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1.
Eur J Heart Fail ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33136300

RESUMO

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and reduces all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect. This joint position statement from three ESC Associations, HFA, EHRA and EACVI focuses on optimized implementation of CRT. We offer theoretical and practical strategies to achieve more comprehensive CRT referral and post-procedural care by focusing on four actionable domains; (I) overcoming CRT under-utilization, (II) better understanding of pre-implant characteristics, (III) abandoning the term 'non-response' and replacing this by the concept of disease modification, and (IV) implementing a dedicated post-implant CRT care pathway.

2.
Atherosclerosis ; 314: 58-62, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33161318

RESUMO

Coronavirus disease 2019 (COVID-19) increases the risk of several non-pulmonary complications such as acute myocardial injury, renal failure or thromboembolic events. A possible unifying explanation for these phenomena may be the presence of profound endothelial dysfunction and injury. This review provides an overview on the association of endothelial dysfunction with COVID-19 and its therapeutic implications. Endothelial dysfunction is a common feature of the key comorbidities that increase risk for severe COVID-19 such as hypertension, obesity, diabetes mellitus, coronary artery disease or heart failure. Preliminary studies indicate that vascular endothelial cells can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and evidence of widespread endothelial injury and inflammation is found in advanced cases of COVID-19. Prior evidence has established the crucial role of endothelial cells in maintaining and regulating vascular homeostasis and blood coagulation. Aggravation of endothelial dysfunction in COVID-19 may therefore impair organ perfusion and cause a procoagulatory state resulting in both macro- and microvascular thrombotic events. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and statins are known to improve endothelial dysfunction. Data from smaller observational studies and other viral infections suggests a possible beneficial effect in COVID-19. Other treatments that are currently under investigation for COVID-19 may also act by improving endothelial dysfunction in patients. Focusing therapies on preventing and improving endothelial dysfunction could improve outcomes in COVID-19. Several clinical trials are currently underway to explore this concept.

3.
Lancet ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33197395

RESUMO

BACKGROUND: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. METHODS: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 µg/L, or 100-299 µg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed. FINDINGS: Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0·79, 95% CI 0·62-1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64-1·00, p=0·050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0·96, 95% CI 0·70-1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58-0·94, p=0·013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66-0·98, p=0·030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47-0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group. INTERPRETATION: In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death. FUNDING: Vifor Pharma.

4.
J Pathol Clin Res ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33185036

RESUMO

Similar to the influenza A pandemic in 1918/1919, the new Coronavirus disease 2019 (COVID-19) has spread globally. The causes of death in COVID-19 are frequently compared to a seasonal influenza outbreak. Complete COVID-19 autopsy studies were almost non-existent in the first months of the outbreak and are still rare with respect to the number of deaths. It has been recently reported that capillary microthrombi are significantly more prevalent in patients with COVID-19 than in patients with influenza A. To date, the contribution of macrothrombi, i.e. visible thrombi in pulmonary arteries, to the death of patients with influenza A in comparison to COVID-19 remains unaddressed. Here, we report autopsy findings in 411 patients who died from the 'Spanish' influenza A pandemic between May 1918 and April 1919 at the University Hospital Zurich, Switzerland. We compare these results with influenza A autopsies from 2009 to 2020, other influenza A autopsy series and all COVID-19 autopsies published to date. No descriptions of any macroscopic thromboembolic events were mentioned in influenza A autopsy reports. In 75 published COVID-19 autopsies, pulmonary artery thrombosis/embolism was reported in 36%. The direct comparison of macroscopic autopsy findings suggests a significantly greater degree of grossly visible pulmonary macrothrombi in patients with COVID-19 in comparison to influenza A autopsies even though most patients received empiric thromboprophylaxis. This is consistent with the concept of a SARS-related de novo coagulopathy with generalised in situ clot formation, which could explain the high incidence of pulmonary thrombosis/embolism with or without underlying deep vein thrombosis and in the absence of a history of venous thromboembolic events.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33232181

