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Pubblicazioni recenti - cardiac disease
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Anticardiolipin antibody and anti-?2 glycoprotein I antibody are potential risk markers of ischaemic stroke in Chinese adults.
Rheumatology (Oxford)2019 Nov;():. doi: kez551.
Dong Shengyong, Pei Bin, Xie Wuxiang, Wang Jing, Zeng Qiang,
Abstract
OBJECTIVES:
aCL and anti-?2 glycoprotein I antibody (a?2GPI) are autoantibodies associated with thromboembolic diseases. Here we investigated whether they are correlated with ischaemic cardiovascular disease in a Chinese population.
METHODS:
Serum total aCL and a?2GPI isotypes (IgA, IgG or IgM, separately) were measured in 11 015 Chinese adults. Differences of antibody level between disease and non-disease groups were examined by t-test. The correlation between antibody and ischaemic cardiovascular disease was determined by logistic regression analysis. Performance of risk prediction models employed aCL or a?2GPI isotypes was evaluated by C statistic, net reclassification improvement index and integrated discrimination improvement.
RESULTS:
Total aCL and a?2GPI isotypes maintained low levels and increased with increasing age except total aCL and a?2GPI IgG in participants older than 70?years. When distinguishing ischaemic cardiovascular disease by coronary heart disease (CHD) and ischaemic stroke, the stroke group had higher levels of aCL and a?2GPI isotypes than the non-stroke group, while the CHD group only had a slightly higher a?2GPI IgG than non-CHD groups. aCL and a?2GPI were positively correlated with stroke but not with CHD, and improved the performance of conventional risk factors for stroke risk prediction, with C statistic from 0.769 (95% CI 0.744, 0.793) to 0.777 (95% CI 0.754, 0.800) (a?2GPI IgG, P?=?0.0091), and 0.778 (95% CI 0.754, 0.801) (a?2GPI IgA, P?=?0.0793). Stroke risk could be better reclassified by aCL and a?2GPI, in association with both net reclassification improvement and integrated discrimination improvement statistics (P?
CONCLUSION:
aCL and a?2GPI are associated with ischaemic stroke and have added value for stroke risk prediction.
© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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OUTCOMES OF LOCAL AND REGIONAL ANESTHESIA FOR SUPERFICIALIZATION OF BRACHIOBASILIC ARTERIOVENOUS FISTULAS.
Ann Vasc Surg2019 Nov;():. doi: S0890-5096(19)30968-9.
Marsh Cléa, Holloway Janell, Sareh Sohail, Kansal Nikhil, Bowens Nina, Moazzez Ashkan, Tokhner Vadim, de Virgilio Christian, Archie Mark,
Abstract
BACKGROUND:
Superficialization, the second stage of a two-stage brachio-basilic arteriovenous fistula (BB-AVF), can be performed under local (LA), regional (RA), or general anesthesia (GA). Given the numerous comorbidities in patients with end-stage renal disease (ESRD), our preference is to use RA or LA when feasible. Our goal was to review the success rate of RA and LA, need for conversion to GA, and cardiac morbidity and mortality for BB-AVF superficialization.
METHODS:
We performed a retrospective cohort analysis of patients who underwent BB-AVF creation with second-stage superficialization over a four-year period. The primary outcome measures included need for conversion to GA, myocardial infarction (MI), and 30-day mortality. A secondary outcome was total operative time (time from pre-operative briefing to the time the patient left the operating room). We analyzed the data using Fisher Exact test for categorical data, and non-parametric analysis for continuous data.
RESULTS:
There were 42 patients who underwent BB-AVF superficialization. The median age was 56 years, with a mean body mass index of 29. Most patients were male (55%), and predominantly Hispanic/Latino (60%). RA was utilized in 35 patients (83%), LA in 5 (12%,) and GA in 2 (5%). The conversion rate from RA to GA was 0%, and was 20% (n=1) from LA to GA. There were no postoperative MI or deaths. There was no significant difference in total operative time (219.6 minutes for RA, 234.5 minutes for LA, and 278 minutes for GA, (p= 0.37)).
CONCLUSION:
Local and/or regional anesthesia can be successfully used in the majority of patients undergoing BB-AVF superficialization. LA and RA are associated with negligible cardiac morbidity and mortality. Conversion from RA to GA is rare. Use of RA does not result in a longer total operative time.
Copyright © 2019. Published by Elsevier Inc.
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The Progress and Significance of QRS Duration by Electrocardiography in Hypoplastic Left Heart Syndrome.
Pediatr Cardiol2019 Nov;():. doi: 10.1007/s00246-019-02237-6.
