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Pubblicazioni recenti - cardiovascular
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Brachyury engineers cardiac repair competent stem cells.
Stem Cells Transl Med2020 Oct;():. doi: 10.1002/sctm.20-0193.
Li Mark, Yamada Satsuki, Shi Ao, Singh Raman Deep, Rolland Tyler J, Jeon Ryounghoon, Lopez Natalia, Shelerud Lukas, Terzic Andre, Behfar Atta,
Abstract
To optimize the regenerative proficiency of stem cells, a cardiopoietic protein-based cocktail consisting of multiple growth factors has been developed and advanced into clinical trials for treatment of ischemic heart failure. Streamlining the inductors of cardiopoiesis would address the resource intensive nature of the current stem cell enhancement protocol. To this end, the microencapsulated-modified-mRNA (M RNA) technique was here applied to introduce early cardiogenic genes into human adipose-derived mesenchymal stem cells (AMSCs). A single mesodermal transcription factor, Brachyury, was sufficient to trigger high expression of cardiopoietic markers, Nkx2.5 and Mef2c. Engineered cardiopoietic stem cells (eCP) featured a transcriptome profile distinct from pre-engineered AMSCs. In?vitro, eCP demonstrated protective antioxidant capacity with enhanced superoxide dismutase expression and activity; a vasculogenic secretome driving angiogenic tube formation; and macrophage polarizing immunomodulatory properties. In?vivo, in a murine model of myocardial infarction, intramyocardial delivery of eCP (600?000 cells per heart) improved cardiac performance and protected against decompensated heart failure. Thus, heart repair competent stem cells, armed with antioxidant, vasculogenic, and immunomodulatory traits, are here engineered through a protein-independent single gene manipulation, expanding the available regenerative toolkit.
© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.
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Social deprivation and one-year survival after stroke: a prospective cohort study.
Eur J Neurol2020 Oct;():. doi: 10.1111/ene.14614.
Béjot Yannick, Bourredjem Abderrahmane, Mimeau Emmanuelle, Joux Julien, Lannuzel Annie, Misslin-Tritsch Caroline, Bonithon-Kopp Claire, Rochemont Devi, Nacher Mathieu, Cabie André, Lalanne Mistrih Marie-Laure, Fournel Isabelle, ,
Abstract
BACKGROUND:
Social deprivation may have a deleterious influence on post-stroke outcomes, but available data in the literature are mixed.
AIM:
The aim of this cohort study was to evaluate the impact of social deprivation on one-year survival in patients with first-ever stroke.
METHODS:
Social deprivation was assessed at individual level with the EPICES score, a validated multidimensional questionnaire, in 1312 patients with ischemic stroke (IS), and 228 patients with spontaneous intracerebral hemorrhage (ICH), who were prospectively enrolled in six French study centers. Baseline characteristics including stroke severity and prestroke functional status were collected. Multivariable Cox models were generated to evaluate the associations between social deprivation and survival at 12 months in IS and ICH separately.
RESULTS:
A total of 819 patients (53.2%) were socially deprived (EPICES score?30.17). In IS, mortality at 12 months was higher in deprived than in non-deprived patients (16% versus 11%, p=0.006). In multivariable analyses, there was no association between deprivation and death occurring within the first 90 days following IS (adjusted hazard ratio [aHR]=0.81, 95% CI:0.54-1.22, p=0.32). In contrast, an excess in mortality was observed between 90 days and 12 months in deprived compared with non-deprived patients (aHR=1.97; 95%CI:1.14-3.42, p=0.016). In patients with ICH, mortality at 12 months did not significantly differ according to deprivation status.
CONCLUSIONS:
Social deprivation was associated with delayed mortality in ischemic stroke patients only, and, although the exact underlying mechanisms are still to be identified, our findings suggest that deprived patients in particular may benefit from an optimization of post-stroke care.
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Dyskalemia: a management problem for students.
Fundam Clin Pharmacol2020 Oct;():. doi: 10.1111/fcp.12621.
Senninger Lisa, Abensur Vuillaume Laure, Frimat Luc, Girerd Nicolas, Lamiral Zohra, Rossignol Patrick, Boivin Jean-Marc,
Abstract
BACKGROUND:
Although dyskalemia is common, its management can be problematic for students and general practitioners, especially when it occurs in patients with heart and renal failure. The basic academic knowledge of general medicine students, who have often not yet encountered clinical situations of dyskalemia, remains unclear in this regard.
