Search

We report a new variant of the femtosecond transition-state spectroscopy technique-transient stimulated emission pumping (TSEP). The initial application of TSEP to studies of ozone visible photodissociation indicates that the molecule is trapped in the Franck–Condon region for ∼90 fs. The wave packet then spreads along the reaction coordinate. [ABSTRACT FROM AUTHOR]

Rationale: The mouse model of bleomycin-induced lung injury offers an approach to study idiopathic pulmonary fibrosis, a progressive interstitial lung disease with poor prognosis. Progenitor cell-based treatment strategies might combine antiinflammatory effects and the capacity for tissue repair. Objectives: To expand progenitor cells with reparative and regenerative capacities and to evaluate their protective effects on pulmonary fibrosis in vivo. Methods: Prominin-1/CD133(+) epithelial progenitor cells (PEPs) were expanded from adult mouse lungs after digestion and culture of distal airways. Lung fibrosis was induced in C57Bl/6 mice by instillation of bleomycin. Two hours later, animals were transplanted with PEPs. Inflammation and fibrosis were assessed by immunohistochemistry, bronchoalveolar lavage fluid differentials, and real-time polymerase chain reaction. Measurements and Main Results: PEPs expanded from mouse lungs were of bone marrow origin, coexpressed stem and hematopoietic cell markers, and differentiated in vitro into alveolar type II surfactant protein-C(+) epithelial cells. In bleomycin-challenged mice, intratracheally injected PEPs engrafted into the lungs and differentiated into type II pneumocytes. Furthermore, PEPs suppressed proinflammatory and profibrotic gene expression, prevented the recruitment of inflammatory cells, and protected bleomycin-challenged mice from pulmonary fibrosis. Mechanistically, the protective effect depended on upregulation of inducible nitric oxide synthase in PEPs and nitric oxide-mediated suppression of alveolar macrophage proliferation. Accordingly, PEPs from iNOS(-/-) but not iNOS(+/+) mice failed to protect from bleomycin-induced lung injury. Conclusions: The combined antiinflammatory and regenerative capacity of bone marrow-derived pulmonary epithelial progenitors offers a promising approach for development of cell-based therapeutic strategies against pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Two cases of Aerococcus urinae endocarditis are reported. The organism is not included in any database of commercial identification systems at this time. Formation of tetrades and positive reactions for leucine arylamidase and beta-glucuronidase pointed strongly to A. urinae. The cellular fatty acid pattern was similar to that of Aerococcus viridans, with predominantly C16∶0, C18∶1ω9c and C18∶0; the presence of C18∶1ω7t differentiated our isolates from A. viridans and can support the diagnosis of A. urinae. Furthermore, susceptibility to penicillin but resistance to cotrimoxazole represents a pattern opposite to that of A. viridans. Minimal inhibition concentrations of gentamicin and netilmicin were≤64 mg/l but those of tobramycin were≥256 mg/l. Penicillin combined with either gentamicin or netilmicin showed distinct synergy in killing kinetics. These combinations seem to be the appropriate regimen to treat A. urinae endocarditis. [ABSTRACT FROM AUTHOR]

