help reduce cardiovascular risk in patients with cardiovascular disease.

Reduction in 99mTc-DPD myocardial uptake with therapy of ATTR cardiomyopathy.

Aims: Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis.Methods and results: ATTRv-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0-12.0) of treatment with RNAi therapeutics (patisiran: n = 5, inotersen: n = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, p = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, p < .001) in ATTRwt-CM patients (historical control cohort: n = 40) at follow-up [9.0 months (IQR: 7.0-10.0)] without beneficial impact on cardiac function.Conclusions: RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial 99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.

Neutrophil extracellular traps induce persistent lung tissue damage via thromboinflammation without altering virus resolution in a mouse coronavirus model.

BACKGROUND: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells, and are highly procoagulant. Anticoagulation treatment was shown to reduce in-hospital mortality, indicating thromboinflammatory complications. However, data are sparsely available on the involvement of NETs in secondary events after virus clearance, which can lead to persistent lung damage and postacute sequelae with chronic fatigue and dyspnea. OBJECTIVES: This study focuses on late-phase events using a murine model of viral lung infection with postacute sequelae after virus resolution. METHODS: C57BL/6JRj mice were infected intranasally with the betacoronavirus murine coronavirus (MCoV, strain MHV-A95), and tissue samples were collected after 2, 4, and 10 days. For NET modulation, mice were pretreated with OM-85 or GSK484 and DNase I were administered intraperitoneally between days 2 to 5 and days 4 to 7, respectively. RESULTS: Rapid, platelet-attributed thrombus formation was followed by a second, late phase of thromboinflammation. This phase was characterized by negligible virus titers but pronounced tissue damage, apoptosis, oxidative DNA damage, and presence of NETs. Inhibition of NETs during the acute phase did not impact virus burden but decreased lung cell apoptosis by 67% and oxidative stress by 94%. Prevention of neutrophil activation by immune training before virus infection reduced damage by 75%, NETs by 31%, and pulmonary thrombi by 93%. CONCLUSION: NETs are detrimental inducers of tissue damage during respiratory virus infection but do not contribute to virus clearance.

Impact of stroke history on procedural cerebrovascular insult probability and long-term outcome after TAVI.

BACKGROUND: In TAVI procedural stroke is one of the most feared complications and for this reason also extensively studied. But there is a lack of data concerning the impact of previous stroke on procedural stroke and on long-term survival. The aim of this registry-based cohort study is to evaluate the prevalence of previous stroke in TAVI patients and its impact on procedural stroke risk as well as long-term outcome. METHODS: We included all patients treated with TAVI between January 2007 and December 2020 and investigated concerning previous stroke in their medical history. Among 958 patients, 55 patients had previous stroke and were included in the present analysis. RESULTS: The salient finding of the present study is that previous stroke is significantly associated with higher all-cause mortality and has established itself as a predictor for poor outcome after TAVI. This is also observed after adjusting for confounders like EuroSCORE II (European system for cardiac operative risk evaluation) and AF (atrial fibrillation) as one of the main underlying diseases for cerebrovascular insult (CVI). However, previous stroke is not associated with higher rates of procedural CVI. CONCLUSION: A history of stroke is significantly associated with higher all-cause mortality and has established itself as a predictor for poor outcome after TAVI without higher rates of procedural stroke.

In-hospital Outcomes of Rotational Atherectomy in ST-Elevation Myocardial Infarction: Results From the Multicentre ROTA-STEMI Network.

BACKGROUND: Although the use of rotational atherectomy (RA) is off-label in the setting of ST-elevation myocardial infarction (STEMI), it can be the only option in severely calcified culprit lesions to achieve procedural success. We sought to investigate the safety and feasibility of RA during primary percutaneous coronary intervention (PPCI). METHODS: This was a retrospective observational study of patients who underwent RA during PPCI from 12 European centres. The main outcomes were procedural success (defined as successful stent implantation with final thrombolysis in myocardial infarction [TIMI] flow 3 and residual stenosis < 30%) and in-hospital mortality. A comparison of patients presenting with and without shock was performed. RESULTS: In 104 patients with RA during STEMI, the mean age was 72.8 ± 9.1 years, and 35% presented with cardiogenic shock. Bailout RA was performed in 76.9% of cases. Mean burr size was 1.42 ± 0.21 mm. Procedural success was achieved in 86.5% of cases, with no difference between shocked and nonshocked patients (94.4% vs 82.4%; P = 0.13). In-hospital stent thrombosis occurred in 0.96%, perforation in 1.9% and burr entrapment in 2.9% of cases. In spite of equally high procedural success, in-hospital mortality was higher in shocked (50%) compared with nonshocked patients (1.5%; P < 0.0001). CONCLUSIONS: Patients presenting with STEMI requiring RA, represent a high-risk population, frequently presenting with cardiogenic shock. In this analysis of selected patients, RA was performed as a bailout strategy in the majority, and, as such, RA seems to be feasible with a high procedural success rate. In the absence of cardiogenic shock, RA-facilitated PCI seems to be associated with low in-hospital mortality.