OBJECTIVES:
The purpose of this study was to evaluate the knowledge and reflexive practices of general medicine students in regard to dyskalemia.
METHODS:
A cross-sectional survey, based on a self-questionnaire, of all of the students enrolled in general medicine studies at the Faculty of Medicine at the University of Nancy (France) at the end of their degree. The students were asked questions pertaining to specific clinical situations. The answers were compared to the information provided in the medical curriculum as well as to the relevant European guidelines.
RESULTS:
We collected 290 of the questionnaires (participation rate: 81.2%). The hyper- and hypo-kalemia thresholds considered pathological (3.5-5.0 mmol/L) were known by 78% and 67% of the students, respectively. The perception of danger in case of severe hypokalemia was underestimated by 62.7% of them. In most cases, the proposed management of hyperkalemia in heart and renal failure did not comply with the relevant guidelines. The students tended to favor permanent discontinuation of the administration of converting enzyme inhibitors (ACE) and/or mineralocorticoid receptor antagonists (MRA) without considering the need for their reintroduction (51.6%). Sodium polystyrene sulfate was frequently seen as an appropriate first-line treatment for hyperkalemia (45%).
CONCLUSIONS:
The knowledge and competence of general medicine students appear to be lacking for hyperkalemia in heart and renal failure, and they are long way from full compliance with the relevant European guidelines. Exposure to complex clinical situations as part of the medical curriculum, therefore, seems essential to improve the way dyskalemia is managed in France.
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Radiographic features and poor prognostic factors of interstitial lung disease with nivolumab for non-small cell lung cancer.
Cancer Sci2020 Oct;():. doi: 10.1111/cas.14710.
Saito Yoshinobu, Sasaki Shinichi, Oikado Katsunori, Tominaga Junya, Sata Masafumi, Sakai Fumikazu, Kato Terufumi, Iwasawa Tae, Kenmotsu Hirotsugu, Kusumoto Masahiko, Baba Tomohisa, Endo Masahiro, Fujiwara Yutaka, Sugiura Hiroaki, Yanagawa Noriyo, Ito Yoshihiko, Sakamoto Takahiko, Ohe Yuichiro, Kuwano Kazuyoshi,
Abstract
Nivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This post-marketing study evaluated the poor prognostic factors of ILD in nivolumab-treated patients with non-small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an Expert Central Review Committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground glass opacity (peritumoral-GGO). Poor prognostic factors were identified by univariate and multivariate Cox regression analysis. Of the 238 patients with nivolumab-induced ILD, 37 died. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia-like (53.4%), faint infiltration pattern/acute hypersensitivity pneumonia-like (20.2%), diffuse alveolar damage (DAD)-like (10.9%), and nonspecific interstitial pneumonia-like (6.3%). The main poor prognostic factors identified were DAD-like pattern (highest hazard ratio: 10.72), ?60 days from start of nivolumab treatment to onset of ILD, pleural effusion before treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal change in C-reactive protein (CRP) levels. Of the 37 deaths due to ILD, 17 had DAD-like radiographic pattern, 3 had peritumoral-GGO, and 5 had a change in radiographic pattern from non-DAD at onset to DAD-like. Patients with NSCLC who develop ILD during nivolumab treatment should be managed carefully if they have poor prognostic factors such as DAD-like radiographic pattern, onset of ILD ?60 days from nivolumab initiation, pleural effusion before nivolumab treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal changes in CRP levels.
This article is protected by copyright. All rights reserved.
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Alopecia and Gray Hair Are Associated with COVID-19 Severity.
Exp Dermatol2020 Oct;():. doi: 10.1111/exd.14220.
Ramos Paulo Müller, Ianhez Mayra, Miot Hélio Amante,
Abstract
Individual vulnerability to severe acute respiratory syndrome due to COVID-19 has been associated with age and some comorbidities, such as hypertension, diabetes, and cardiovascular disease. Men have an increased risk for severe disease; conversely, prepubescent males appear to be protected.
This article is protected by copyright. All rights reserved.
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Integrating neuronal involvement into the immune and genetic paradigm of vitiligo.
Clin Exp Dermatol2020 Oct;():. doi: 10.1111/ced.14490.