Karikari Yaa, Abdulkarim Mubeena, Li Yi, Loomba Rohit S, Zimmerman Frank, Husayni Tarek,
Abstract
Patients with hypoplastic left heart syndrome (HLHS) are now surviving through to Fontan palliation and beyond, however, with increased morbidity and mortality. Prolonged QRSd has become one of the predictors of morbidity and mortality in certain congenital heart diseases. There is limited data characterizing the QRSd in patients with HLHS. We aimed to describe the changes in QRSd at various times during the lifetime and to evaluate whether QRSd correlates with a higher risk of developing a composite endpoint of heart failure, heart transplant, or death. We conducted a retrospective chart review of patients with HLHS who survived Fontan palliation. QRSd was measured on ECGs at various stages pre- and postsurgical palliations and subsequently at 5 year intervals. Patients with a composite endpoint were compared to those without. A total of 89 patients were included in the final analysis. The QRSd increased significantly with time from 68.7?±?9.0 ms prior to Norwood to 91.0?±?14.0 ms immediately following Fontan and 104.7?±?13.6 ms 15 years after Fontan (p??120 ms was independently related to a greater frequency of composite endpoint and this was confirmed by a Kaplan-Meier analysis (p?=?0.011). This study unveils a novel relationship between QRSd of 120 ms or more with the composite endpoint. Despite the low sensitivity, this finding on a routine surveillance ECG could help identify HLHS Fontan patients at risk for heart failure, heart transplant, or death.
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A tangled tale of microRNA and cardiac fibrosis.
Clin Sci (Lond)2019 Nov;133(21):2217-2220. doi: 10.1042/CS20190866.
Chandy Mark,
Abstract
Cardiac fibrosis is important for wound healing, regeneration and producing the extracellular matrix (ECM) that provides the scaffold for cells. In pathological situations, fibroblasts are activated and remodel the ECM. In volume 133, issue 17 of Clinical Science, Yang et al. discovered that the miR-214-3p/NLRC5 axis is important for fibroblast-to-myofibroblast transition (FMT) and ECM remodelling in a pressure overload model of fibrosis [Clin. Sci. (2019) 133(17), 1845-1856]. This discovery helps to explain the complicated regulation of cardiac fibrosis. It also underscores the need for more investigation into the mechanisms of cardiac fibrosis to develop better diagnostic modalities and therapeutic options in heart failure.
© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
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Occurence of First and Recurrent Major Adverse Cardiovascular Events With Liraglutide Treatment Among Patients With Type 2 Diabetes and High Risk of Cardiovascular Events: A Post Hoc Analysis of a Randomized Clinical Trial.
JAMA Cardiol2019 Nov;():. doi: 10.1001/jamacardio.2019.3080.
Verma Subodh, Bain Stephen C, Buse John B, Idorn Thomas, Rasmussen Søren, Ørsted David D, Nauck Michael A,
Abstract
Importance:
After the occurrence of nonfatal cardiovascular events, recurrent events are highly likely. Most cardiovascular outcomes trials analyze first events only; extending analyses to first and recurrent (total) events can provide clinically meaningful information.
Objective:
To investigate whether liraglutide is associated with reduced first and recurrent total major adverse cardiovascular events (MACE) compared with placebo among patients with type 2 diabetes and high risk of cardiovascular events.
Design, Setting, and Participants:
This post hoc analysis of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) randomized, double-blind, clinical trial included data from patients with type 2 diabetes who had established or were at high risk for cardiovascular disease at 410 sites in 32 countries from August 2010, to December 2015. Data analysis was performed from August 15, 2016, to July 5, 2019.
Interventions:
Patients were randomized 1:1 to receive liraglutide (up to 1.8 mg per day) or placebo, both with standard care, for 3.5 to 5.0 years.
Main Outcomes and Measures:
Assessed outcomes were MACE (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke), expanded MACE (primary MACE plus coronary revascularization and hospitalization for heart failure or unstable angina pectoris), and the individual end points.
Results:
The 9340 LEADER trial participants (6003 [64.3%] male; mean [SD] age, 64.3 [7.2] years) experienced 1605 total MACE (1302 first and 303 recurrent events; median follow-up, 3.8 years [range, 0-5.2 years]). Patients who experienced any MACE were older (1 MACE: mean [SD] age, 65.6 [8.0] years; >1 MACE: 65.7 [7.9] years) and had diabetes for longer duration (1 MACE: mean [SD] duration, 13.4 [8.3] years; >1 MACE: 14.4 [8.7] years) compared with patients without MACE (mean [SD] age, 64.1 [7.1] years; mean [SD] duration, 12.7 [7.9] years). Fewer first and recurrent MACE occurred in the liraglutide group (n = 4668; 608 first and 127 recurrent events) than in the placebo group (n = 4672; 694 first and 176 recurrent events). Liraglutide was associated with a 15.7% relative risk reduction in total MACE (hazard ratio [HR], 0.84; 95% CI, 0.76-0.93) and a 13.4% reduction in total expanded MACE (HR, 0.87; 95% CI, 0.81-0.93) compared with placebo. For most individual cardiovascular end points, liraglutide was associated with lower risk vs placebo.