Following the wave of COVID and the numerous protocols of INR -self-management for patients with LVAD, it has been demonstrated that patients can monitor and adjust their anticoagulation and achieve better time in therapeutic range (TTR) compared to standard monitoring and care by physicians. To achieve this goal, more INR tests are performed. Here we compare the TTR in self-management versus the standard treatment and the costs of these two strategies in a European context. Using a protocol established at St-Vincent Hospital in Australia, patients were offered to follow a training on anticoagulation and then manage their anti-vitamin K treatment independently (Auto-management). We then compared the TTR and the cost before and under this protocol. Costs are based on Swiss prices and converted into Dollars (1CHF=1.03US $). Test-strip cost $4.8 per unit, the lancet costs a few cents, and the INR machine (CoaguCheck) is available for $810. The combined cost of the blood test and its interpretation by a general physician (GP) is about $50. Since November 2021, 11 patients have been included in the protocol; these included no women, one patient with a HeartWare, and 10 with a HeartMate 3. The patients have been included in the protocol for a cumulative time of 80 months or a mean of 7.3 months per patient. One patient was transplanted, and none died. One patient had a haemorrhagic complication following colonoscopy under therapeutic INR (2.8), no patient suffered thrombosis, and no LVAD replacement was performed. We compare this group during the Standard Care (SC) and Auto-management (AM) period. During SC, the median TTR was 72% (IQR 63-78); during AM it increased to 90% (IQR 77-93). In SC, the INR control cost per day was $9.4 (IQR 6.6-13) on average, which decreased to $2.4 (IQR 1.9-2.6) per day in AM. INR monitoring occurred on average 5.9 (IQR 4.2-8.2) times per month in SC phase; while in AM patients measured their INR 13.1 (IQR 11.7-13.4) times per month. The cost of one day of INR within the therapeutic range was $13 under standard care, $5.0 in the first year on Auto-management. Despite being associated with more INR control, Self-management of anticoagulation by LVAD- patients are less expensive and results in a higher TTR. Self-management also promotes patient independence. It should be encouraged and expanded to other LVAD implant centres. [ABSTRACT FROM AUTHOR]

Background : Tafamidis reduces cardiovascular morbidity and mortality in transthyretin amyloid cardiomyopathy (ATTR-CM), yet availability and access to therapy vary. Objective : To determine how availability and access to tafamidis impact time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in ATTR-CM. Methods : Ninety-one consecutive ATTR-CM (~97% wt-TTR) patients diagnosed between June 2019 and June 2021 were evaluated for tafamidis. Access to therapy was regulated by compassionate use [n(CU) = 42] prior to, and insurance [n(IA) = 49] after regulatory approval. Results : Tafamidis was started in 37/42 (88.1%), and 39/49 (79.6%) patients, respectively. At diagnosis, ATTR-CM disease stage (≤stage 2: 88.2% vs. 90.9%, p = 0.92) was similar between groups. Timely access (after tafamidis approval) reduced the median time from first presentation to diagnosis from 6.2 (IQR: 1.3-28.9) to 2.4 (0.7-21.7) months, and from first presentation to therapy from 24.4 (10.7-46.8) to 11.8 (6.4-32.4) months. While RV function significantly worsened between diagnosis and therapy initiation in CU patients diagnosed before tafamidis approval (S'-velocity 10.0 ± 2.2 to 9.2 ± 2.2 cm/s; p = 0.018; TAPSE 17.3 ± 4.7 to 15.7 ± 3.9 mm, p = 0.008), it remained unchanged in IA patients (S'-velocity 9.6 ± 2.6 to 9.4 ± 2.3 cm/s; p = 0.83; TAPSE 15.6 ± 4.2 to 16.3 ± 3.1 mm, p = 0.45). After a median follow-up of 42.3 and 24.9 months in CU and IA patients, respectively, timely availability was associated with a reduction in annual heart failure hospitalizations (0.40 vs. 0.16 per patient, p < 0.001) and improved MACE-free survival (HR = 0.51; 95%CI: 0.26-1.00; p = 0.051). Timely diagnosis (<12-months) prolonged MACE-free survival (HR = 0.424; 95%CI: 0.22-0.81; p = 0.004), and reduced HFH (HR = 0.40; 95%CI: 0.19-0.81); p = 0.011) and all-cause mortality (HR = 0.29; 95%CI: 0.11-0.74); p = 0.009). Conclusions : Availability of tafamidis improves diagnostic efficacy in ATTR-CM patients. Timely diagnosis and initiation of therapy reduces adverse cardiovascular events.

