Case report: desmoplakin cardiomyopathy presenting as an inflammatory cardiomyopathy with repeated sudden cardiac arrests.

Background: Desmoplakin cardiomyopathy has been recently classified as a non-dilated left ventricular cardiomyopathy, which is characterized by inflammatory-like episodes followed by left ventricular fibrosis/dysfunction and ventricular arrhythmias. Specific management is unclear. Case summary: We report a detailed case of a 46-year-old Caucasian woman presenting with repeated sudden cardiac arrests who was diagnosed with a new variant in the desmoplakin gene. Because the initial 18F-fluorodeoxyglucose positron emission tomography scan showed significant hypermetabolism, she was treated with immunosuppressors, with only minimal improvement on imaging. Discussion: Desmoplakin cardiomyopathy should be considered in the differential diagnosis of inflammatory cardiomyopathies. Little is known about the use of immunosuppressive treatments, but it could be reasonable for some selected patients.

Association Between Patient Sex and Familial Hypercholesterolemia and Long-Term Cardiovascular Risk Factor Management 5 Years After Acute Coronary Syndrome.

BACKGROUND: Long-term control of cardiovascular risk factors after acute coronary syndrome (ACS) is the cornerstone for preventing recurrence. We investigated the extent of cardiovascular risk factor management in males and females with and without familial hypercholesterolemia (FH) 5 years after ACS. METHODS: We studied patients hospitalized for ACS between 2009 and 2017 in a Swiss multicenter prospective cohort study. FH was defined based on clinical criteria from the Dutch Lipid Clinic Network and Simon Broome definitions. Five years post-ACS, we assessed low-density lipoprotein-cholesterol (LDL-c) levels, lipid-lowering therapy (LLT), and other cardiovascular risk factors, comparing males to females with and without FH using generalized estimating equations. RESULTS: A total of 3139 patients were included; mean age was 61.4 years (SD, 12.1), 620 (19.8%) were female, and 747 (23.5%) had possible FH. Compared with males at 5-years post-ACS, females were more likely to not use statins (odds ratio, 1.61 [95% CI, 1.28-2.03]) and less likely to have combination LLT (odds ratio, 0.72 [95% CI, 0.55-0.93]), without difference between patients with FH and without FH. Females in both FH and non-FH groups less frequently reached LDL-c values ≤1.8 mmol/L (odds ratio, 0.78 [95% CI, 0.78-0.93]). Overall, patients with FH were more frequently on high-dose statins compared with patients without FH (51.0% versus 42.9%; P=0.001) and presented more frequently with a combination of 2 or more LLT compared with patients without FH (33.8% versus 17.7%; P<0.001), but less frequently reached LDL-c targets of ≤1.8 mmol/L (33.5% versus 44.3%; P<0.001) or ≤2.6 mmol/L (70.2% versus 78.1%; P=0.001). CONCLUSIONS: Five years after ACS, females had less intensive LLT and were less likely to reach target LDL-c levels than males, regardless of FH status. Males and females with FH had less optimal control of LDL-c despite more frequently taking high-dose statins or combination LLT compared with patients without FH. Long-term management of patients with ACS and FH, especially females, warrants optimization.

Impact of the 2021 European Society for Cardiology prevention guideline's stepwise approach for cardiovascular risk factor treatment in patients with established atherosclerotic cardiovascular disease.