Conclusions and Relevance:
These results suggest that liraglutide treatment is associated with reduced total MACE compared with placebo among patients with type 2 diabetes and high risk of cardiovascular events. This analysis supports the findings of an absolute benefit of liraglutide treatment with respect to the overall burden of cardiovascular events in this high-risk patient population.
Trial Registration:
ClinicalTrials.gov identifier: NCT01179048.
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Cardioprotection conferred by SGLT2 inhibitors: a renal proximal tubule perspective.
Am J Physiol Cell Physiol2019 Nov;():. doi: 10.1152/ajpcell.00275.2019.
Silva Dos Santos Danúbia, Polidoro Juliano Z, Borges Junior Flávio A, Girardi Adriana C C,
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors, also known as gliflozins, improve glycemia by suppressing glucose reuptake in the renal proximal tubule. Currently, SGLT2 inhibitors are primarily indicated as antidiabetic agents; however, their benefits extend far beyond glucose control. Cardiovascular outcome trials indicated that all studied SGLT2 inhibitors remarkably and consistently reduce cardiovascular mortality and hospitalization for heart failure (HF) in type 2 diabetes (T2D) patients. Nevertheless, the mechanisms underlying the unprecedented cardiovascular benefits of gliflozins remain elusive. Multiple processes that directly or indirectly improve myocardial performance may be involved, including the amelioration of proximal tubular dysfunction. Therefore, this paper provides a perspective on the potential cellular and molecular mechanisms of the proximal tubule that may, at least in part, mediate the cardioprotection conferred by SGLT2 inhibitors. Specifically, we focus on the effects of SGLT2 on extracellular volume homeostasis, including its plausible functional and physical association with the apical Na/H exchanger isoform 3 (NHE3) as well its complex and its possible bidirectional interactions with the intrarenal angiotensin system and renal sympathetic nervous system. We also discuss evidence supporting a potential benefit of gliflozins in reducing cardiovascular risk, attributable to their effect on proximal tubule handling of uric acid and albumin as well as in erythropoietin production. Unraveling the mechanisms behind the beneficial actions of SGLT2 inhibitors may not only contribute to a better understanding of the pathophysiology of cardiovascular diseases but also enable repurposing of gliflozins to improve the routine management of HF patients with or without T2D.
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[PREECLAMPSIA: PATHOGENESIS AND MECHANISMS BASED THERAPEUTIC APPROACHES].
Harefuah2019 Nov;158(11):742-747.
Armaly Zaher, Zaher Maha, Knaneh Safa, Abassi Zaid,
Abstract
INTRODUCTION:
Preeclampsia is a serious complication of pregnancy affecting 3-8% of all pregnancies. It increases the morbidity and mortality of both the fetus and the pregnant woman, especially in developing countries. It deleteriously affects several vital organs, including the kidney, heart, liver, brain, and lung. Although, the pathogenesis of preeclampsia has not yet been fully understood, growing evidence suggests that aberrations in the angiogenic factors levels/activity and coagulopathy are responsible for the clinical manifestations of the disease. The common nominator of tissue damage of all these target organs is endothelial injury, which impedes their normal function. At the renal level, glomerular endothelial injury leads to the development of maternal hypertension and proteinuria. Similarly, this disease can cause hepatic and neurologic dysfunction due to vascular damage. The current review summarizes the recent development in the pathogenesis of this disease state with special focus on novel diagnostic biomarkers and their relevance to potential therapeutic options for preeclampsia. Specifically, we will highlight the renal manifestations of the diseases with emphasis on the involvement of angiogenic factors in vascular injury and how restoration of the angiogenic balance affects the renal and cardiovascular outcome of preeclamptic women.
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Impact of high on-treatment platelet reactivity on outcomes following PCI in patients on hemodialysis: An ADAPT-DES substudy.
Catheter Cardiovasc Interv2019 Nov;():. doi: 10.1002/ccd.28577.