Aims: This EUROMACS study was conducted with the primary aim of investigating the association between a centre's annual caseload and postoperative outcomes among patients undergoing left ventricular assist device (LVAD) implantation., Methods and Results: A total of 4802 patients identified between 2011 and 2020 from 35 participating centres were dichotomized based on the annual caseload of the treating centre at the time of device implant (≤30 vs. >30 LVAD implantations/year). The primary endpoint was 1-year survival. Secondary outcomes included overall survival analysis, device-related adverse events and readmissions. Cumulative follow-up was 10 003 patient-years, with a median follow-up of 1.54 years (interquartile range 0.52-3.15). Patients from higher volume centres more frequently presented in INTERMACS levels 1 and 2, suffered from right heart dysfunction and needed inotropic support. No difference was observed in adjusted 1-year survival. Adjusted overall survival probability was lower in higher volume centres (p = 0.002). In the subgroup analysis of HeartMate 3 devices only, higher volume centres were associated with decreased odds of 1-year survival (adjusted odds ratio 0.43, 95% confidence interval 0.20-0.97, p = 0.041). Similar findings were observed in the cumulative (i.e. learning curve) caseload analyses., Conclusion: In patients undergoing LVAD implantation, centre volume was not associated with 1-year survival, but was related to device-related adverse events. Patient profiles differed with respect to centre size. These findings underscore the necessity for ongoing quality improvement initiatives in all centres, regardless of their annual caseload. Efforts are needed to standardize patient selection and preconditioning to further improve patient outcome., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Tafamidis improves clinical outcomes in transthyretin amyloid cardiomyopathy (ATTR-CM), yet how tafamidis affects cardiac structure and function remains poorly described. This study prospectively analysed the effect of tafamidis on 12-month longitudinal changes in cardiac structure and function by cardiac magnetic resonance (CMR) compared with the natural course of disease in an untreated historic control cohort., Methods and Results: ATTR-CM patients underwent CMR at tafamidis initiation and at 12 months. Untreated patients with serial CMRs served as reference to compare biventricular function, global longitudinal strain (GLS), LV mass and extracellular volume fraction (ECV). Thirty-six tafamidis-treated (n = 35; 97.1% male) and 15 untreated patients (n = 14; 93.3% male) with a mean age of 78.3 ± 6.5 and 76.9 ± 6.5, respectively, and comparable baseline characteristics were included. Tafamidis was associated with preserving biventricular function (LVEF (%): 50.5 ± 12 to 50.7 ± 11.5, P = 0.87; RVEF (%): 48.2 ± 10.4 to 48.2 ± 9.4, P = 0.99) and LV-GLS (-9.6 ± 3.2 to -9.9 ± 2.4%; P = 0.595) at 12 months, while a significantly reduced RV-function (50.8 ± 7.3 to 44.2 ± 11.6%, P = 0.028; P (change over time between groups) = 0.032) and numerically worsening LVGLS (-10.9 ± 3.3 to -9.1 ± 2.9%, P = 0.097; P (change over time between groups) = 0.048) was observed without treatment. LV mass significantly declined with tafamidis (184.7 ± 47.7 to 176.5 ± 44.3 g; P = 0.011), yet remained unchanged in untreated patients (163.8 ± 47.5 to 171.2 ± 39.7 g P = 0.356, P (change over time between groups) = 0.027). Irrespective of tafamidis, ECV and native T1-mapping did not change significantly from baseline to 12-month follow-up (P > 0.05)., Conclusions: Compared with untreated ATTR-CM patients, initiation of tafamidis preserved CMR-measured biventricular function and reduced LV mass at 12 months. ECV and native T1-mapping did not change significantly comparable to baseline in both groups., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: To optimize right ventricular-pulmonary coupling during veno-arterial (VA) ECMO weaning, inotropes, vasopressors and/or vasodilators are used to change right ventricular (RV) function (contractility) and pulmonary artery (PA) elastance (afterload). RV-PA coupling is the ratio between right ventricular contractility and pulmonary vascular elastance and as such, is a measure of optimized crosstalk between ventricle and vasculature. Little is known about the physiology of RV-PA coupling during VA ECMO. This study describes adaptive mechanisms for maintaining RV-PA coupling resulting from changing pre- and afterload conditions in VA ECMO., Methods: In 13 pigs, extracorporeal flow was reduced from 4 to 1 L/min at baseline and increased afterload (pulmonary embolism and hypoxic vasoconstriction). Pressure and flow signals estimated right ventricular end-systolic elastance and pulmonary arterial elastance. Linear mixed-effect models estimated the association between conditions and elastance., Results: At no extracorporeal flow, end-systolic elastance increased from 0.83 [0.66 to 1.00] mmHg/mL at baseline by 0.44 [0.29 to 0.59] mmHg/mL with pulmonary embolism and by 1.36 [1.21 to 1.51] mmHg/mL with hypoxic pulmonary vasoconstriction (p < 0.001). Pulmonary arterial elastance increased from 0.39 [0.30 to 0.49] mmHg/mL at baseline by 0.36 [0.27 to 0.44] mmHg/mL with pulmonary embolism and by 0.75 [0.67 to 0.84] mmHg/mL with hypoxic pulmonary vasoconstriction (p < 0.001). Coupling remained unchanged (2.1 [1.8 to 2.3] mmHg/mL at baseline; - 0.1 [- 0.3 to 0.1] mmHg/mL increase with pulmonary embolism; - 0.2 [- 0.4 to 0.0] mmHg/mL with hypoxic pulmonary vasoconstriction, p > 0.05). Extracorporeal flow did not change coupling (0.0 [- 0.0 to 0.1] per change of 1 L/min, p > 0.05). End-diastolic volume increased with decreasing extracorporeal flow (7.2 [6.6 to 7.8] ml change per 1 L/min, p < 0.001)., Conclusions: The right ventricle dilates with increased preload and increases its contractility in response to afterload changes to maintain ventricular-arterial coupling during VA extracorporeal membrane oxygenation., (© 2024. The Author(s).)