RESUMO

Background - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy, which is associated with life-threatening ventricular arrhythmias. Approximately 60% of patients carry a putative disease-causing genetic variant, but interpretation of genetic test results can be challenging. The aims of this study were to systematically reclassify genetic variants in patients with ARVC and to assess the impact on ARVC diagnosis. Methods - This study included patients from the Multicenter Zurich ARVC Registry who hosted a genetic variant deemed to be associated with the disease. Reclassification of pathogenicity was performed according to the modified 2015 American College of Medical Genetics (ACMG) criteria. ARVC diagnosis (categories: definite, borderline, possible) based on the 2010 Task Force Criteria (TFC) was reclassified after genetic re-adjudication. Results - In 79 patients bearing 80 unique genetic variants, n=47 (58.8%) genetic variants were reclassified, and reclassification was judged to be clinically relevant in n=33 (41.3%). Variants in plakophilin-2 (PKP2) were shown to reclassify less frequently as compared to other genes (PKP2, n=1, 8.3%; desmosomal non-PKP2, n=20, 66.7%; non-desmosomal, n=26, 68.4%) (p=0.001 for overall comparison; PKP2 vs desmosomal non-PKP2, p=0.001; PKP2 vs non-desmosomal, p< 0.001). Genetic reclassification impacted ARVC diagnosis. Eight patients (10.1%) were downgraded from definite to borderline/possible disease at the time of initial genetic testing as well as last follow-up, respectively. Separate genetic reclassification in family members led to downgrading of n=5 (38.5%) of variants. Conclusions - Given that approximately half of genetic variants were reclassified, with 10.1% of patients losing their definite disease status, accurate determination of variant pathogenicity is of utmost importance in the diagnosis of ARVC.

6.
Infect Control Hosp Epidemiol ; : 1-6, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33239124

RESUMO

OBJECTIVE: To assess influenza symptoms, adherence to mask use recommendations, absenteesm and presenteeism in acute care healthcare workers (HCWs) during influenza epidemics. METHODS: The TransFLUas influenza transmission study in acute healthcare prospectively followed HCWs prospectively over 2 consecutive influenza seasons. Symptom diaries asking for respiratory symptoms and adherence with mask use recommendations were recorded on a daily basis, and study participants provided midturbinate nasal swabs for influenza testing. RESULTS: In total, 152 HCWs (65.8% nurses and 13.2% physicians) were included: 89.1% of study participants reported at least 1 influenza symptom during their study season and 77.8% suffered from respiratory symptoms. Also, 28.3% of HCW missed at least 1 working day during the study period: 82.6% of these days were missed because of symptoms of influenza illness. Of all participating HCWs, 67.9% worked with symptoms of influenza infection on 8.8% of study days. On 0.3% of study days, symptomatic HCWs were shedding influenza virus while at work. Among HCWs with respiratory symptoms, 74.1% adhered to the policy to wear a mask at work on 59.1% of days with respiratory symptoms. CONCLUSIONS: Respiratory disease is frequent among HCWs and imposes a significant economic burden on hospitals due to the number of working days lost. Presenteesm with respiratory illness, including influenza, is also frequent and poses a risk for patients and staff. TRIAL REGISTRATION: NCT02478905 (clinicaltrials.gov).

7.
Sci Rep ; 10(1): 20537, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239695

RESUMO

Cardiac magnetic resonance (CMR) imaging has become an important technique for non-invasive diagnosis of takotsubo syndrome (TTS). The long-term prognostic value of CMR imaging in TTS has not been fully elucidated yet. This study sought to evaluate the prognostic value of texture analysis (TA) based on CMR images in patients with TTS using machine learning. In this multicenter study (InterTAK Registry), we investigated CMR imaging data of 58 patients (56 women, mean age 68 ± 12 years) with TTS. CMR imaging was performed in the acute to subacute phase (median time after symptom onset 4 days) of TTS. TA of the left ventricle was performed using free-hand regions-of-interest in short axis late gadolinium-enhanced and on T2-weighted (T2w) images. A total of 608 TA features adding the parameters age, gender, and body mass index were included. Dimension reduction was performed removing TA features with poor intra-class correlation coefficients (ICC ≤ 0.6) and those being redundant (correlation matrix with Pearson correlation coefficient r > 0.8). Five common machine-learning classifiers (artificial neural network Multilayer Perceptron, decision tree J48, NaïveBayes, RandomForest, and Sequential Minimal Optimization) with tenfold cross-validation were applied to assess 5-year outcome including major adverse cardiac and cerebrovascular events (MACCE). Dimension reduction yielded 10 TA features carrying prognostic information, which were all based on T2w images. The NaïveBayes machine learning classifier showed overall best performance with a sensitivity of 82.9% (confidence interval (CI) 80-86.2), specificity of 83.7% (CI 75.7-92), and an area-under-the receiver operating characteristics curve of 0.88 (CI 0.83-0.92). This proof-of-principle study is the first to identify unique T2w-derived TA features that predict long-term outcome in patients with TTS. These features might serve as imaging prognostic biomarkers in TTS patients.