Rubin Geoffrey A, Kirtane Ajay J, Chen Shmuel, Redfors Björn, Weisz Giora, Baber Usman, Zhang Yiran, Stuckey Thomas D, Witzenbichler Bernhard, Rinaldi Michael J, Neumann Franz-Josef, Metzger D Christopher, Henry Timothy D, Cox David A, Duffy Peter L, Brodie Bruce R, Mazzaferri Ernest L, Mehran Roxana, Ali Ziad A, Ben-Yehuda Ori, Stone Gregg W,
Abstract
OBJECTIVES:
We sought to compare clinical outcomes after percutaneous coronary intervention (PCI) in patients on versus not on hemodialysis (HD) and examine whether high on-treatment platelet reactivity (HPR) further impacts outcomes among patients on HD.
BACKGROUND:
Both chronic kidney disease (CKD) and HPR are predictors of major adverse cardiac events (MACE) after PCI.
METHODS:
Two-year outcomes of patients from the prospective, multicenter ADAPT-DES study (N = 8,582) were analyzed according to HD status at enrollment. All patients underwent platelet function testing with the VerifyNow assay; HPR on clopidogrel was defined as P2Y12 reaction units (PRU) >208.
RESULTS:
Compared with non-HD patients, patients on HD (n = 85) had significantly higher baseline PRU (median 254 vs. 188, p = .001) and more frequently had HPR (61.7% vs. 42.5%, p?
CONCLUSIONS:
Nearly two-thirds of patients on HD exhibited HPR on clopidogrel, and both HD and HPR were independently associated with 2-year adverse outcomes after DES implantation. However, the deleterious impact of HD on clinical outcomes was present in both patients with and without HPR.
© 2019 Wiley Periodicals, Inc.
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Troponins and brain natriuretic peptides for the prediction of cardiotoxicity in cancer patients: a meta-analysis.
Eur J Heart Fail2019 Nov;():. doi: 10.1002/ejhf.1631.
Michel Lars, Mincu Raluca I, Mahabadi Amir A, Settelmeier Stephan, Al-Rashid Fadi, Rassaf Tienush, Totzeck Matthias,
Abstract
AIMS:
Cardiac biomarkers are a mainstay in diagnosis of cardiovascular disease but their role in cardio-oncology has not yet been systematically evaluated. This meta-analysis aims to determine whether cardiac troponins and (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) predict cancer therapy-related left ventricular (LV) dysfunction.
METHODS AND RESULTS:
Scientific databases were searched for studies that assessed troponins or BNP/NT-proBNP in adult patients undergoing cancer therapy. Data from 61 trials with 5691 patients were included. Cancer therapy was associated with an increase in troponin levels [odds ratio (OR) 14.3, 95% confidence interval (CI) 6.0-34.1; n = 3049]. Patients with elevated troponins receiving chemotherapy or human epidermal growth factor receptor 2 inhibitor therapy were at higher risk for LV dysfunction (OR?11.9, 95% CI 4.4-32.1; n = 2163). Troponin had a negative predictive value of 93%. Mean BNP/NT-proBNP levels were increased in patients post-treatment (standardized mean difference 0.6, 95% CI 0.3-0.9; n = 912), but the available evidence did not consistently indicate prediction of LV dysfunction (OR 1.7, 95% CI 0.7-4.2; n = 197). ?-blocker and angiotensin-converting enzyme inhibitor therapy to mitigate cardiotoxicity during cancer therapy was associated with a decline in serum troponins (OR 4.1, 95% CI 1.7-9.8; n = 466).
CONCLUSION:
Elevated troponin levels predict LV dysfunction in patients receiving cancer therapy. Assessment of troponin levels may qualify as a screening test to identify patients who require referral to cardio-oncology units and benefit from preventive strategies. Further evidence is required for both biomarkers.
© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Expression profiling and bioinformatics analysis of circulating microRNAs in patients with acute myocardial infarction.
J Clin Lab Anal2019 Nov;():e23099. doi: 10.1002/jcla.23099.
Zhong Zhixiong, Wu Heming, Zhong Wei, Zhang Qifeng, Yu Zhikang,
Abstract
OBJECTIVE:
Acute Myocardial Infarction (AMI) is the most severe type of coronary atherosclerotic heart diseases. MiRNA is a class of endogenous noncoding small molecule RNA, which plays an important regulatory role in the development of some diseases.
METHODS:
We examined the miRNA expression profiles in 16 patients with AMI compared with 6 non-AMI controls using RNA sequencing.
