Short- and Long-Term Prognosis of Patients With Takotsubo Syndrome Based on Different Triggers: Importance of the Physical Nature

Background Takotsubo syndrome (TTS) is an acute reversible heart condition initially believed to represent a benign pathology attributable to its self-limiting clinical course; however, little is known about its prognosis based on different triggers. This study compared short- and long-term outcomes between TTS based on different triggers, focusing on various physical triggering events. Methods and Results We analyzed patients with a definitive TTS diagnosis recruited for the Spanish National Registry on TTS (RETAKO [Registry on Takotsubo Syndrome]). Short- and long-term outcomes were compared between different groups according to triggering factors. A total of 939 patients were included. An emotional trigger was detected in 340 patients (36.2%), a physical trigger in 293 patients (31.2%), and none could be identified in 306 patients (32.6%). The main physical triggers observed were infections (30.7%), followed by surgical procedures (22.5%), physical activities (18.4%), episodes of severe hypoxia (18.4%), and neurological events (9.9%). TTS triggered by physical factors showed higher mortality in the short and long term, and within this group, patients whose physical trigger was hypoxia were those who had a worse prognosis, in addition to being triggered by physical factors, including age >70 years, diabetes mellitus, left ventricular eyection fraction <30% and shock on admission, and increased long-term mortality risk. Conclusions TTS triggered by physical factors could present a worse prognosis in terms of mortality. Under the TTS label, there could be as yet undiscovered very different clinical profiles, whose differentiation could lead to individual better management, and therefore the perception of TTS as having a benign prognosis should be generally ruled out

Acute Heart Failure in the 2021 ESC Heart Failure Guidelines: a scientific statement from the Association for Acute CardioVascular Care (ACVC) of the European Society of Cardiology.

The current European Society of Cardiology (ESC) Heart Failure Guidelines are the most comprehensive ESC document covering heart failure to date; however, the section focused on acute heart failure remains relatively too concise. Although several topics are more extensively covered than in previous versions, including some specific therapies, monitoring and disposition in the hospital, and the management of cardiogenic shock, the lack of high-quality evidence in acute, emergency, and critical care scenarios, poses a challenge for providing evidence-based recommendations, in particular when by comparison the data for chronic heart failure is so extensive. The paucity of evidence and specific recommendations for the general approach and management of acute heart failure in the emergency department is particularly relevant, because this is the setting where most acute heart failure patients are initially diagnosed and stabilized. The clinical phenotypes proposed are comprehensive, clinically relevant and with minimal overlap, whilst providing additional opportunity for discussion around respiratory failure and hypoperfusion.F.P. has received research grants from Abbott, Becton Dickenson, Brainbox, Calcimedica, CSL Behring, Cue, Ortho Clinical Diagnostics, Relypsa, Roche, Salix, Siemens. Consultant: Abbott, Astra-Zeneca, Beckman, Bosch, Fast Biomedical, Forrest Devices, Ischemia Care, Dx, Instrument Labs, Janssen, Nabriva, Ortho Clinical Diagnostics, Osler, Relypsa, Roche, Quidel, Salix, Siemens, Upstream and has stock/ownership interests in AseptiScope Inc, Brainbox Inc, Braincheck Inc, Coagulo Inc, Comprehensive Research Associates LLC, Comprehensive Research Management Inc, Emergencies in Medicine LLC, Fast Inc, Forrest Devices, Ischemia DX LLC, Lucia Inc, Prevencio Inc, ScPharma, Trivirum Inc, Upstream Inc. E.P.’ employer has received support from Novartis for consulting work and she has consulted for scPharmaceuticals outside of the submitted work. She has received research support from the NIH (R01HL148439).S

Health Outcome Predictive Evaluation for COVID 19 international registry (HOPE COVID-19), rationale and design

The disease produced by the new coronavirus known as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), named COVID-19 (Coronavirus Disease-2019) has recently been classified as a pandemic by the World Health Organization (WHO). However, scarce clinical data is available and generally limited to the Chinese population due to the first cases were identified in Wuhan (Hubei, China).This article describes the rationale and design of the HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID 19) registry (ClinicalTrials.gov Identifier: NCT04334291). With an ambispective cohort design, eligible patients are those discharged, deceased or alive, from any hospital center with a confirmed diagnosis or a COVID-19 high suspicion. With a current recruitment of more than 7000 cases, in 46 hospitals in 8 countries, since it is not possible to estimate the sample size based on literature reports, the investigators will try to get the maximum numbers of patients possible. The study primary objective is all cause mortality and aims to characterize the clinical profile of patients infected in order to develop a prognostic clinical score allowing, rapid logistic decision making. As secondary objectives, the analysis of other clinical events, the risk-adjusted influence of treatments and previous comorbidities of patients infected with the disease will be performed.The results of HOPE COVID-19 will contribute to a better understanding of this condition. We aim to describe the management of this condition as well as the outcomes in relation to the therapy chosen, in order to gain insight into improving patient care in the coming months. Clinical Trial registration: ClinicalTrials.gov. Unique identifier: NCT04334291