AIMS: This study aimed to evaluate the stepwise approach for cardiovascular (CV) risk factor treatment as outlined by the European Society for Cardiology 2021 guidelines on CV disease (CVD) prevention in patients with established atherosclerotic CVD (ASCVD). METHODS AND RESULTS: In patients with ASCVD, included in UCC-SMART (n = 8730) and European parts of the REACH registry (n = 18 364), the 10-year CV risk was estimated using SMART2. Treatment effects were derived from meta-analyses and trials. Step 1 recommendations were LDL cholesterol (LDLc) < 1.8 mmol/L, systolic blood pressure (SBP) < 140 mmHg, using any antithrombotic medication, sodium-glucose co-transporter 2 (SGLT2) inhibition, and smoking cessation. Step 2 recommendations were LDLc < 1.4 mmol/L, SBP < 130 mmHg, dual-pathway inhibition (DPI, aspirin plus low-dose rivaroxaban), colchicine, glucagon-like peptide (GLP)-1 receptor agonists, and eicosapentaenoic acid. Step 2 was modelled accounting for Step 1 non-attainment. With current treatment, residual CV risk was 22%, 32%, and 60% in the low, moderate, and pooled (very) high European risk regions, respectively. Step 2 could prevent up to 198, 223 and 245 events per 1000 patients treated, respectively. Intensified LDLc reduction, colchicine, and DPI could be applied to most patients, preventing up to 57, 74, and 59 events per 1000 patients treated, respectively. Following Step 2, the number of patients with a CV risk of <10% could increase from 20%, 6.4%, and 0.5%, following Step 1, to 63%, 48%, and 12%, in the respective risk regions. CONCLUSION: With current treatment, residual CV risk in patients with ASCVD remains high across all European risk regions. The intensified Step 2 treatment options result in marked further reduction of residual CV risk in patients with established ASCVD. KEY FINDINGS: Guideline-recommended intensive treatment of patients with cardiovascular disease could prevent additional 198-245 new cardiovascular events for every 1000 patients treated.

Patients with established cardiovascular disease are at high risk for new cardiovascular events. The European Society of Cardiology guideline for the prevention of cardiovascular disease introduced a stepwise treatment approach. Step 1 in this approach are treatments that apply to all patients, and Step 2 are intensive treatments that can be prescribed to patients who are still at high risk of new events even with Step 1 treatments. The current study investigates the effect of Steps 1 and 2 on the risk of cardiovascular disease in 27 094 patients all across Europe. With the conventional treatments of Step 1 the risk of cardiovascular disease remains high, with a 10-year risk of new events higher than 10% in 80­99% of patients. The intensive treatment options from Step 2 could prevent additional 198­245 new cardiovascular events for every 1000 patients that are treated. With intensive treatment, up to 63% of patients could achieve a 10-year risk of new cardiovascular disease below 10%.

Drinking patterns of alcohol and risk of major adverse cardiovascular events after an acute coronary syndrome.

AIM: To evaluate the risk of alcohol consumption after acute coronary syndromes (ACS). METHODS: A total of 6557 patients hospitalized for ACS at 4 Swiss centres were followed over 12 months. Weekly alcohol consumption was collected at baseline and 12 months. Binge drinking was defined as consumption of ≥6 units of alcohol on one occasion. Major adverse cardiovascular events (MACE) were defined as a composite of cardiac death, myocardial infarction, stroke or clinically indicated target vessel coronary revascularization. Cox regression analysis was performed to assess the risk of MACE in patients with heavy (>14 standard units/week), moderate (7-14 standard units per week), light consumption (<1 standard unit/week) or abstinence, and with binge drinking episodes, adjusted for baseline differences. RESULTS: At baseline, 817 (13.4%) patients reported heavy weekly alcohol consumption. At one-year follow-up, 695/1667 (41.6%) patients reported having at least one or more episodes of binge drinking per month. The risk for MACE was not significantly higher in those with heavy weekly consumption compared to abstinence (8.6% vs. 10.2%, HR 0.97, 95%CI 0.69-1.36) or light consumption (8.6% vs. 8.5 %, HR 1.41, 95%CI 0.97-2.06). Compared to patients with no-binge drinking, the risk of MACE was dose-dependently higher in those with binge drinking with less than one episode per month (9.2% vs 7.8%, HR 1.61, 95%CI 1.23-2.11), or one or more episodes per month (13.6% vs 7.8%, HR 2.17, 95%CI 1.66-2.83). CONCLUSION: Binge drinking during the year following an ACS, even less than once per month, is associated with worse clinical outcomes.