RESULTS:
Compared with the miRNA expression profiles of non-AMI controls, a total of 181 differentially expressed miRNAs were discriminated in AMI patients, of which 96 upregulated miRNAs and 85 downregulated miRNAs. The top ten upregulated miRNAs were as follows: miR-449a-5p, miR-126-5p, miR-93-5p, miR-199a-3p, miR-4454, miR-6880-3p, miR-3135a, miR-548ad-5p, miR-4508, and miR-556-5p; while the top ten downregulated were as follows: miR-6805-5p, miR-1228-5p, miR-939-5p, miR-615-3p, miR-6780a-5p, miR-6857-3p, miR-5088-55p, miR-7155-3p, miR-184, and miR-4525. And the qRT-PCR results of differentially expressed miRNAs showed the same result as high-throughput sequencing data. For these 181 differentially expressed miRNAs, 19 841 target genes were predicted by GO analysis. The enrichment analysis revealed 2061 involved in biological processes, 353 in molecular function and 303 in cellular components. To identify biological pathways in AMI as compared to non-AMI, the target genes of differentially expressed miRNAs were mapped to the classical signal transduction pathway in KEGG, indicating that 214 classes were enriched. ROC analysis showed that the circulating miRNAs had the important value for AMI diagnosis and supported the previous conclusions that circulating miRNAs were effective to diagnose the AMI as a novel biomarker.
CONCLUSIONS:
Our findings require further research to confirm. It may provide a meaningful reference for the diagnosis and treatment of AMI.
© 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.
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Enhancing respiratory sinus arrhythmia increases cardiac output in rats with left ventricular dysfunction.
J Physiol2019 Nov;():. doi: 10.1113/JP277293.
O'Callaghan Erin L, Lataro Renata M, Roloff Eva L, Chauhan Ashok S, Salgado Helio C, Duncan Edward, Nogaret Alain, Paton Julian F R,
Abstract
KEY POINTS:
Respiratory sinus arrhythmia is physiological pacing of the heart that disappears in cardiovascular disease and is associated with poor cardiac prognosis In heart failure, cardiac pacing has little if any variation in rate at rest We proposed that reinstatement of respiratory sinus arrhythmia would improve cardiac function in rats with heart failure Heart failure rats were paced daily for 2 weeks with either respiratory sinus arrhythmia or paced monotonically at a matched heart rate; cardiac function was measured using non invasive echocardiography Cardiac output and stroke volume were increased in rats paced with respiratory sinus arrhythmia compared to monotonic-pacing, via improvement in systolic function that persisted beyond the pacing treatment period We propose that respiratory sinus arrhythmia pacing reverse-remodels the heart in heart failure and is worth considering as a new form of cardiac pacemaking.
ABSTRACT:
Natural pacing of the heart results in heart rate variability, an indicator of good health and cardiac function. A contributor to heart rate variability is respiratory sinus arrhythmia or RSA - an intrinsic respiratory modulated pacing of heart rate. The loss of RSA is associated with poor cardiac prognosis and sudden cardiac death. We tested if reinstatement of respiratory modulated heart rate (RMH) would improve cardiac performance in heart failure. Heart failure was induced in Wistar rats by ligation of the left anterior descending coronary artery. Rats were unpaced, monotonic paced and RMH paced; the latter had the same average heart rate as the monotonic paced animals. Cardiac function was assessed non-invasively using echocardiography before and after two weeks of daily pacing at a time when pacing was turned off. RMH increased cardiac output by 20 ± 8 % compared to monotonic pacing (-3 ± 5 %; P<0.05). This improvement in cardiac output was associated with an increase in stroke volume compared to monotonic pacing (P = 0.03) and improvement in circumferential strain (P = 0.02). Improvements in ejection fraction (P = 0.08) and surrogate measures of left ventricle compliance did not reach significance. Increases in contractility (P<0.05) and coronary blood flow (P<0.05) were seen in vitro during variable pacing to mimic RMH. Thus, in rats with left ventricular dysfunction, chronic RMH pacing improved cardiac function through improvements in systolic function. As these improvements were made with pacing switched off, we propose the novel idea that RMH pacing causes reverse-remodelling. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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Measuring cardiopulmonary complications of carfilzomib treatment and associated risk factors using the SEER-Medicare database.
Cancer2019 Nov;():. doi: 10.1002/cncr.32601.
Fakhri Bita, Fiala Mark A, Shah Nina, Vij Ravi, Wildes Tanya M,
Abstract
BACKGROUND:
Carfilzomib improves survival in patients with recurrent myeloma. Given the strict eligibility criteria in clinical trials, the actual frequency of cardiac adverse events (CAEs) and pulmonary adverse events (PAEs) and the risk factors associated with these AEs in the general population need to be established.