Connetion of early primary perutaneous oronary intervention with mortality and quality of life of patients with myoardial infarction with ST segment elevation

Primena reperfuzione terapije se preporučuje za pacijente sa infarktom miokarda sa ST segment elevacijom (STEMI), a vremenski interval kašnjenje sistema je predloženo kao merilo indeksa kvaliteta pružanja medicinske nege u lečenju pacijenata sa STEMI primarnom perkutanom koronarnom intervencijom (pPCI). Međutim, posmatranje vremena od pojave simptoma do primene pPCI (ukupno ishemijsko vreme (TD)) je relevantnije, jer oštećenje miokarda počinje sa pojavom simptoma. Do sada nije sprovedena slična studija u Srbiji koja bi povezala TD sa lošim ishodima kod pacijenata sa STEMI lečenim pPCI. Cilj: Ova studija je imala za cilj procenu ishoda i kvaliteta života kod pacijenata sa STEMI u odnosu na TD u dugoročnom praćenju. Metode: Analizirali smo 507 pacijenata sa STEMI koji su lečeni primenom pPCI. Pacijenti su klasifikovani prema trajanju TD na pacijente kod kojih je intervencija primenjena u prva četiri sata od početka simptoma i pacijenata kod kojih je intervencija primenjena nakon četiri sata od početka simptoma. Tokom 48-mesečnog praćenja upoređivali smo osnovne karakteristike, kliničke nalaze, ishode i kvalitet života kod ovih pacijenata. Rezultati: Pacijenti sa STEMI kod kojih je pPCI primenjena nakon 240 minuta od početka simptoma imaju značajno veću incidencu dijabetes melitusa i zastupljenost ženskog pola u odnosu na pacijente kod kojih je pPCI primenjena u intervalu kraćem od 240 minuta. U ostalim demografskim, kliničkim i angiografskim varijablama nije bilo razlike. Četvorogodišnja opšta smrtnost u celoj grupi ispitanika je iznosila 18,74% (95 pacijenata), zabeležili smo značajne razlike u stopi smrtnosti između ispitivanih grupa (12,6% naspram 23,3% p = 0,002). U multivarijantnoj analizi nakon prilagođavanja za druge faktore mortaliteta, TD> 240 min. je ostao nezavisni prediktor mortaliteta (OR 2,087 95% CI (1.002-4.345) p = 0,049) tokom praćenja. Osim TD, nezavisni prediktori za smrtnost su bili: dijabetes melitus, starost, trosudovna koronarna bolest, prethodna revaskularizacija i srčana insuficijencija (Killip≥2). Nezavisni prediktori za kvalitet života povezan sa zdravljem su bili starost, pol, dijabetes melitus i arterijska hipertenzija. U našoj studiji TD nije bio povezan sa kvalitetom života. Zaključak: kašnjenje sa priemnom pPCI više od 240 minuta povezano je sa mortalitetom. Smanjenje totalnog ishemijskog vremena je presudno za pacijente sa STEMI lečenim pPCI. Povećani napori u organizaciji zbrinjavanja pacijenata sa STEMI su od suštinskog značaja za smanjenje kašnjenja sa primneom pPCi i povećanja efikasnosti primenjene terapije.Timely reperfusion therapy is recommended for patients with ST segment elevation myocardial infarction(STEMI), and system delay has been proposed as a performance measure in treatment of patients with primary percutaneous coronary intervention (pPCI). However, focusing on the treatment delay (total ischemic time (TD)) is more relevant, since myocardial impairment starts with symptoms onset. No previous studies have demonstrated the association between TD and outcome in patients with STEMI treated with pPCI in Serbia. Objective: This study aimed at evaluating long term outcomes and quality of life in patients with STEMI according to the TD. Methods: We analyzed 507 patients with STEMI who were admitted for pPCI. The patients were classified according to the duration of TD into patients with symptom onset to balloon time less than 240 minutes and the patients who had the pPCI intervention four hours after the symptoms onset. During the 48-month follow up we compared baseline characteristics, clinical findings, outcomes and quality of life among these patients. Results: Patients with STEMI undergoing primary percutaneous coronary intervention with symptom onset to balloon time more than 240 minutes had higher incidence of diabetes mellitus and there were more patients of female sex compared to patients treated earlier. In other baseline and angiographic variables two groups were similar. Four year mortality in entire cohort was 18,74% (95 patients), and we recorded significant differences in mortality between groups (12,6% vs 23,3% p=0,002). In multivariable analysis adjusted for other predictors for mortality, TD>240 min. was independent predictor for mortality (OR 2.087 95%CI(1.002-4.345) p=0,049) during the follow up. Besides treatment delay, independent predictors for mortality were: diabetes mellitus, age, three vessel coronary artery disease, prior revascularization and heart failure (Killip≥2). Independent predictors for HRQoL were age, sex, diabetes mellitus and arterial hypertension. TD was not associated with HRQoL. Conclusion: More than 240 minutes treatment delay was associated with mortality. The reduction of treatment delay is crucial for patients with STEMI treated with pPCI. Joint actions in organization and care of patients with STEMI are essential to increase treatment efficacy and reduce adverse outcomes