The cardiovascular risk of alcohol consumption and of binge drinking episodes after acute coronary syndrome (ACS) has not been established. Our data suggested the following: After ACS, regular weekly alcohol consumption is not associated with the risk of major adverse cardiovascular events (MACE), except for patients reporting binge drinking who have a two-fold increased risk of MACE within one year of the index event.After ACS, episodes of binge drinking, even less than once per month, are associated with worse clinical outcomes. It is not the frequency, but rather the quantity of alcohol intake in a binge drinking episode, that is associated with worse prognosis in patients after an ACS.

Effects of SARS-COV-2 infection on outcomes in patients hospitalized for acute cardiac conditions. A prospective, multicenter cohort study (Swiss Cardiovascular SARS-CoV-2 Consortium).

Background: Although the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) causing coronavirus disease 2019 (COVID-19) primarily affects the respiratory system, the disease entity has been associated with cardiovascular complications. This study sought to assess the effect of concomitant SARS-COV-2 infection on clinical outcomes of patients hospitalized primarily for acute cardiac conditions on cardiology wards in Switzerland. Methods: In this prospective, observational study conducted in 5 Swiss cardiology centers during the COVID-19 pandemic, patients hospitalized due to acute cardiac conditions underwent a reverse-transcriptase polymerase chain reaction test at the time of admission and were categorized as SARS-COV-2 positive (cases) or negative (controls). Patients hospitalized on cardiology wards underwent treatment for the principal acute cardiac condition according to local practice. Clinical outcomes were recorded in-hospital, at 30 days, and after 1 year and compared between cases and controls. To adjust for imbalanced baseline characteristics, a subgroup of patients derived by propensity matching was analyzed. Results: Between March 2020 and February 2022, 538 patients were enrolled including 122 cases and 416 controls. Mean age was 68.0 ± 14.7 years, and 75% were men. Compared with controls, SARS-COV-2-positive patients more commonly presented with acute heart failure (35% vs. 17%) or major arrhythmia (31% vs. 9%), but less commonly with acute coronary syndrome (26% vs. 53%) or severe aortic stenosis (4% vs. 18%). Mortality was significantly higher in cases vs. controls in-hospital (16% vs. 1%), at 30 days (19.0% vs. 2.2%), and at 1 year (28.7% vs. 7.6%: p < 0.001 for all); this was driven primarily (up to 30 days) and exclusively (at one-year follow-up) by higher non-cardiovascular mortality, and was accompanied by a greater incidence of worsening renal function in cases vs. controls. These findings were maintained in a propensity-matched subgroup of 186 patients (93 cases and 93 controls) with balanced clinical presentation and baseline characteristics. Conclusions: In this observational study of patients hospitalized for acute cardiac conditions, SARS-COV-2 infection at index hospitalization was associated with markedly higher all-cause and non-cardiovascular mortality throughout one-year follow-up. These findings highlight the need for effective, multifaceted management of both cardiac and non-cardiac morbidities and prolonged surveillance in patients with acute cardiac conditions complicated by SARS-COV-2 infection.

[Acetazolamide in acute heart failure]. / Utilisation de l'acétazolamide dans l'insuffisance cardiaque aiguë.

Acute heart failure is a leading cause of hospitalisations with an increasing economic and public health burden. Management of acute heart failure involves the use of diuretics to treat congestion and improve morbimortality. Despite current guidelines, numerous patients maintain congestion and often leave the hospital setting with incomplete volume depletion, leading to an increased risk of rehospitalisation. A recent multicentric randomised controlled trial studied the administration of acetazolamide in addition to standard care with loop diuretics in the acute setting. There was a significantly faster decongestion, based on a pragmatic clinical score, with very few side effects.

L'insuffisance cardiaque est la première cause d'hospitalisation dans les pays occidentaux, engendrant un coût médico-économique important. La prise en charge médicamenteuse de l'insuffisance cardiaque aiguë comprend l'administration de diurétiques afin de traiter la congestion et d'améliorer la morbimortalité. Toutefois, de nombreux patients présentent encore une congestion importante après plusieurs jours de traitement diurétique et rentrent à domicile avec une congestion résiduelle, augmentant le risque de récidive de décompensation cardiaque et par conséquent de ré-hospitalisation. Dans une étude randomisée multicentrique en double-aveugle, l'acétazolamide utilisé en adjonction d'un traitement diurétique de l'anse a permis une décongestion significativement plus rapide et efficace sans augmentation notable des effets indésirables.