METHODS:
The authors extracted myeloma cases in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database from 2000 through 2013 and corresponding claims through 2014. They then identified patients who received carfilzomib during their disease course. Subsequently, the International Classification of Diseases, Ninth Revision (ICD-9) was used to identify all the codes for CAEs, PAEs, and respiratory infections associated with carfilzomib use. Preexisting diagnoses corresponding to the CAEs and PAEs of interest were excluded to distinguish toxicity from comorbidity. Multivariate Cox regression was performed to determine those variables independently associated with the development of CAEs and PAEs.
RESULTS:
Of the 635 patients analyzed, the median age was 72 years (range, 36-94 years); 55% of the patients were male and 79% were white. The median duration of carfilzomib treatment was 58 days (range, 1-716 days). Overall, approximately 66% of the patients had codes for either CAEs or PAEs. In terms of CAEs, approximately 22% of patients developed hypertension, 15% developed peripheral edema, and 14% experienced heart failure. With regard to PAEs, approximately 28% of patients developed dyspnea, 15% developed cough, and 15% developed pneumonia. Only chronic obstructive pulmonary disease (COPD) was found to be independently associated with the development of CAEs. Patients with preexisting COPD were found to have a 40% increase in their hazard of developing CAEs (adjusted hazard ratio, 1.40; 95% CI, 1.03-1.90).
CONCLUSIONS:
In older adults with myeloma who are undergoing treatment with carfilzomib, new cardiac and pulmonary diagnoses were common. Patients with preexisting COPD were found to be at an increased risk of developing CAEs.
© 2019 American Cancer Society.
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Serum Exosome MicroRNAs Predict Multiple Sclerosis Disease Activity after Fingolimod Treatment.
Mol Neurobiol2019 Nov;():. doi: 10.1007/s12035-019-01792-6.
Ebrahimkhani Saeideh, Beadnall Heidi N, Wang Chenyu, Suter Catherine M, Barnett Michael H, Buckland Michael E, Vafaee Fatemeh,
Abstract
We and others have previously demonstrated the potential for circulating exosome microRNAs to aid in disease diagnosis. In this study, we sought the possible utility of serum exosome microRNAs as biomarkers for disease activity in multiple sclerosis patients in response to fingolimod therapy. We studied patients with relapsing-remitting multiple sclerosis prior to and 6 months after treatment with fingolimod. Disease activity was determined using gadolinium-enhanced magnetic resonance imaging. Serum exosome microRNAs were profiled using next-generation sequencing. Data were analysed using univariate/multivariate modelling and machine learning to determine microRNA signatures with predictive utility. Accordingly, we identified 15 individual miRNAs that were differentially expressed in serum exosomes from post-treatment patients with active versus quiescent disease. The targets of these microRNAs clustered in ontologies related to the immune and nervous systems and signal transduction. While the power of individual microRNAs to predict disease status post-fingolimod was modest (average 77%, range 65 to 91%), several combinations of 2 or 3 miRNAs were able to distinguish active from quiescent disease with greater than 90% accuracy. Further stratification of patients identified additional microRNAs associated with stable remission, and a positive response to fingolimod in patients with active disease prior to treatment. Overall, these data underscore the value of serum exosome microRNA signatures as non-invasive biomarkers of disease in multiple sclerosis and suggest they may be used to predict response to fingolimod in future clinical practice. Additionally, these data suggest that fingolimod may have mechanisms of action beyond its known functions.
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Benefits, risks and impacts on quality of life of medications used in multimorbid older adults: a Delphi study.
Int J Clin Pharm2019 Nov;():. doi: 10.1007/s11096-019-00935-y.
Sirois Caroline, Lunghi Carlotta, Berthelot William, Laroche Marie-Laure, Frini Anissa,
Abstract
Background Multimorbidity and polypharmacy are common in older people. Despite the existence of quality criteria for medication use among this population, there is little guidance for managing the complex pharmacological arsenal in a multimorbidity context. Objective To establish consensus on benefits, risks and impacts on quality of life of medications used in an older adult with three chronic diseases that require complex pharmacotherapy. Setting International experts in pharmacology. Method A panel of experts responded to three rounds of a Delphi survey. They assessed the benefits, risks and positive impacts on quality of life of 50 different medications or medication classes that could be used by a hypothetical multimorbid older patient aged 65-75 years, with type 2 diabetes, heart failure and chronic obstructive pulmonary disease. Each aspect was evaluated on a 5-level Likert scale. Main outcome measure Percentage of agreement on each of the three aspects for all medication. Results Consensus was reached on 95% of items (166/174). Only two medication classes were associated with both the highest category of benefits and positive impacts on quality of life, and the lowest risk category: long-acting anticholinergics and long-acting beta-2-agonists. Nine other medications/classes of medications were categorized within the highest benefits level (metformin, DPP-4-inhibitors, short-acting beta-2-agonists, ACE inhibitors, beta-blockers, warfarin, non-vitamin K oral anticoagulants, nitrates and acetaminophen). Fifteen medications were included in the highest level of risks, among which warfarin and Non-vitamin K oral anticoagulants. Conclusions Medications recommended in clinical guidelines for individual diseases are generally considered positive for multimorbid older patients. Nevertheless, a non-negligible number of medications was deemed negative or very negative by our panelists. For multimorbid patients, individualizing treatment according to their preferences seems of utmost importance.