Al Abadie M S, Gawkrodger D J,
Abstract
In this review we show how the neuronal theory is relevant to the convergence theory for the mechanism causing vitiligo, especially the segmental type. Neuropetides and neurotransmitters, e.g. neuropeptide-Y and dopamine, can be central to the pathological mechanisms of melanocyte destruction. They link into a bidirectional network connecting cutaneous nerves, the neuro-endocrine axis, and the immune system, and, through their local influence on cutaneous inflammation, to the antigen-specific regulatory T cells and the chemokine ligand type 9 (CXCL9)/ chemokine receptor type 1 (CXCR1) axis that are thought to be the final pathway for melanocyte destruction.
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QTc interval prolongation and life-threatening arrhythmias during hospitalization in patients with COVID-19. Results from a multi-center prospective registry.
Clin Infect Dis2020 Oct;():. doi: ciaa1578.
Santoro Francesco, Monitillo Francesco, Raimondo Pasquale, Lopizzo Agostino, Brindicci Gaetano, Gilio Michele, Musaico Francesco, Mazzola Michele, Vestito Domenico, Di Benedetto Rossella, Abumayyaleh Mohammad, El-Battrawy Ibrahim, Santoro Carmen Rita, Di Martino Luigi Flavio Massimiliano, Akin Ibrahim, De Stefano Giulio, Fiorilli Rosario, Cannone Michele, Saracino Annalisa, Angarano Salvatore, Carbonara Sergio, Grasso Salvatore, Di Biase Luigi, Brunetti Natale Daniele,
Abstract
BACKGROUND:
Prolonged QTc interval and life-threatening arrhythmias (LTA) are potential drug induced complications previously reported with antimalarial, antivirals and antibiotics.
OBJECTIVES:
To evaluate prevalence and predictors of QTc interval prolongation and incidence of LTA during hospitalization for COVID-19 among patients with normal admission QTc.
METHODS:
110 consecutive patients were enrolled in a multicenter international registry. 12-lead ECG was performed at admission, after 7 and 14 days; QTc values were analyzed.
RESULTS:
Fifteen (14%) patients developed a prolonged-QTc (pQT) after 7 days (mean QTc increase 66±20msec, +16%, p<0.001); these patients were older, had higher basal heart rates, higher rates of paroxysmal atrial fibrillation, lower platelet count. QTc increase was inversely proportional to baseline QTc levels and leukocyte count and directly to basal heart rates(p<0.01).At multivariate stepwise analysis including age, male gender, paroxysmal atrial fibrillation, basal QTc values, basal heart rate and dual antiviral therapy, age(OR 1.06, 95% C.I. 1.00-1.13, p<0.05), basal heart rate(OR 1.07, 95% C.I. 1.02-1.13, p<0.01) and dual antiviral therapy(OR 12.46, 95% C.I. 2.09-74.20, p<0.1) were independent predictors of QT-prolongation.Incidence of LTA during hospitalization was 3.6%. One patient experienced cardiac arrest and three non-sustained ventricular tachycardia. LTAs were recorded after a median of 9 days from hospitalization and were associated with 50% of mortality rate.
CONCLUSIONS:
After 7 days of hospitalization, 14% of patients with Covid-19 developed pQTc; age, basal heart rate and dual antiviral therapy were found as independent predictor of pQTc. Life threatening arrhythmias have an incidence of 3.6% and were associated with poor outcome.
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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The sodium-glucose cotransporter 2 inhibitor tofogliflozin prevents diabetic kidney disease progression in type 2 diabetic mice.
FEBS Open Bio2020 Oct;():. doi: 10.1002/2211-5463.13014.
Li Zi, Murakoshi Maki, Ichikawa Saki, Koshida Takeo, Adachi Eri, Suzuki Chigure, Ueda Seiji, Gohda Tomohito, Suzuki Yusuke,
Abstract
Trials on cardiovascular and renal outcomes in patients with type 2 diabetes have consistently demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of diabetic kidney disease (DKD) progression. However, their renal protective mechanisms have yet to be completely understood and the effect on albuminuria reduction in animal models is controversial. Here, we investigated these issues using KK and KK-A mice as a control (CTRL) and as a model for type 2 diabetes (DKD), respectively. KK-A mice were treated with 0.015% tofogliflozin, which is an SGLT2 inhibitor, starting at seven weeks of age for eight weeks. Compared with the CTRL mice, the DKD mice had higher HbA1c levels and albuminuria. Although tofogliflozin treatment significantly lowered HbA1c levels, it did not reverse albuminuria. Tofogliflozin treatment enhanced damage in both the glomerular (i.e., enlarged mesangial area, increased foot process effacement rate, and decreased number of WT-1-positive cells) and tubulointerstitial (increased protein levels of KIM-1 and MCP-1, increased number of macrophages, and abnormal mitochondrial morphology) areas. Our results suggest that tofogliflozin may prevent glomerular and tubulointerstitial damage, partly by ameliorating hyperglycemia, renal inflammation, and abnormal mitochondrial morphology.