Mesoamerican urbanism revisited: Environmental change, adaptation, resilience, persistence, and collapse.

Urban adaptation to climate change is a global challenge requiring a broad response that can be informed by how urban societies in the past responded to environmental shocks. Yet, interdisciplinary efforts to leverage insights from the urban past have been stymied by disciplinary silos and entrenched misconceptions regarding the nature and diversity of premodern human settlements and institutions, especially in the case of prehispanic Mesoamerica. Long recognized as a distinct cultural region, prehispanic Mesoamerica was the setting for one of the world's original urbanization episodes despite the impediments to communication and resource extraction due to the lack of beasts of burden and wheeled transport, and the limited and relatively late use of metal implements. Our knowledge of prehispanic urbanism in Mesoamerica has been significantly enhanced over the past two decades due to significant advances in excavating, analyzing, and contextualizing archaeological materials. We now understand that Mesoamerican urbanism was as much a story about resilience and adaptation to environmental change as it was about collapse. Here we call for a dialogue among Mesoamerican urban archaeologists, sustainability scientists, and researchers interested in urban adaptation to climate change through a synthetic perspective on the organizational diversity of urbanism. Such a dialogue, seeking insights into what facilitates and hinders urban adaptation to environmental change, can be animated by shifting the long-held emphasis on failure and collapse to a more empirically grounded account of resilience and the factors that fostered adaptation and sustainability.

Cardiovascular therapy use, modification, and in-hospital death in patients with COVID-19: A cohort study.

AIMS: To assess the associations of exposure and modifications in exposure (i.e., discontinuation on admission, initiation during hospitalization) to eight common cardiovascular therapies with the risk of in-hospital death among inpatients with coronavirus disease 2019 (COVID-19). METHODS: In this observational study including 838 hospitalized unvaccinated adult patients with confirmed COVID-19, the use of cardiovascular therapies was assessed using logistic regression models adjusted for potential confounders. RESULTS: No cardiovascular therapy used before hospitalization was associated with an increased risk of in-hospital death. During hospitalization, the use of diuretics (aOR 2.59 [1.68-3.98]) was associated with an increase, and the use of agents acting on the renin-angiotensin system (aOR 0.39 [0.23-0.64]) and lipid-lowering agents (aOR 0.41 [0.24-0.68]) was associated with a reduction in the odds of in-hospital death. Exposure modifications associated with decreased survival were the discontinuation of an agent acting on the renin-angiotensin system (aOR 4.42 [2.08-9.37]), a ß-blocker (aOR 5.44 [1.16-25.46]), a lipid-modifying agent (aOR 3.26 [1.42-7.50]) or an anticoagulant (aOR 5.85 [1.25-27.27]), as well as the initiation of a diuretic (aOR 5.19 [2.98-9.03]) or an antiarrhythmic (aOR 6.62 [2.07-21.15]). Exposure modification associated with improved survival was the initiation of an agent acting on the renin-angiotensin system (aOR 0.17 [0.03-0.82]). CONCLUSION: In hospitalized and unvaccinated patients with COVID-19, there was no detrimental association of the prehospital use of any regular cardiovascular medication with in-hospital death, and these therapies should be continued as recommended.