8.
Eur J Heart Fail ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33094495

RESUMO

The co-occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre-clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time.

9.
Eur J Heart Fail ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068051

RESUMO

The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) has recently issued a position paper on the role of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF). The present document provides an update of the position paper, based of new clinical trial evidence. Accordingly, the following recommendations are given: • Canagliflozin, dapagliflozin empagliflozin, or ertugliflozin have consistently demonstrated to be effective for the prevention of HF hospitalization in patients with type 2 diabetes mellitus and established cardiovascular disease or at high cardiovascular risk. The specifically listed agents are recommended. • Dapagliflozin or empagliflozin are recommended to reduce the combined risk of HF hospitalization and cardiovascular death in symptomatic patients with HF and reduced ejection fraction, already receiving guideline-directed medical therapy, regardless of the presence of type 2 diabetes mellitus.

10.
Am J Med ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33010226

RESUMO

PURPOSE: We evaluated whether the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic was associated with changes in the pattern of acute cardiovascular admissions across European centers. METHODS: We set-up a multicenter, multinational, pan-European observational registry in 15 centers from 12 countries. All consecutive acute admissions to emergency departments and cardiology departments throughout a 1-month period during the COVID-19 outbreak were compared with an equivalent 1-month period in 2019. The acute admissions to cardiology departments were classified into 5 major categories: acute coronary syndrome, acute heart failure, arrhythmia, pulmonary embolism, and other. RESULTS: Data from 54,331 patients were collected and analyzed. Nine centers provided data on acute admissions to emergency departments comprising 50,384 patients: 20,226 in 2020 compared with 30,158 in 2019 (incidence rate ratio [IRR] with 95% confidence interval [95%CI]: 0.66 [0.58-0.76]). The risk of death at the emergency departments was higher in 2020 compared to 2019 (odds ratio [OR] with 95% CI: 4.1 [3.0-5.8], P < 0.0001). All 15 centers provided data on acute cardiology departments admissions: 3007 patients in 2020 and 4452 in 2019; IRR (95% CI): 0.68 (0.64-0.71). In 2020, there were fewer admissions with IRR (95% CI): acute coronary syndrome: 0.68 (0.63-0.73); acute heart failure: 0.65 (0.58-0.74); arrhythmia: 0.66 (0.60-0.72); and other: 0.68(0.62-0.76). We found a relatively higher percentage of pulmonary embolism admissions in 2020: odds ratio (95% CI): 1.5 (1.1-2.1), P = 0.02. Among patients with acute coronary syndrome, there were fewer admissions with unstable angina: 0.79 (0.66-0.94); non-ST segment elevation myocardial infarction: 0.56 (0.50-0.64); and ST-segment elevation myocardial infarction: 0.78 (0.68-0.89). CONCLUSION: In the European centers during the COVID-19 outbreak, there were fewer acute cardiovascular admissions. Also, fewer patients were admitted to the emergency departments with 4 times higher death risk at the emergency departments.