Association of Beta-Blockers with Survival on Patients Presenting with ACS Treated with PCI: A Propensity Score Analysis from the BleeMACS Registry

Purpose: The aim was to evaluate prognostic value of beta-blocker (BB) administration in acute coronary syndromes (ACS) patients in the percutaneous coronary intervention (PCI) era. Methods and Results: The BleeMACS project is a multicenter, observational, retrospective registry enrolling patients with ACS worldwide in 15 hospitals. Patients discharged with BB therapy were compared to those discharged without a BB before and after propensity score with matching. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints included in-hospital reinfarction, in-hospital heart failure, 1-year myocardial infarction, 1-year bleeding and 1-year composite of death and recurrent myocardial infarction. After matching, 2935 patients for each group were enrolled. The primary endpoint of 1-year death was significantly lower in the group on BB therapy (4.5 vs 7%, p < 0.05), while only a trend was noted for recurrent acute myocardial infarction (4.5 vs 4.9%, p = 0.54). These results were consistent for patients older than 80 years of age, for ST-elevation myocardial infarction (STEMI) patients, and for those discharged with complete versus incomplete revascularization, but not for non-STEMI/unstable angina patients. Conclusions: BB therapy was related to 1-year lower risk of all-cause mortality, independently from completeness of revascularization, admission diagnosis, age and ejection fraction. Randomized controlled trials for patients treated with PCI for ACS should be performed

Prediction of Post-Discharge Bleeding in Elderly Patients with Acute Coronary Syndromes: Insights from the BleeMACS Registry

Background A poor ability of recommended risk scores for predicting in-hospital bleeding has been reported in elderly patients with acute coronary syndromes (ACS). No study assessed the prediction of post-discharge bleeding in the elderly. The new BleeMACS score (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome), was designed to predict post-discharge bleeding in ACS patients. We aimed to assess the predictive ability of the BleeMACS score in elderly patients. Methods We assessed the incidence and characteristics of severe bleeding after discharge in ACS patients aged ≥ 75 years. Bleeding was defined as any intracranial bleeding or bleeding leading to hospitalization and/or red blood transfusion, occurring within the first year after discharge. We assessed the predictive ability of the BleeMACS score according to age by Fine-Gray proportional hazards regression analysis, calculating receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUC). Results The BleeMACS registry included 15,401 patients of whom 3,376/15,401 (21.9%) were aged ≥ 75 years. Elderly patients were more commonly treated with clopidogrel and less often treated with ticagrelor or prasugrel. Of 3,376 elderly patients, 190 (5.6%) experienced post-discharge bleeding. The incidence of bleeding was moderately higher in elderly patients (hazard ratio [HR], 2.31, 95% confidence interval [CI], 1.92-2.77). The predictive ability of the BleeMACS score was moderately lower in elderly patients (AUC, 0.652 vs. 0.691, p = 0.001). Conclusion Elderly patients with ACS had a significantly higher incidence of post-discharge bleeding. Despite a lower predictive ability in older patients, the BleeMACS score exhibited an acceptable performance in these patients