Mammalian Target of Rapamycin Inhibition in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Early inflammation following acute ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) affects myocardial infarct (MI) size and left ventricular remodeling. The mammalian target of rapamycin (mTOR) is involved in the enhanced inflammatory response and its inhibition has exerted beneficial effects on MI size in preclinical models of acute MI. OBJECTIVES: The CLEVER-ACS (Controlled Level Everolimus in Acute Coronary Syndromes) trial evaluated the effects of targeting inflammation by mTOR inhibition in patients with STEMI undergoing PCI. METHODS: CLEVER-ACS was a randomized, multicenter, international, double-blind, placebo-controlled trial. A total of 150 patients with STEMI undergoing PCI were randomly assigned to oral everolimus (days 1-3: 7.5 mg daily; days 4-5: 5.0 mg daily) or placebo for 5 days. The primary endpoint was the change in MI size. The secondary endpoint was the change in microvascular obstruction (MVO) from baseline (12 hours to 5 days after PCI) to 30 days as assessed by cardiac magnetic resonance imaging. RESULTS: The changes in MI size from baseline to 30 days, the primary endpoint, were -14.2 g (95% CI: -17.4 to -11.1 g) and -12.3 g (95% CI: -16.0 to -8.7 g) in the everolimus and placebo groups (P = 0.99). Corresponding changes in MVO were -4.8 g (95% CI: -6.7 to -2.9 g) and -6.3 g (95% CI: -8.7 to -4.0 g) in the everolimus and placebo groups (P = 0.14). Adverse events did not differ between the study groups. CONCLUSIONS: Among STEMI patients undergoing PCI, early mTOR inhibition with everolimus did not reduce MI size or MVO at 30 days. (CLEVER-ACS [Controlled Level Everolimus in Acute Coronary Syndromes; NCT01529554).

Long-term effects of systematic smoking cessation counselling during acute coronary syndrome, a multicentre before-after study.

TRIAL DESIGN: In the Special Program University Medicine-Acute Coronary Syndromes (SPUM-ACS) observational study (clinical trial registration: NCT01000701), a multicentre before-after clinical trial, we assessed 5-year outcome after acute coronary syndrome, comparing a systematic with an opportunistic smoking cessation counselling phase. METHODS: We studied smokers who were hospitalised for acute coronary syndromes (ACS), and we assessed self-reported smoking cessation, incidence of cardiovascular events and mortality 5 years after hospital discharge. In the observational phase, from August 2009 to October 2010, only smokers who requested smoking cessation counselling received it during hospitalisation. In the interventional phase, from November 2010 to February 2012, hospitalised smokers with ACS were systematically offered intensive smoking cessation counselling including four telephone calls within 2 months of discharge. Because of the before-after design, the care givers were aware of study phase. The objective was to assess whether systematic counselling to every smoker with ACS has an impact on the long-term smoking cessation rate, incidence of cardiovascular events and mortality. Missing data on smoking cessation were analysed with multiple imputation. The study was not powered to assess differences in 5-year smoking cessation rates or cardiovascular outcomes. RESULTS: Overall, 458 smokers with ACS were included at baseline (225 during the intervention phase and 233 during the observation phase). At 5 years, 286 (62.4%) reported their smoking status (140 for the intervention phase and 146 for the observation phase) and 51 (11.1%) had died. There was no statistically significant difference in the abstinence rate between the interventional phase (75/140, 54%), and the observational phase (68/146, 47%), with a risk ratio with multiple imputation adjusted for age, sex, education and ACS type of 1.13 (95% confidence interval [CI] 0.84-1.51, p = 0.4). The 5-year risk of major acute cardiovascular event was similar in the intervention phase as compared with the observational phase. The multivariate adjusted hazard ratio for all-cause mortality was 0.84 (95% CI 0.45-1.60, p = 0.6). CONCLUSIONS: In this controlled long-term interventional study, systematic intensive smoking cessation counselling in all hospitalised smokers with ACS did not increase 5-year smoking cessation rates, nor decrease cardiovascular event recurrence, as compared with opportunistic smoking cessation counselling during hospitalization.

Smoking cessation and depression after acute coronary syndrome.