11.
Eur J Heart Fail ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006257

RESUMO

Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research is discussed.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32882101

RESUMO

The clinical benefits of renal denervation are still under discussion, since randomized controlled clinical studies have provided inconsistent results. The present retrospective study examined the clinical effects of renal denervation with focus on office blood pressure, heart rate, and changes in renal function. Patients with treatment-resistant hypertension (blood pressure ≥ 140/90 mm Hg in spite of 3 antihypertensive drugs including a diuretic) underwent renal denervation at the University Hospital of Zurich, Switzerland and were followed up until 36 months. Renal denervation was performed using 3 different renal denervation systems. The primary outcome consisted of change in office blood pressure, heart rate, and plasma creatinine at 1, 6, 12, 24, and 36 months after renal denervation. 58 patients underwent renal denervation between August 2010 and December 2017. After exclusion, 50 patients were included in the analyses. At 36 months, the mean office systolic and diastolic blood pressure change was -26.4/-8.8 mm Hg (95% CI: -34.6 to -18.2/-13.5 to -4.2 mm Hg; P < .001 for both). Office heart rate showed no significant change during follow-up (P = .361). Plasma creatinine increased from 90.6 µmol/L (95% CI: 82.1 to 99.0 µmol/L) at baseline to 102.1 µmol/L (95% CI: 95.8 to 108.3 µmol/L) at 36 months (P = .007). No major adverse events occurred. Renal denervation is a safe and effective procedure for patients with treatment-resistant hypertension with a clinically significant antihypertensive effect. Further randomized trials are needed to determine the specific context within which renal denervation should be considered a therapeutic option in antihypertensive care.

13.
Eur J Heart Fail ; 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32892431

RESUMO

The Heart Failure Association of the European Society of Cardiology has published a previous position paper and various guidelines over the past decade recognizing the value of palliative care for those affected by this burdensome condition. Integrating palliative care into evidence-based heart failure management remains challenging for many professionals, as it includes the identification of palliative care needs, symptom control, adjustment of drug and device therapy, advance care planning, family and informal caregiver support, and trying to ensure a 'good death'. This new position paper aims to provide day-to-day practical clinical guidance on these topics, supporting the coordinated provision of palliation strategies as goals of care fluctuate along the heart failure disease trajectory. The specific components of palliative care for symptom alleviation, spiritual and psychosocial support, and the appropriate modification of guideline-directed treatment protocols, including drug deprescription and device deactivation, are described for the chronic, crisis and terminal phases of heart failure.

14.
Cardiovasc Res ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32931562

RESUMO

AIMS: Arterial thrombosis as a result of plaque rupture or erosion is a key event in acute cardiovascular events. Sirtuin 5 (SIRT5) belongs to the lifespan-regulating sirtuin superfamily and has been implicated in acute ischemic stroke and cardiac hypertrophy. This project aims at investigating the role of SIRT5 in arterial thrombus formation. METHODS AND RESULTS: Sirt5 transgenic (Sirt5Tg/0) as well as knock-out (Sirt5-/-) mice underwent photochemically-induced carotid endothelial injury to trigger arterial thrombosis. Primary human aortic endothelial cells (HAECs) treated with SIRT5 silencing-RNA (si-SIRT5) as well as peripheral blood mononuclear cells (PBMCs) from acute coronary syndrome (ACS) patients and non-ACS controls (case-control study, total n = 171) were used to increase the translational relevance of our data. Compared to WT controls, Sirt5Tg/0 mice displayed accelerated arterial thrombus formation following endothelial-specific damage. Conversely, in Sirt5-/-mice arterial thrombosis was blunted. Platelet function was unaltered, as assessed by ex vivo collagen-induced aggregometry. Similarly, activation of the coagulation cascade as assessed by vascular and plasma tissue factor (TF) and TF pathway inhibitor (TFPI) expression was unaltered. Increased thrombus embolization episodes and circulating D-dimer levels suggested augmented activation of the fibrinolytic system in Sirt5-/- mice. Accordingly, Sirt5-/- mice showed reduced plasma and vascular expression of the fibrinolysis inhibitor plasminogen activator inhibitor (PAI)-1. In HAECs, SIRT5-silencing inhibited PAI-1 gene and protein expression in response to TNF-α. This effect was mediated by increased AMPK activation and reduced phosphorylation of the MAP kinase ERK 1/2, but not JNK and p38 as shown both in vivo and in vitro. Lastly, both PAI-1 and SIRT5 gene expression are increased in ACS patients compared to non-ACS controls after adjustment for cardiovascular risk factors, while PAI-1 expression increased across tertiles of SIRT5. CONCLUSIONS: SIRT5 promotes arterial thrombosis by modulating fibrinolysis through endothelial PAI-1 expression. Hence, SIRT5 may be an interesting therapeutic target in the context of atherothrombotic events. TRANSLATIONAL PERSPECTIVES: This study illustrates a novel role for Sirtuin 5 in arterial thrombosis by regulating fibrinolysis through plasminogen activator inhibitor 1 (PAI-1). These results shed new light onto the pathophysiology of arterial thrombus formation which underlies most of the acute atherosclerotic complications. Also, they further affirm the intrinsic relationship between lifespan regulating genes, vascular dysfunction and age-related cardiovascular disease, thus indicating these genes as potential targets for cardiovascular prevention and therapy. Further studies will be needed to assess the predictive ability of SIRT5 in patients with acute cardiovascular or cerebrovascular events. Also, the design of specific SIRT5 inhibitors will allow trials aiming at investigating the efficacy of SIRT5 blockage in the clinical setting.