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Moderate-to-severe plaque psoriasis, described by PASI ?10%, can be associated with higher cardiovascular risk according to Seven Risk Algorithms: results of a 10-year single-center retrospective study and clinical management of psoriatic patients with cardiovascular risk.
Dermatol Ther2020 Oct;():e14451. doi: 10.1111/dth.14451.
Conforti Claudio, Currado Damiano, Navarini Luca, Retrosi Chiara, Giuffrida Roberta, Zelin Enrico, Afeltra Antonella, di Meo Nicola, Dianzani Caterina, Zalaudek Iris,
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Interactive editing of virtual chordae tendineae for the simulation of the mitral valve in a decision support system.
Int J Comput Assist Radiol Surg2020 Oct;():. doi: 10.1007/s11548-020-02230-y.
Walczak Lars, Tautz Lennart, Neugebauer Mathias, Georgii Joachim, Wamala Isaac, Sündermann Simon, Falk Volkmar, Hennemuth Anja,
Abstract
PURPOSE:
Decision support systems for mitral valve disease are an important step toward personalized surgery planning. A simulation of the mitral valve apparatus is required for decision support. Building a model of the chordae tendineae is an essential component of a mitral valve simulation. Due to image quality and artifacts, the chordae tendineae cannot be reliably detected in medical imaging.
METHODS:
Using the position-based dynamics framework, we are able to realistically simulate the opening and closing of the mitral valve. Here, we present a heuristic method for building an initial chordae model needed for a successful simulation. In addition to the heuristic, we present an interactive editor to refine the chordae model and to further improve pathology reproduction as well as geometric approximation of the closed valve.
RESULTS:
For evaluation, five mitral valves were reconstructed based on image sequences of patients scheduled for mitral valve surgery. We evaluated the approximation of the closed valves using either just the heuristic chordae model or a manually refined model. Using the manually refined models, prolapse was correctly reproduced in four of the five cases compared to two of the five cases when using the heuristic. In addition, using the editor improved the approximation in four cases.
CONCLUSIONS:
Our approach is suitable to create realistically parameterized mitral valve apparatus reconstructions for the simulation of normally and abnormally closing valves in a decision support system.
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Syphilitic aortitis: chronic left coronary ostial occlusion and aortic regurgitation with aortitis.
Gen Thorac Cardiovasc Surg2020 Oct;():. doi: 10.1007/s11748-020-01523-y.
Nomura Ryota, Yamazaki Fumio, Egawa Yuki,
Abstract
Before the discovery of penicillin, tertiary syphilis was the most common cause of thoracic aneurysms, but now cardiovascular syphilis is a clinical rarity in developed countries. We report a case of 69-year-old man who presented with sudden onset breathlessness that worsened insidiously for 2 months. Diagnosis of syphilitic aortitis was confirmed by laboratory findings, contrast computed tomography, echocardiography and coronary angiography. The patient underwent successful coronary artery bypass graft, aortic valve replacement and ascending aortic replacement. A high level of suspicion and awareness is needed for the diagnosis of the now rare disease.
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Non-heart transplant surgical approaches with mitral valve operation and surgical ventricular reconstruction for non-ischaemic dilated cardiomyopathy: a Japanese multicenter study.
Gen Thorac Cardiovasc Surg2020 Oct;():. doi: 10.1007/s11748-020-01512-1.
Cho Yasunori, Wakasa Satoru, Usui Akihiko, Minatoya Kenji, Arai Hirokuni, Yaku Hitoshi, Yamaguchi Atsushi, Komiya Tatsuhiko, Matsumiya Goro, Hamano Kimikazu, Saiki Yoshikatsu, Matsui Yoshiro,
Abstract
OBJECTIVES:
There is uncertainty over the efficacy of additional surgical ventricular reconstruction (SVR) associated with mitral valve operation for non-ischaemic dilated cardiomyopathy (DCM). This study aims to assess mid-term outcomes of these non-heart transplant surgical approaches for DCM.
METHODS:
We reviewed retrospectively 106 patients (median age 64, 44 females) who underwent isolated mitral annular plasty (MAP; n?=?34), mitral valve replacement (MVR; n?=?29), and SVR associated with MAP (SVR?+?MAP; n?=?43) for DCM, in 11 Japanese hospitals. We analysed mid-term outcomes, specifically freedom from cardiac death and cardiac event.