Smoking and depression are risk factors for acute coronary syndrome (ACS) that often co-exist. We investigated the evolution of depression according to smoking cessation one-year after ACS. Data from 1822 ACS patients of the Swiss multicenter SPUM-ACS cohort study were analyzed over a one-year follow-up. Participants were classified in three groups based on smoking status one-year post-ACS - continuous smokers, smokers who quit within the year, and non-smokers. Depression status at baseline and one-year was assessed with the Center for Epidemiologic Studies Depression scale (CES-D) and antidepressant drug use. A CES-D score ≥ 16 defined depression. A multivariate-adjusted logistic regression model was used to calculate odds ratios (OR) between groups. The study sample mean age was 62.4 years and females represented 20.8%. At baseline, 22.6% were depressed, 40.9% were smokers, and 47.5% of these quit smoking over the year post-ACS. In comparison to depressed continuous smokers, depressed smokers who quit had an adjusted OR 2.59 (95% confidence interval (CI) 1.27-5.25) of going below a CES-D score of 16 or not using antidepressants. New depression at one-year was found in 24.4% of non-depressed smokers who quit, and in 27.1% of non-depressed continuous smokers, with an adjusted OR 0.85 (95% CI 0.55-1.29) of moving to a CES-D score of ≥16 or using antidepressants. In conclusion, smokers with depression at time of ACS who quit smoking improved their depression more frequently compared to continuous smokers. The incidence of new depression among smokers who quit after ACS was similar compared to continuous smokers.

[European guidelines 2021 for the cardiovascular prevention: new concepts]. / Recommandations européennes 2021 pour la prévention cardiovasculaire : nouveautés.

The latest European guidelines for cardiovascular prevention were published in 2021. As compared to the previous 2016 edition, these guidelines include some new concepts. First, the estimation of cardiovascular risk in apparently healthy persons now encompasses for the first time both fatal and nonfatal events, including myocardial infarction and stroke, using the new SCORE2 and SCORE2-OP. Second, the cardiovascular risk thresholds estimated with the scores are now stratified by age. Medical comorbidities play a more important role in risk estimation and preventive treatment. Finally, in the interest of a more personalized management, a step-by-step attitude is proposed to reach therapeutic goals adapted to the patient.

Les dernières recommandations européennes pour la prévention cardiovasculaire ont été publiées en 2021. Elles innovent, avec quelques nouveaux concepts par rapport aux précédentes recommandations de 2016. Premièrement, l'estimation du risque cardiovasculaire à 10 ans chez les patients apparemment en bonne santé englobe pour la première fois les événements mortels et non mortels, incluant l'infarctus et l'AVC, avec les nouveaux SCORE2 (Systemic Coronary Risk Estimation 2) et SCORE2-OP (Older Persons). Deuxièmement, les seuils de risque cardiovasculaire estimés avec les scores sont maintenant stratifiés selon l'âge. Les comorbidités médicales jouent également un rôle plus important dans la décision du traitement préventif. Enfin, dans le souci d'une prise en charge plus personnalisée, une attitude par paliers est proposée pour atteindre des buts thérapeutiques adaptés au patient.

Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS) - A phase II, randomized, double-blind, multi-center, placebo-controlled trial.

BACKGROUND: Activation of inflammatory pathways during acute myocardial infarction contributes to infarct size and left ventricular (LV) remodeling. The present prospective randomized clinical trial was designed to test the efficacy and safety of broad-spectrum anti-inflammatory therapy with a mammalian target of rapamycin (mTOR) inhibitor to reduce infarct size. DESIGN: Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS, clinicaltrials.gov NCT01529554) is a phase II randomized, double-blind, multi-center, placebo-controlled trial on the effects of a 5-day course of oral everolimus on infarct size, LV remodeling, and inflammation in patients with acute ST-elevation myocardial infarction (STEMI). Within 5 days of successful primary percutaneous coronary intervention (pPCI), patients are randomly assigned to everolimus (first 3 days: 7.5 mg every day; days 4 and 5: 5.0 mg every day) or placebo, respectively. The primary efficacy outcome is the change from baseline (defined as 12 hours to 5 days after pPCI) to 30-day follow-up in myocardial infarct size as measured by cardiac magnetic resonance imaging (CMRI). Secondary endpoints comprise corresponding changes in cardiac and inflammatory biomarkers as well as microvascular obstruction and LV volumes assessed by CMRI. Clinical events, laboratory parameters, and blood cell counts are reported as safety endpoints at 30 days. CONCLUSION: The CLEVER-ACS trial tests the hypothesis whether mTOR inhibition using everolimus at the time of an acute STEMI affects LV infarct size following successful pPCI.