Background: Evidence to support immediate P2Y 12 inhibitor loading in ST-segment elevation myocardial infarction (STEMI) is limited., Objectives: This study sought to compare outcomes of STEMI patients receiving immediate or delayed P2Y 12 inhibitor treatment., Methods: Using data from the prospective Bern-PCI registry between 2016 and 2020, we stratified STEMI patients undergoing percutaneous coronary intervention according to time periods with different institutional recommendations regarding P2Y 12 inhibitor pretreatment. In cohort 1 (October 2016-September 2018), immediate P2Y 12 inhibitor treatment was recommended. In cohort 2 (October 2018-September 2020), P2Y 12 inhibitor treatment was recommended after coronary anatomy was confirmed. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events (MACCEs) defined as all-cause death, recurrent myocardial infarction, stroke, or definite stent thrombosis at 30 days. Sensitivity analysis included only patients in whom these recommendations were followed., Results: Cohort 1 included 1,116 patients; pretreatment was actually given in 708 (63.4%). Cohort 2 included 847 patients; pretreatment was withheld in 798 (94.2%). The mean age was 65 ± 13 years, and 24% were female. Baseline characteristics were well-balanced between groups. The median difference for P2Y 12 loading to angiography was 52 minutes between cohort 1 and 2 and 100 minutes between patients receiving vs not receiving pretreatment. Rates of MACCEs were similar between cohort 1 and cohort 2 (10.1% vs 8.1%; adjusted HR: 0.91; 95% CI: 0.65-1.28; P = 0.59) and between patients receiving vs not receiving pretreatment (7.1% vs 8.4%; adjusted HR: 1.17; 95% CI: 0.78-1.74; P = 0.45)., Conclusions: In this cohort study of patients with STEMI undergoing primary percutaneous coronary intervention, P2Y 12 inhibitor pretreatment was not associated with improved MACCEs., Competing Interests: Funding Support and Author Disclosures Dr Rohla has received advisory fees from Daiichi Sankyo, Sanofi Aventis, COR2ED, Novartis and Medtronic; and has received lecturing fees from Daiichi Sankyo, Biotronik, and Takeda Pharma, all outside of the submitted work. Dr Stortecky has received research grants to the institution from Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific; and has received speaker fees from Boston Scientific. Dr Praz has received travel expenses from Abbott Vascular, Polares Medical, and Edwards Lifesciences. Dr Pilgrim has received research grants to the institution from Medtronic, Abbott, Biotronik, Boston Scientific, and Edwards Lifesciences; and has received speaker fees/consultancy from Medtronic, Biotronik, Boston Scientific, Abbott, and HighLife SAS. Dr Windecker reports research, travel, or educational grants to the institution without personal remuneration from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Braun, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Cordis Medical, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Farapulse Inc Fumedica, Guerbet, Idorsia, Inari Medical, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medalliance, Medicure, Medtronic, Merck Sharp and Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pharming Tech. Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave; has served as an advisory board member and/or member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, and V-Wave with payments to the institution but no personal payments; is member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration; is vice president of the European Society of Cardiology; and is associate editor of the JACC: Cardiovascular Interventions. Dr Räber has received research grants to the institution by Abbott, Biotronik, Heartflow, Sanofi, and Regeneron; and has received speaker/consultation fees from Abbott, Amgen, AstraZeneca, Canon, Novo Nordisk, Medtronic, Sanofi, Occlutech, and Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The optimal time point of staged percutaneous coronary intervention (PCI) among patients with acute coronary syndrome (ACS) remains a matter of debate. Quantitative flow ratio (QFR) is a novel noninvasive method to assess the hemodynamic significance of coronary stenoses. We aimed to investigate whether QFR could refine the timing of staged PCI of non-target vessels (non-TVs) on top of clinical judgment for patients with ACS., Methods and Results: For this cohort study, patients with ACS from Bern University Hospital, Switzerland, scheduled to undergo out-of-hospital non-TV staged PCI were eligible. The primary end point was the composite of non-TV myocardial infarction and urgent unplanned non-TV PCI before planned staged PCI. The association between lowest QFR per patient measured in the non-TV (from index angiogram) and the primary end point was assessed using multivariable adjusted Cox proportional hazards regressions with QFR included as linear or penalized spline (nonlinear) term. QFR was measured in 1093 of 1432 patients with ACS scheduled to undergo non-TV staged PCI. Median time to staged PCI was 28 days. The primary end point occurred in 5% of the patients. In multivariable analysis (1018 patients), there was no independent association between non-TV QFR and the primary end point (hazard ratio, 0.87 [95% CI, 0.69-1.05] per 0.1 increase; P =0.125; nonlinear P =0.648)., Conclusions: In selected patients with ACS scheduled to undergo staged PCI at a median of 4 weeks after index PCI, QFR did not emerge as an independent predictor of non-TV events before planned staged PCI. Thus, this study does not provide conceptual evidence that QFR is helpful to refine the timing of staged PCI on top of clinical judgment., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02241291.