RESULTS:
Hospital deaths occurred in 16 patients (15.1%) and cardiac deaths in 36 patients (34.0%) during the study period of 4.4?±?3.5 years. Freedom from cardiac death at 7 years in patients undergoing MAP, MVR, and SVR?+?MAP were, respectively, 79.1%, 82.6%, and 29.5% (P?
CONCLUSIONS:
This study could not show any benefit of additional SVR, by means of volume reduction, to MAP, because the baseline characteristics were different even after the stratification of DCM grade. MVR can be performed with favorable mid-term outcomes even in patients with advanced DCM, while patients undergoing MAP with/without SVR had more frequent MR recurrence or cardiac events. Interestingly, the right ventricular feature is a predictor of both cardiac death and events, with the TR grade being a predictor of poor mid-term outcomes.
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Ultra-high resolution mapping and ablation of accessory pathway conduction.
J Interv Card Electrophysiol2020 Oct;():. doi: 10.1007/s10840-020-00900-0.
Miyazaki Shinsuke, Ishikawa Eri, Mukai Moe, Aoyama Daisetsu, Nodera Minoru, Hasegawa Kanae, Shiomi Yuichiro, Tama Naoto, Ikeda Hiroyuki, Fukuoka Yoshitomo, Ishida Kentaro, Uzui Hiroyasu, Tada Hiroshi,
Abstract
BACKGROUND:
Detailed mapping studies of accessory pathway (AP) conduction have not been previously performed using ultra-high resolution mapping systems. We sought to evaluate the clinical utility of ultra-high resolution mapping systems and the novel "Lumipoint" algorithm in AP ablation.
METHODS:
This study included 17 patients who underwent AP mapping using minielectrode basket catheters and Rhythmia systems. Ablation was performed with 4-mm irrigated-tip catheters.
RESULTS:
Antegrade and retrograde AP conduction was observed in 6 and 16 patients. Atrial activation map was obtained during orthodromic tachycardia and ventricular pacing in 13 (76.5%) and 14 (82.3%) patients, and the earliest activation area was identical. Ventricular activation maps were created during atrial pacing in 3 patients. All maps showed focal activation patterns on global activation histograms, and the valley on the histogram highlighted the earliest activation area. "Complex activation" features further highlighted limited areas with continuous electrical activity during the time period in the majority. APs were located at the mitral and tricuspid annuli in 15 and 2 patients, and all were successfully eliminated with 3.4?±?0.6 s applications. No patients had recurrences during a median follow-up of 15 [10.5-22.5] months. At successful ablation sites, the local atrial and ventricular electrogram amplitudes and ratio tended to be greater, and fusion or continuous electrical activity between the atrial and ventricular components was more frequently observed on the minielectrode than ablation catheter (17/17 vs. 12/17, p?=?0.005).
CONCLUSIONS:
Ultra-high resolution activation mapping and a novel algorithm facilitated the AP localization. The local electrogram characteristics differed between the minielectrode and ablation catheters.
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Clinical risk predictors in atrial fibrillation patients following successful coronary stenting: ENTRUST-AF PCI sub-analysis.
Clin Res Cardiol2020 Oct;():. doi: 10.1007/s00392-020-01760-4.
Goette Andreas, Eckardt Lars, Valgimigli Marco, Lewalter Thorsten, Laeis Petra, Reimitz Paul-Egbert, Smolnik Rüdiger, Zierhut Wolfgang, Tijssen Jan G, Vranckx Pascal,
Abstract
AIMS:
This subgroup analysis of the ENTRUST-AF PCI trial (ClinicalTrials.gov Identifier: NCT02866175; Date of registration: August 2016) evaluated type of AF, and CHADS-VASc score parameters as predictors for clinical outcome.
METHODS:
Patients were randomly assigned after percutaneous coronary intervention (PCI) to either edoxaban (60 mg/30 mg once daily [OD]; n?=?751) plus a P2Y inhibitor for 12 months or a vitamin K antagonist [VKA] (n?=?755) plus a P2Y inhibitor and aspirin (100 mg OD, for 1-12 months). The primary outcome was a composite of major/clinically relevant non-major bleeding (CRNM) within 12 months. The composite efficacy endpoint consisted of cardiovascular death, stroke, systemic embolic events, myocardial infarction (MI), and definite stent thrombosis.