15.
Am Heart J ; 228: 98-108, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32871329

RESUMO

About half of patients with acute ST-segment elevation myocardial infarction (STEMI) present with multivessel coronary artery disease (MVD). Recent evidence supports complete revascularization in these patients. However, optimal timing of non-culprit lesion revascularization in STEMI patients is unknown because dedicated randomized trials on this topic are lacking. STUDY DESIGN: The MULTISTARS AMI trial is a prospective, international, multicenter, randomized, two-arm, open-label study planning to enroll at least 840 patients. It is designed to investigate whether immediate complete revascularization is non-inferior to staged (within 19-45 days) complete revascularization in patients in stable hemodynamic conditions presenting with STEMI and MVD and undergoing primary percutaneous coronary intervention (PCI). After successful primary PCI of the culprit artery, patients are randomized in a 1:1 ratio to immediate or staged complete revascularization. The primary endpoint is a composite of all-cause death, non-fatal myocardial infarction, ischemia-driven revascularization, hospitalization for heart failure, and stroke at 1 year. CONCLUSIONS: The MULTISTARS AMI trial tests the hypothesis that immediate complete revascularization is non-inferior to staged complete revascularization in stable patients with STEMI and MVD.


Assuntos
Vasos Coronários , Intervenção Coronária Percutânea , Complicações Pós-Operatórias , Infarto do Miocárdio com Supradesnível do Segmento ST , Tempo para o Tratamento/normas , Angiografia Coronária/métodos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Índice de Gravidade de Doença
17.
J Clin Med ; 9(9)2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32825201

RESUMO

AIMS: The diagnostic approach to idiopathic giant-cell myocarditis (IGCM) is based on identifying various patterns of inflammatory cell infiltration and multinucleated giant cells (GCs) in histologic sections taken from endomyocardial biopsies (EMBs). The sampling error for detecting focally located GCs by histopathology is high, however. The aim of this study was to demonstrate the feasibility of gene profiling as a new diagnostic method in clinical practice, namely in a large cohort of patients suffering from acute cardiac decompensation. Methods and Results: In this retrospective multicenter study, EMBs taken from n = 427 patients with clinically acute cardiac decompensation and suspected acute myocarditis were screened (mean age: 47.03 ± 15.69 years). In each patient, the EMBs were analyzed on the basis of histology, immunohistology, molecular virology, and gene-expression profiling. Out of the total of n = 427 patient samples examined, GCs could be detected in 26 cases (6.1%) by histology. An established myocardial gene profile consisting of 27 genes was revealed; this was narrowed down to a specified profile of five genes (CPT1, CCL20, CCR5, CCR6, TLR8) which serve to identify histologically proven IGCM with high specificity in 25 of the 26 patients (96.2%). Once this newly established profiling approach was applied to the remaining patient samples, an additional n = 31 patients (7.3%) could be identified as having IGCM without any histologic proof of myocardial GCs. In a subgroup analysis, patients diagnosed with IGCM using this gene profiling respond in a similar fashion to immunosuppressive therapy as patients diagnosed with IGCM by conventional histology alone. Conclusions: Myocardial gene-expression profiling is a promising new method in clinical practice, one which can predict IGCM even in the absence of any direct histologic proof of GCs in EMB sections. Gene profiling is of great clinical relevance in terms of a) overcoming the sampling error associated with purely histologic examinations and b) monitoring the effectiveness of therapy.