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[Atrial fibrillation : Recent studies and new treatment options].
Herzschrittmacherther Elektrophysiol2019 Nov;():. doi: 10.1007/s00399-019-00657-8.
Bergau Leonard, Sohns Christian, Sommer Philipp,
Abstract
Catheter ablation by pulmonary vein isolation (PVI) is established in patients suffering from drug-refractory symptomatic atrial fibrillation (AF). According to recent guidelines, it can also be offered to AF patients as a first-line treatment. The CASTLE-AF study randomized AF patients with severely impaired left ventricular (LV) function to catheter ablation or drug therapy. The patients in the ablation group experienced a significantly lower all-cause mortality and hospitalization rate compared to the conservatively managed group. This result is supported by the CAMERA-MRI trial. The benefit of AF ablation in heart failure was not reproducible in the large randomized CABANA trial. Due to a high cross-over rate, the results are vigorously being discussed and the consequences for clinical practice remain unclear. The DECAAF study described a positive correlation with left atrial fibrosis and the risk for recurrence following PVI. Whether those fibrotic areas should be targeted during the first ablation attempt is now part of the ongoing DECAAF-II trial. Its results might affect the preprocedural planning phase and future ablation strategies. Finally, new ablation techniques are being investigated. In this context, high-power short-duration ablation (HPSD) is of growing interest. In the QDOT-FAST trial, the procedure and fluoroscopy times could be significantly reduce using HPSD catheter technology. However, future studies are still required to evaluate the long-term performance of this novel ablation approach.
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Left Superior Vena Cava in the Fetus: A Rarely Isolated Anomaly.
Pediatr Cardiol2019 Nov;():. doi: 10.1007/s00246-019-02246-5.
Minsart Anne-Frédérique, Boucoiran Isabelle, Delrue Marie-Ange, Audibert François, Abadir Sylvia, Lapierre Chantale, Lemyre Emmanuelle, Raboisson Marie-Josée,
Abstract
The frequency of chromosomal anomalies among fetuses with isolated persistent left superior vena cava (PLSVC) is still debated. The objective of the present study was to assess the prevalence of genetic and morphological anomalies identified in fetuses with PLSVC. We conducted a single-center retrospective study including all fetuses diagnosed with a PLSVC between 2010 and 2017. PLSVC was categorized as isolated or associated according to antenatal diagnosis of associated congenital heart defects, hypoplastic aortic isthmus, abnormal venous/arterial connections, and extracardiac anomalies. Among 229 fetuses diagnosed with PLSVC, 39 cases (17%) were strictly isolated and no syndromic/genetic anomaly or aortic coarctation was diagnosed. Seventy-two fetuses had a cardiovascular defect with a rate of genetic anomalies of 22%, 29 had an extracardiac malformation, and 89 had both an extracardiac and a cardiovascular defect. Among fetuses with abnormal development of the arterial/venous system as the only associated anomaly such as aberrant right subclavian artery or absent ductus venosus, 22% had a genetic anomaly. Overall, sixty-five fetuses or infants had a genetic concern, including 23 aneuploidies, 15 pathogenic micro-deletions/duplications, and 5 variants of unknown significance; 12 patients had VACTERL association, and 12 heterotaxy syndrome. Seven infants had an aortic coarctation diagnosed at birth.In conclusion, a thorough prenatal ultrasound examination is paramount, and the identification of variants of the venous/arterial system in addition to PLSVC should raise suspicion for genetic or morphologic abnormalities. Invasive prenatal diagnosis with array-CGH should be offered when PLSVC is non-isolated, after a detailed ultrasound evaluation in a tertiary center.
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[Noninformative coding of causes of death in cardiovascular deaths: effects on the mortality rate for ischemic heart disease].
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz2019 Nov;():. doi: 10.1007/s00103-019-03050-5.
Stolpe Susanne, Stang Andreas,
Abstract
BACKGROUND:
The validity of mortality statistics is specific to causes of death and depends on the quality of death certificates. The proportion of noninformative underlying causes of death in all deaths is an indicator for the validity of a mortality statistic. The most frequent noninformative cause of death involves cardiovascular diseases (ICD-10: I00-I99).