RESULTS:
Major/CRNM bleeding event rates were 20.7%/year and 25.6%/year with edoxaban and warfarin, respectively (HR [95% CI]: 0.83 [0.654-1.047]). The event rates of composite outcome were 7.26%/year and 6.86%/year, respectively (HR [95% CI]): 1.06 [0.711-1.587]), and of overall net clinical benefit were 12.48%/year and 12.80%/year, respectively (HR [(95% CI]: 0.99 [(0.730; 1.343]). Increasing CHADS-VASc score was associated with increased rates of all outcomes. CHADS-VASc score???5 was a marker for stent thrombosis. Paroxysmal AF was associated with a higher occurrence of MI (4.87% versus 2.01%, p?=?0.0024).
CONCLUSION:
After PCI in AF patients, increasing CHADS-VASc score was associated with increased bleeding rates and CHADS-VASc score (??5) predicted the occurrence of stent thrombosis. Paroxysmal AF was associated with MI. These findings may have important clinical implications in AF patients.
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Elevated high-sensitivity troponin T levels at 1-year follow-up are associated with increased long-term mortality after TAVR.
Clin Res Cardiol2020 Oct;():. doi: 10.1007/s00392-020-01759-x.
Seoudy Hatim, Lambers Moritz, Winkler Vincent, Dudlik Linnea, Freitag-Wolf Sandra, Frank Johanne, Kuhn Christian, Rangrez Ashraf Yusuf, Puehler Thomas, Lutter Georg, Bramlage Peter, Frey Norbert, Frank Derk,
Abstract
BACKGROUND:
Elevated pre-procedural high-sensitivity troponin T (hs-TnT) levels predict adverse outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). It is unknown whether elevated troponin levels still provide prognostic information during follow-up after successful TAVR. We evaluated the long-term implications of elevated hs-TnT levels found at 1-year post-TAVR.
METHODS AND RESULTS:
The study included 349 patients who underwent TAVR for severe AS from 2010-2019 and for whom 1-year hs-TnT levels were available. Any required percutaneous coronary interventions were performed?>?1 week before TAVR. The primary endpoint was survival time starting at 1-year post-TAVR. Optimal hs-TnT cutoff for stratifying risk, identified by ROC analysis, was 39.4 pg/mL. 292 patients had hs-TnT??300 pg/mL, male sex, an eGFR < 60 mL/min/1.73 m and chronic obstructive pulmonary disease as independent risk factors for long-term mortality after TAVR.
CONCLUSIONS:
Elevated hs-TnT concentrations at 1-year after TAVR were associated with a higher long-term mortality.
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Caffeine ingestion alters central hemodynamics following aerobic exercise in middle-aged men.
Eur J Appl Physiol2020 Oct;():. doi: 10.1007/s00421-020-04521-3.
Harber Matthew P, McCurry Allison, Carlini Nicholas, Kistler Brandon, Fleenor Bradley S,
Abstract
PURPOSE:
To examine the acute influence of caffeine on post-exercise central blood pressures, arterial stiffness, and wave reflection properties.
METHODS:
In a double-blind randomized placebo-controlled crossover study design, ten middle-aged males (55?±?5 year) completed two exercise trials after ingestion of caffeine (400 mg) or placebo. Measurements were taken before and 30 min post-ingestion via cuff-based pulse wave analysis (PWA) and carotid-femoral pulse wave velocity (PWV). Participants performed a 40-min cycling bout at 70% HRmax with matched workloads between trials. PWA and PWV were reassessed 30 min post-exercise.
RESULTS:
Prior to exercise, compared to placebo, caffeine increased brachial systolic blood pressure (bSBP) (+?12.3?±?2.4 mmHg; p?=?0.004), brachial diastolic blood pressure (bDBP) (+?7.7?±?0.9 mmHg; p?=?0.011), central systolic blood pressure (cSBP) (+?11.1?±?2.1 mmHg; p?=?0.005) and central diastolic blood pressure (cDBP) (+?7.6?±?1.0 mmHg; p?=?0.012). PWV was higher 30 min after pill ingestion (p?=?0.021 for time) with a trend for a greater increase in caffeine (p?=?0.074 for interaction). bSBP (p?=?0.036) and cSBP (p?=?0.007) were lower after exercise but remained higher (both p?
CONCLUSION:
In healthy and active middle-aged men, pre-exercise caffeine ingestion led to higher central and peripheral systolic blood pressures, PWV and AIx at 30 min post-exercise, indicating an increased left ventricular workload which may have implications for cardiovascular event risk.