Current status of NADPH oxidase research in cardiovascular pharmacology

Bruno K Rodi&ntilde;o-Janeiro,1,2 Beatriz Paradela-Dobarro,1 Mar&iacute;a Isabel Casti&ntilde;eiras-Landeira,1 Sergio Raposeiras-Roub&iacute;n,1,3 Jos&eacute; R Gonz&aacute;lez-Juanatey,1,3,4 Ezequiel &Aacute;lvarez1,4 1Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain; 2European Molecular Biology Laboratory, Grenoble, France; 3Cardiology Department, University Clinic Hospital of Santiago de Compostela, Santiago de Compostela, Spain; 4Medicine Department, University of Santiago de Compostela, Santiago de Compostela, Spain Abstract: The implications of reactive oxygen species in cardiovascular disease have been known for some decades. Rationally, therapeutic antioxidant strategies combating oxidative stress have been developed, but the results of clinical trials have not been as good as expected. Therefore, to move forward in the design of new therapeutic strategies for cardiovascular disease based on prevention of production of reactive oxygen species, steps must be taken on two fronts, ie, comprehension of reduction-oxidation signaling pathways and the pathophysiologic roles of reactive oxygen species, and development of new, less toxic, and more selective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors, to clarify both the role of each NADPH oxidase isoform and their utility in clinical practice. In this review, we analyze the value of NADPH oxidase as a therapeutic target for cardiovascular disease and the old and new pharmacologic agents or strategies to prevent NADPH oxidase activity. Some inhibitors and different direct or indirect approaches are available. Regarding direct NADPH oxidase inhibition, the specificity of NADPH oxidase is the focus of current investigations, whereas the chemical structure-activity relationship studies of known inhibitors have provided pharmacophore models with which to search for new molecules. From a general point of view, small-molecule inhibitors are preferred because of their hydrosolubility and oral bioavailability. However, other possibilities are not closed, with peptide inhibitors or monoclonal antibodies against NADPH oxidase isoforms continuing to be under investigation as well as the ongoing search for naturally occurring compounds. Likewise, some different approaches include inhibition of assembly of the NADPH oxidase complex, subcellular translocation, post-transductional modifications, calcium entry/release, electron transfer, and genetic expression. High-throughput screens for any of these activities could provide new inhibitors. All this knowledge and the research presently underway will likely result in development of new drugs for inhibition of NADPH oxidase and application of therapeutic approaches based on their action, for the treatment of cardiovascular disease in the next few years. Keywords: nicotinamide adenine dinucleotide phosphate oxidase, NOX, cardiovascular therapeutic targets, inhibitors, pharmacophore model

Predictive value of advanced glycation end products for the development of post-infarction heart failure

Background Since post-infarction heart failure (HF) determines a great morbidity and mortality, and given the physiopathology implications of advanced glycation end products (AGE) in the genesis of myocardial dysfunction, it was intended to analyze the prognostic value of these molecules in order to predict post-infarction HF development. Methods A prospective clinical study in patients after first acute coronary syndrome was conducted. The follow-up period was consisted in 1 year. In 194 patients consecutively admitted in the coronary unit for myocardial infarct fluorescent AGE levels were measured. The association between glycaemic parameters and the development of post-infarction HF were analyzed in those patients. Finally, we identified the variables with independent predictor value by performing a multivariate analysis of Hazard ratio for Cox regression. Results Eleven out of 194 patients (5.6%) developed HF during follow-up (median: 1.0 years [0.8 - 1.5 years]). Even though basal glucose, fructosamine and glycated haemoglobin were significant predictive factors in the univariate analysis, after being adjusted by confounding variables and AGE they lost their statistical signification. Only AGE (Hazard Ratio 1.016, IC 95%: 1.006-1.026; p<0,001), together with NT-proBNP and the infarct extension were predictors for post-infarction HF development, where AGE levels over the median value 5-fold increased the risk of HF development during follow-up. Conclusions AGE are an independent marker of post-infarction HF development risk.This study was supported in part by the Plan Nacional Español de I+D, 2008–2011 and the Instituto de Salud Carlos III – Subdirección General de Evaluación y Fomento de la Investigación, PI10/01403, cofinanced by ERDF. The Isidro Parga Pondal program of the Xunta de Galicia (Spain) supported the work of E. ÁlvarezS

Frailty, disability and comorbidity: different domains lead to different effects after surgical aortic valve replacement in elderly patients

OBJECTIVES: Frailty syndrome predicts adverse outcomes after surgical aortic valve replacement. However, disability or comorbidity is frequently associated with preoperative frailty evaluation. The effects of these domains on early and late outcomes were analysed. METHODS: A prospective study including patients aged >/=75 years with symptomatic severe aortic stenosis who received aortic valve replacement with or without coronary artery bypass grafting was conducted. We used the Cardiovascular Health Study Frailty Phenotype to assess frailty, the Lawton-Brody index to define disability and the Charlson comorbidity index (CCI) to evaluate comorbidity. RESULTS: Frailty was identified in 57 (31%), dependence in 18 (9.9%) and advanced comorbidity (CCI >/= 4) in 67 (36.6%) of the 183 enrolled patients. Operative mortality (1.6%), transfusion rate and duration of stay increased in patients with CCI >/=4 (P /=75 years is a safe procedure with low mortality rates. Operative outcomes are mainly affected by comorbidities. The main influence of survival occurs throughout the first year, and an improved functional status prevents any progression towards disabilities, which could potentially benefit long-term outcomes. CLINICAL TRIAL REGISTRATION NUMBER: NCT02745314