OBJECTIVES:
Regional differences in the frequency and type of use of noninformative cardiovascular causes of death are investigated and their effect on the mortality rate of ischemic heart disease is presented.
MATERIALS AND METHODS:
Mortality rates for cardiovascular causes of death by gender, age group, and federal state were extracted from the Information System of the Federal Health Monitoring (GBE) for 2000, 2010, 2015, and 2016. The proportion of noninformative causes of death in all cardiovascular deaths, as well as the mortality rate for ischemic heart disease after recoding noninformative causes of death, were calculated.
RESULTS:
The proportion of noninformative causes of death in all cardiovascular deaths is high and depends on age, sex, federal state, and year of death. Regional differences in frequency and type of use were found. After recoding selected noninformative causes of death, the mean increase in the mortality rate for ischemic heart disease in all federal states was 33%.
DISCUSSION:
A comparison of cause-specific mortality rates between regions, sexes, and over time is affected by differences in the use of noninformative causes of death. Improving the quality of death certificates is a prerequisite for valid mortality statistics.
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Association of Migraine and Ischemic Heart Disease: A Review.
Cureus2019 Sep;11(9):e5719. doi: 10.7759/cureus.5719.
Saeed Aisha, Rana Kiran F, Warriach Zain I, Tariq Muhammad Ali, Malik Bilal Haider,
Abstract
Many new studies have shown an association between migraine and ischemic heart disease, and the association seems to be multi-factorial. This article reviews what is already known about this linkage and further investigates if migraine is a risk factor for cardiovascular disease. The literature search for this article was performed primarily using PubMed as the search engine. Only those articles that assessed migraine as exposure and cardiovascular events as outcomes were included. Also, articles only from the last five years with full-text and human studies were reviewed. Based on our investigation and as indicated by previous studies, migraine headache is associated with different kinds of cardiovascular events. Healthcare providers need to be aware of this association so that they can assess and manage their migraine patients better.
Copyright © 2019, Saeed et al.
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Initial Experience of Minimally Invasive Concomitant Aortic and Mitral Valve Replacement/Repair at a Tertiary Care Cardiac Centre of a Developing Country.
Cureus2019 Sep;11(9):e5707. doi: 10.7759/cureus.5707.
Zia Kashif, Mangi Ali R, Bughio Hafeezullah, Tariq Khuzaima, Chaudry Pervaiz A, Karim Musa,
Abstract
Introduction Minimally invasive double valve replacement (DVR) surgery through a small transverse anterior thoracotomy is an alternate technique to sternotomy for concomitant aortic and mitral valve (AVR, MVR) surgery. The aim of this study was to evaluate the in-hospital and early outcomes of direct vision minimal invasive double valve surgery (DVMI-DVR) at a tertiary care cardiac center of a developing country. Methods This study was conducted at the National Institute of Cardiovascular Diseases Karachi, Pakistan from January 2018 to September 2018. Nineteen consecutive patients undergoing DVMI-DVR for aortic and mitral disease without any prior cardiac surgery were included in this study. For all procedures, access was obtained through small transverse anterior thoracotomy incision with wedge resection (Chaudhry's Wedge) of sternum opposite to the third and fourth costosternal joints. Patients were observed during their hospital stay and the following variables were observed the length of hospital stay (LOHS), ventilator support, intensive care unit (ICU) stay, pain score, and mortality. The pain score was assessed using the visual analog scale (VAS). Results The male/female ratio was 11:8 with a mean age of 35 ± 12 years with mean EuroSCORE of 6.6 ± 3.5%. The mean total bypass time was 129.8 ± 23.83 min (range: 98-181 minutes). The mean mechanical ventilation time was 3.16 ± 1.12 hours (range: 2-6 hours). The mean intensive care unit (ICU) stay was 41.84 ± 8.36 hours. The mean post-operative LOHS was 5.63 ± 1.12 days (range: 4-8 days). We had zero frequency of wound infection and surgical mortality. The mean pain score was 4.32 (on a predefined pain scale of one to nine with a high value indicating severe pain). Conclusion Minimally invasive DVR surgery is a safe and reproducible technique with comparable outcomes such as postoperative pain score (4.32 ± 2.05), ventilation time (3.16 ± 1.12 hours), ICU stay (41.84 ± 8.36 hours), and hospital stay (5.63 ± 1.12 days). In terms of mortality, operative times, ICU stay, and hospital stay, the minimally invasive DVR is at least comparable to those achieved with median sternotomy. Further prospective randomized studies are needed to validate our findings.
Copyright © 2019, Zia et al.
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