Background: Type 2 diabetes (T2D) is expected to worsen the prognosis of inpatients with heart failure (HF) but the evidence from observational studies is inconsistent. We aimed to compare mortality outcomes and life expectancy among inpatients with HF with or without T2D and explored whether chronic kidney disease (CKD) influenced these associations., Methods: We collected hospital and civil registry records of consecutive inpatients from a tertiary hospital in Switzerland with a diagnosis of HF from the year 2015 to 2019. We evaluated the association of T2D with mortality risk using Cox regression and adjusted for confounders., Results: Our final cohort consisted of 10,532 patients with HF of whom 27% had T2D. The median age (interquartile range [IQR]) was 75 [68 to 82] and 78 [68 to 86] for the diabetes and non-diabetes groups, respectively. Over a median follow-up [IQR] of 4.5 years [3.3 to 5.6], 5,347 (51%) of patients died. T2D patients had higher risk of all-cause mortality (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.14 to 1.29). Compared to control (i.e. no T2D nor CKD), average life expectancy (95% CI) among T2D patients, CKD, or both was shorter by 5.4 months (95% CI 1.1 to 9.7), 9.0 months (95% CI 8.4 to 9.6), or 14.8 months (95% CI 12.4 to 17.2), respectively. No difference by sex or ejection fraction category was observed., Conclusions: T2D is associated with a significantly higher risk of all-cause mortality and shorter life expectancy compared to those without among middle-aged and elderly inpatients with HF; presence of CKD may further increase these risks., (© 2023. The Author(s).)

Background: The number of patients treated by ventricular assist devices (VAD) and the duration of VAD treatment is increasing. One of the main complications in terms of morbidity and mortality for VAD patients are microbial infections. With this study, we aimed to investigate the epidemiology and microbiological characteristics of infections occurring in a VAD population to identify modifiable factors., Methods: We retrospectively analyzed patient characteristics, treatments and outcomes of VAD-specific/related infections. All patients implanted in our institution with a continuous flow VAD between January 2009 and January 2019 were included. Risk factors for VAD infection were assessed using simple and multiple linear regressions., Results: Of the 104 patients screened, 99 were included in the analysis, the majority of which were men (78%). At implantation, the mean age was 56 years and the median time on VAD support was 541 days. The overall infection rate per year per patient was 1.4. Forty-seven patients (60%) suffered from VAD-specific/related infection. Half of all infection episodes occurred in the first 4 months but the proportion of VAD-specific/related infection was higher after the first 4 months (74% of all infection). Using regression models, no patient specific risk factors were associated with VAD-specific/related infections., Conclusion: No predictive factors for infection during VAD support were identified in this study. By extension, diabetes, renal insufficiency, age or high BMI are not sufficient to deny a patient access to ventricular support., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Objective: Digital healthcare systems could provide insights into the global prevalence of heart failure (HF). We designed the CardioRenal and Metabolic disease (CaReMe) HF study to estimate the prevalence, key clinical adverse outcomes and costs of HF across 11 countries., Methods: Individual level data from a contemporary cohort of 6 29 624 patients with diagnosed HF was obtained from digital healthcare systems in participating countries using a prespecified, common study plan, and summarised using a random effects meta-analysis. A broad definition of HF (any registered HF diagnosis) and a strict definition (history of hospitalisation for HF) were used. Event rates were reported per 100 patient years. Cumulative hospital care costs per patient were calculated for a period of up to 5 years., Results: The prevalence of HF was 2.01% (95% CI 1.65 to 2.36) and 1.05% (0.85 to 1.25) according to the broad and strict definitions, respectively. In patients with HF (broad definition), mean age was 75.2 years (95% CI 74.0 to 76.4), 48.8% (40.9-56.8%) had ischaemic heart