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Effects of long-term vitamin D and n-3 fatty acid supplementation on inflammatory and cardiac biomarkers in patients with type 2 diabetes: secondary analyses from a randomised controlled trial.
Diabetologia2020 Oct;():. doi: 10.1007/s00125-020-05300-7.
Limonte Christine P, Zelnick Leila R, Ruzinski John, Hoofnagle Andrew N, Thadhani Ravi, Melamed Michal L, Lee I-Min, Buring Julie E, Sesso Howard D, Manson JoAnn E, de Boer Ian H,
Abstract
AIMS/HYPOTHESIS:
Interventions that reduce inflammation may delay progression of microvascular and macrovascular complications in diabetes. We examined the effects of vitamin D and/or n-3 fatty acid supplementation vs placebo on 5 year changes in serum inflammatory and cardiac biomarkers in adults with type 2 diabetes.
METHODS:
This study reports pre-specified secondary outcomes of the Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease, in which 1312 US adults with type 2 diabetes and without known cardiovascular disease, malignancy, or end-stage kidney disease were randomised using computer-generated random numbers in blocks of eight to vitamin D (2000 IU/day) vs placebo and n-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]; 1 g/day) vs placebo in a 2?×?2 factorial design. Participants, examiners, and researchers assessing outcomes were blinded to intervention assignment. We measured serum IL-6, high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and after 2 and 5 years.
RESULTS:
A total of 333 participants were randomised to vitamin D and placebo n-3 fatty acids, 289 to n-3 fatty acids and placebo vitamin D, 370 to vitamin D and n-3 fatty acids, and 320 to 2 placebos; 989 (75%) and 934 (71%) participants returned blood samples at 2 and 5 years, respectively. Participants had a mean age of 67.6 years (46% women). Overall, baseline geometric means of IL-6, hsCRP and NT-proBNP were 1.2 pg/ml, 1.9 mg/l and 262 ng/l, respectively. After 5 years, mean IL-6 and hsCRP remained within 6% of their baseline values while mean NT-proBNP increased by 55% overall. Compared with placebo, participants assigned to vitamin D had a 1.24-fold greater increase in NT-proBNP over 5 years (95% CI 1.09, 1.41; p?=?0.003), while IL-6 and hsCRP did not have a significant difference in change. Comparing n-3 fatty acids with placebo, there was no significant difference in change in IL-6, hsCRP or NT-proBNP. No heterogeneity was observed in subgroup analyses accounting for baseline eGFR, urine albumin to creatinine ratio, initial biomarker concentration, 25-hydroxyvitamin D level or EPA+DHA index.
CONCLUSIONS/INTERPRETATION:
Among adults with type 2 diabetes, supplementation with vitamin D or n-3 fatty acids did not reduce IL-6, hsCRP or NT-proBNP over 5 years.
TRIAL REGISTRATION:
ClinicalTrials.gov NCT01684722 FUNDING: The study was funded by grant R01DK088762 from the National Institute of Diabetes and Digestive and Kidney Diseases. Graphical abstract.
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Study design, result posting and publication of late-stage cardiovascular trials.
Eur Heart J Qual Care Clin Outcomes2020 Oct;():. doi: qcaa080.
Kapelios Chris J, Naci Huseyin, Vardas Panos E, Mossialos Elias,
Abstract
AIMS:
Pre-registration of study protocols in accessible databases is required for publication of study results in high-impact medical journals. Nonetheless, data on characteristics of clinical trials registered in these databases and their outcome, in terms of result reporting and publication are limited.
METHODS AND RESULTS:
We searched for interventional, late-phase cardiovascular disease (CVD) studies in adults registered in Clinicaltrials.gov. first posted after 1/1/2013 and completed up to 31/12/2018. Data on study design, result reporting and publication were collected, and potential associations with a pre-defined set of explanatory factors were examined.In total, 250 CVD trials were included in the analysis. Of these, 193 (77.2%) were randomized studies, 99 (39.6%) open label designs, and 126 (50.4%) had industry as main sponsor. 179 trials (71.6%) evaluated the effect of drugs and 27 (10.8%) evaluated devices. The most common primary outcomes were non-clinical endpoints (76.0%), with only 17% of studies evaluating clinical endpoints. Industry-funded trials focused on patent-protected drugs and devices more often than non-industry-funded trials (72.0% vs. 30.6%, P?