Risks and benefits of urinary catheterisation during inpatient diuretic therapy for acute heart failure: a retrospective, non-inferiority, cohort study.

OBJECTIVES: Patients with acute congestive heart failure (HF) regularly undergo urinary catheterisation (UC) at hospital admission. We hypothesised that UC has no clinical benefits with regard to weight loss during inpatient diuretic therapy for acute congestive HF and increases the risk of urinary tract infection (UTI). DESIGN: Retrospective, non-inferiority study. SETTING: Geneva University Hospitals' Department of Medicine, a tertiary centre. PARTICIPANTS: In a cohort of HF patients, those catheterised within 24 hours of diuretic therapy (n=113) were compared with non-catheterised patients (n=346). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was weight loss 48 hours after starting diuretic therapy. Secondary endpoints were time needed to reach target weight, discontinuation of intravenous diuretics and resolution of respiratory failure. Complications included the time to a first UTI, first hospital readmission and death. RESULTS: A total of 48-hour weight loss was not statistically different between groups and the adjusted difference was below the non-inferiority boundary of 1 kg (0.43 kg (95% CI: -0.03 to 0.88) in favour of UC, p<0.01 for non-inferiority). UC was not associated with time to reaching target weight (adjusted HR 1.0; 95% CI: 0.7 to 1.5), discontinuation of intravenous diuretics (aHR 0.9; 95% CI: 0.7 to 1.2) or resolution of respiratory failure (aHR 1.1; 95% CI: 0.5 to 2.4). UC increased the risk of UTI (aHR 2.5; 95% CI: 1.5 to 4.2) but was not associated with hospital readmission (aHR 1.1; 95% CI: 0.8 to 1.4) or 1-year mortality (aHR 1.4; 95% CI: 1.0 to 2.1). CONCLUSION: In this retrospective study, with no obvious hourly diuresis-based diuretic adjustment strategy, weight loss without UC was not inferior to weight loss after UC within 24 hours of initiating diuretic treatment. UC had no impact on clinical improvement and increased the risk of UTI. This evidence, therefore, argues against the systematic use of UC during a diuretic therapy for HF.

Effectiveness, Adherence, and Safety of Evolocumab in a Swiss Multicenter Prospective Observational Study.

INTRODUCTION: The aims of this study were to describe patient characteristics, lipid parameters, lipid-lowering drug use, and safety of patients receiving evolocumab in a real-world clinical setting. METHODS: We conducted a 1-year multicenter observational study of adults using evolocumab with confirmed atherosclerotic cardiovascular disease (CVD) or at high cardiovascular risk, and elevated LDL-C despite maximally tolerated statin doses. An e-health application optionally supported patient management. The primary outcome was change in lipid parameters over time. The secondary outcomes included evolocumab safety. RESULTS: Of 100 participants, 81% had pre-existing CVD, 71% self-reported statin-related muscle symptoms, 44% received statins. All patients received evolocumab, 65% were PCSK9i pre-treated at baseline. PCSK9i-naïve patients achieved a mean LDL-C reduction of 60% within 3 months of evolocumab treatment, which was maintained thereafter; 74% achieved LDL-C < 1.8 mmol/L at least once during observation, 69% attained < 1.4 mmol/L. In PCSK9i pre-treated patients, LDL-C remained stable throughout; 79% and 74% attained < 1.8 mmol/L and < 1.4 mmol/L, respectively, at least once. Goal attainment was higher with any combination of evolocumab, statin, and/or ezetimibe. Overall, 89% self-reported full evolocumab adherence. Treatment-emergent adverse events (TEAE) were reported in 30% of patients, two serious TEAEs occurred in one patient; three patients discontinued evolocumab because of TEAEs. CONCLUSION: In real-world clinical practice, evolocumab was mainly used in patients with statin intolerance and pre-existing CVD. In this population, adherence to evolocumab and low LDL-C levels were maintained over 1 year, with better LDL-C goal achievement in patients using evolocumab in combination with other lipid-lowering drugs. Safety of evolocumab was similar to that documented in randomized controlled trials.