disease and 34.5% (29.4-39.6%) had diabetes. In 51 442 patients with a recorded ejection fraction (EF), 39.1% (30.3-47.8%) had a reduced, 18.8% (13.5-24.0%) had a mildly reduced and 42.1% (31.5-52.8%) had a preserved left ventricular EF. In 1 69 518 patients with recorded estimated glomerular filtration rate, 49% had chronic kidney disease (CKD) stages III-V. Event rates were highest for cardiorenal disease (HF or CKD) and all cause mortality (19.3 (95% CI 11.3 to 27.1) and 13.1 (11.1 to 15.1), respectively), and lower for myocardial infarction, stroke and peripheral artery disease. Hospital care costs were highest for cardiorenal diseases., Conclusions: We estimate that 1-2% of the contemporary adult population has HF. These individuals are at significant risk of adverse outcomes and associated costs, predominantly driven by hospitalisations for HF or CKD. There is considerable public health potential in understanding the contemporary burden of HF and the importance of optimising its management., Competing Interests: Competing interests: AN has received honoraria from MSD, AstraZeneca, Eli Lilly, Boehringer Ingelheim and Novo Nordisk. JB holds a full time position at AstraZeneca as an epidemiologist. NT reports grants and personal fees from AstraZeneca, grants and personal fees from Janssen, grants and personal fees from BI-Lilly, grants and personal fees from Otsuka, grants, personal fees and other from Tricida, personal fees and other from Pulsedata, personal fees and other from Mesentech, personal fees and other from Renibus, and other from ClinPredict, outside the submitted work; NT has a patent for a microfluidic device for point of care detection of urine albumin pending. AK has received research grants and speaking honoraria from Astrazeneca, Novonordisk and Boehringer Ingelheim. APM reports receiving fees for serving on study committees from AstraZeneca, Novartis, Bayer and Fresenius, outside the present work. TT-G declares speaker and consulting fees from AstraZeneca, BIAL, Daiichi-Sankyo, MSD, Medinfar and Novartis; TT-G holds shares in MTG. MB has received honoraria from Astra Zeneca, Janssen, Lilly, Boehringer Ingelheim, Sanofi, Amgen and Novo Nordisk. MT holds a full time position by an independent statistical consultant company, Statisticon AB, Uppsala, Sweden, of which AstraZeneca Nordic is a client. JS reports stock ownership in companies providing services to Itrim, Amgen, Janssen, Novo Nordisk, Eli Lilly, Boehringer, Bayer, Pfizer, Takeda and AstraZeneca, outside the submitted work. AB is supported by research funding from NIHR, British Medical Association, AstraZeneca and UK Research and Innovation. ABo is part of the BigData@Heart Consortium, funded by the Innovative Medicines Initiative-2 Joint Undertaking under grant agreement No 116074; this joint undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. KAS has received speaking honoraria from Astrazeneca, Novonordisk, Sanofi and Boehringer Ingelheim., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: According to current guidelines, hemodynamic status should guide the decision between immediate and delayed coronary angiography (CAG) in out-of-hospital cardiac arrest (OHCA) patients without ST-segment elevation. A delayed strategy is advised in hemodynamically stable patients, and an immediate approach is recommended in unstable patients., Objectives: This study sought to assess the frequency, predictors, and clinical impact of acute coronary occlusion in hemodynamically stable and unstable OHCA patients without ST-segment elevation., Methods: Consecutive unconscious OHCA patients without ST-segment elevation who were undergoing CAG at Bern University Hospital (Bern, Switzerland) between 2011 and 2019 were included. Frequency and predictors of acute coronary artery occlusions and their impact on all-cause and cardiovascular mortality at 1 year were assessed., Results: Among the 386 patients, 169 (43.8%) were hemodynamically stable. Acute coronary occlusions were found in 19.5% of stable and 24.0% of unstable OHCA patients (P = 0.407), and the presence of these occlusions was predicted by initial chest pain and shockable rhythm, but not by hemodynamic status. Acute coronary occlusion was associated with an increased risk of cardiovascular death (adjusted HR: 2.74; 95% CI: 1.22-6.15) but not of all-cause death (adjusted HR: 0.72; 95% CI: 0.44-1.18). Hemodynamic instability was not predictive of fatal outcomes., Conclusions: Acute coronary artery occlusions were found in 1 in 5 OHCA patients without ST-segment elevation. The frequency of these occlusions did not differ between stable and unstable patients, and the occlusions were associated with a higher risk of cardiovascular death. In OHCA patients without ST-segment elevation, chest pain or shockable rhythm rather than hemodynamic status identifies patients with acute coronary occlusion., Competing Interests: Funding Support and Author Disclosures This study was supported by the Department of Cardiology at Bern University Hospital, Bern, Switzerland. Dr Spirito has received a research grant from the Swiss National Science Foundation. Dr Bär has received research grants from Medis Medical Imaging Systems, Abbott, Bangerter-Rhyner-Stiftung, and the Swiss National Science Foundation, outside the submitted work. Dr Valgimigli has received personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Bayer, CoreFLOW, Idorsia Pharmaceuticals, University of Basel Clinical Research Department, Vifor, Bristol Myers Squibb, Biotronik, Boston Scientific, Medtronic, Vesalio, Novartis, Chiesi, and PhaseBio; and has received grants and personal fees from Terumo, outside the submitted work. Dr Windecker has received research and educational grants to the institution from Abbott, Amgen, AstraZeneca, Bristol Myers Squibb, Bayer, Biotronik, Boston Scientific, Cardinal Health, CardioValve, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Johnson & Johnson, Medicure, Medtronic, Novartis, Polares, OrPha Suisse, Pfizer, Regeneron, Sanofi, Sinomed, Terumo, and V-Wave; has served as an unpaid advisory board member and/or unpaid member of the steering or executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer. Bristol Myers Squibb, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis but has not received personal payments from pharmaceutical companies or device manufacturers; and is a member of the steering or executive committee group of several investigator-initiated trials that receive funding from industry without an impact on his personal remuneration. Dr Räber has received research grants to the institution from Abbott, Biotronik, Boston Scientific, Heartflow, Sanofi, and Regeneron; and has received speaker or consultation fees from Abbott, Amgen, AstraZeneca, Canon, Medtronic, NovoNordisk, Occlutech, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in heart failure patients with reduced and preserved left ventricular ejection fraction (LVEF), but have not yet been investigated in transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to evaluate tolerability, clinical outcomes, and changes in NT-proBNP levels and glomerular filtration rate (GFR) in ATTR-CM patients treated with dapagliflozin., Methods and Results: Patients with stable, tafamidis-treated ATTR-CM were retrospectively evaluated at the initiation of dapagliflozin and 3 months thereafter. Tafamidis-treated ATTR-CM patients without SGLT2i served as a reference cohort. Overall, SLGT2i therapy was initiated in 34 patients. Seventeen patients with stable disease on tafamidis, who were subsequently started on dapagliflozin, were included in the analysis. Patients selected for SGLT2i presented with signs of advanced disease, evidenced by higher Gillmore disease stage (stage ≥2: 53% vs. 27.5%; P = 0.041), baseline median NT-proBNP [median (IQR) 2668 pg/mL (1314-3451) vs. 1424 (810-2059); P = 0.038] and loop diuretic demand (76.5% vs. 45% of patients; P = 0.044), and lower LVEF (46.6 ± 12.9 vs. 53.7 ± 8.7%; P = 0.019) and GFR (51.8 ± 16.5 vs. 68.5 ± 18.6 mL/min; P = 0.037) compared with the reference cohort. At 3-month follow-up, a numerical decrease in NT-proBNP levels was observed in 13/17 (76.5%) patients in the dapagliflozin (-190 pg/mL, IQR: -1,028-71, P = 0.557) and 27/40 (67.5%) of patients in the control cohort (-115 pg/mL, IQR: -357-105, P = 0.551). Other disease parameters remained stable and no adverse events occurred., Conclusions: In tafamidis-treated ATTR-CM patients, initiation of dapagliflozin was well tolerated. The efficacy of SGLT2i therapy in patients with ATTR-CM needs to be studied in randomized controlled trials., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)