CONCLUSION:
Among late-stage cardiovascular trials only 1/4 had results posted on clinicaltrials.gov and <50% had results published. Industry sponsors were more likely to invest in research on patent-protected drugs and devices than were non-industry sponsors. Industry-sponsored studies were more likely to have their results posted, but less likely to have their results published in the scientific literature.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: journals.permissions@oup.com.
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Caloric restriction mimetics for the treatment of cardiovascular diseases.
Cardiovasc Res2020 Oct;():. doi: cvaa297.
Sciarretta Sebastiano, Forte Maurizio, Castoldi Francesca, Frati Giacomo, Versaci Francesco, Sadoshima Junichi, Kroemer Guido, Maiuri Maria Chiara,
Abstract
Caloric restriction mimetics (CRMs) are emerging as potential therapeutic agents for the treatment of cardiovascular diseases. CRMs include natural and synthetic compounds able to inhibit protein acetyltransferases, to interfere with acetyl coenzyme A biosynthesis or to activate (de)acetyltransferase proteins. These modifications mimic the effects of caloric restriction, which is associated with the activation of autophagy. Previous evidence demonstrated the ability of CRMs to ameliorate cardiac function and reduce cardiac hypertrophy and maladaptive remodeling in animal models of aging, mechanical overload, chronic myocardial ischemia, as well as in genetic and metabolic cardiomyopathies. In addition, CRMs were found to reduce acute ischemia-reperfusion injury. In many cases, these beneficial effects of CRMs appeared to be mediated by autophagy activation. In the present review, we discuss the relevant literature about the role of different CRMs in animal models of cardiac diseases, emphasizing the molecular mechanisms underlying the beneficial effects of these compounds and their potential future clinical application.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: journals.permissions@oup.com.
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Atrial nitroso-redox balance and refractoriness following on-pump cardiac surgery: A randomised trial of atorvastatin.
Cardiovasc Res2020 Oct;():. doi: cvaa302.
Jayaram Raja, Jones Michael, Reilly Svetlana, Crabtree Mark J, Pal Nikhil, Goodfellow Nicola, Nahar Keshav, Simon Jillian, Carnicer Ricardo, DeSilva Ravi, Ratnatunga Chandana, Petrou Mario, Sayeed Rana, Roalfe Andrea, Channon Keith M, Bashir Yaver, Betts Timothy, Hill Michael, Casadei Barbara,
Abstract
AIMS:
Systemic inflammation and increased activity of atrial NOX2-containing NADPH oxidases have been associated with the new onset of atrial fibrillation (AF) after cardiac surgery. In addition to lowering LDL-cholesterol, statins exert rapid anti-inflammatory and antioxidant effects, the clinical significance of which remains controversial.
METHODS AND RESULTS:
We first assessed the impact of cardiac surgery and cardiopulmonary bypass (CPB) on atrial nitroso-redox balance by measuring NO synthase (NOS) and GTP Cyclohydrolase -1 (GCH-1) activity, biopterin content, and superoxide production in paired samples of the right atrial appendage obtained before (PRE) and after CPB and reperfusion (POST) in 116 patients. The effect of perioperative treatment with atorvastatin (80?mg once daily) on these parameters, blood biomarkers and the postoperative atrial effective refractory period (AERP) was then evaluated in a randomized, double-blind, placebo-controlled study in 80 patients undergoing cardiac surgery on CPB.CPB and reperfusion led to a significant increase in atrial superoxide production (74% CI, 71-76%, n?=?46 paired samples, P?
CONCLUSIONS:
Perioperative statin therapy prevents post-reperfusion atrial nitroso-redox imbalance in patients undergoing on-pump cardiac surgery but has no significant impact on postoperative atrial refractoriness, perioperative myocardial injury, or markers of postoperative LV function.Clinical Trial Registration information: https://clinicaltrials.gov/ct2/show/NCT01780740.
TRANSLATIONAL PERSPECTIVE:
Increased atrial ROS production is associated with both incident and prevalent AF, with experimental findings suggesting it may have a causal role in AF induction and AF-induced electrical remodelling. Statin therapy causes a reduction in myocardial and vascular ROS production and as such it may prevent the new onset of AF after cardiac surgery. In patients undergoing on-pump cardiac surgery, we show that perioperative administration of statins prevents myocardial nitroso-redox imbalance after reperfusion without affecting atrial refractoriness or perioperative myocardial injury. These findings suggest that targeting myocardial nitroso-redox imbalance would be unlikely to prevent postoperative complications in patients undergoing on-pump cardiac surgery.
© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.
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