19.
Eur J Heart Fail ; 22(9): 1495-1503, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32618086

RESUMO

Heart failure (HF) is common and associated with a poor prognosis, despite advances in treatment. Over the last decade cardiovascular outcome trials with sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus have demonstrated beneficial effects for three SGLT2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) in reducing hospitalisations for HF. More recently, dapagliflozin reduced the risk of worsening HF or death from cardiovascular causes in patients with chronic HF with reduced left ventricular ejection fraction, with or without type 2 diabetes mellitus. A number of additional trials in HF patients with reduced and/or preserved left ventricular ejection fraction are ongoing and/or about to be reported. The present position paper summarises recent clinical trial evidence and discusses the role of SGLT2 inhibitors in the treatment of HF, pending the results of ongoing trials in different populations of patients with HF.

20.
ESC Heart Fail ; 7(5): 2098-2112, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32618139

RESUMO

AIMS: In hospitalized patients with a clinical diagnosis of acute heart failure (HF) with preserved ejection fraction (HFpEF), the aims of this study were (i) to assess the proportion meeting the 2016 European Society of Cardiology (ESC) HFpEF criteria and (ii) to compare patients with restrictive/pseudonormal mitral inflow pattern (MIP) vs. patients with MIP other than restrictive/pseudonormal. METHODS AND RESULTS: We included hospitalized participants of the ESC-Heart Failure Association (HFA) EURObservational Research Programme (EORP) HF Long-Term Registry who had echocardiogram with ejection fraction (EF) ≥ 50% during index hospitalization. As no data on e', E/e' and left ventricular (LV) mass index were gathered in the registry, the 2016 ESC HFpEF definition was modified as follows: elevated B-type natriuretic peptide (BNP) (≥100 pg/mL for acute HF) and/or N-terminal pro-BNP (≥300 pg/mL) and at least one of the echocardiographic criteria: (i) presence of LV hypertrophy (yes/no), (ii) left atrial volume index (LAVI) of >34 mL/m2 ), or (iii) restrictive/pseudonormal MIP. Next, all patients were divided into four groups: (i) patients with restrictive/pseudonormal MIP on echocardiography [i.e. with presumably elevated left atrial (LA) pressure], (ii) patients with MIP other than restrictive/pseudonormal (i.e. with presumably normal LA pressure), (iii) atrial fibrillation (AF) group, and (iv) 'grey area' (no consistent description of MIP despite no report of AF). Of 6365 hospitalized patients, 1848 (29%) had EF ≥ 50%. Natriuretic peptides were assessed in 28%, LV hypertrophy in 92%, LAVI in 13%, and MIP in 67%. The 2016 ESC HFpEF criteria could be assessed in 27% of the 1848 patients and, if assessed, were met in 52%. Of the 1848 patients, 19% had restrictive/pseudonormal MIP, 43% had MIP other than restrictive/pseudonormal, 18% had AF and 20% were grey area. There were no differences in long-term all-cause or cardiovascular mortality, or all-cause hospitalizations or HF rehospitalizations between the four groups. Despite fewer non-cardiac comorbidities reported at baseline, patients with MIP other than restrictive/pseudonormal (i.e. with presumably normal LA pressure) had more non-cardiovascular (14.0 vs. 6.7 per 100 patient-years, P < 0.001) and cardiovascular non-HF (13.2 vs. 8.0 per 100 patient-years, P = 0.016) hospitalizations in long-term follow-up than patients with restrictive/pseudonormal MIP. CONCLUSIONS: Acute HFpEF diagnosis could be assessed (based on the 2016 ESC criteria) in only a quarter of patients and confirmed in half of these. When assessed, only one in three patients had restrictive/pseudonormal MIP suggestive of elevated LA pressure. Patients with MIP other than restrictive/pseudonormal (suggestive of normal LA pressure) could have been misdiagnosed with acute HFpEF or had echocardiography performed after normalization of LA pressure. They were more often hospitalized for non-HF reasons during follow-up. Symptoms suggestive of acute HFpEF may in some patients represent non-HF comorbidities.

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