Abstract Microbes play an important role in human health and disease. In the setting of heart failure (HF), substantial hemodynamic changes, such as hypoperfusion and congestion in the intestines, ...can alter gut morphology, permeability, function, and possibly the growth and composition of gut microbiota. These changes can disrupt the barrier function of the intestines and exacerbate systemic inflammation via microbial or endotoxin translocation into systemic circulation. Furthermore, cardiorenal alterations via metabolites derived from gut microbiota can potentially mediate or modulate HF pathophysiology. Recently, trimethylamine N -oxide (TMAO) has emerged as a key mediator that provides a mechanistic link between gut microbiota and multiple cardiovascular diseases, including HF. Potential intervention strategies which may target this microbiota-driven pathology include dietary modification, prebiotics/probiotics, and selective binders of microbial enzymes or molecules, but further investigations into their safety and efficacy are warranted.
Advances in our understanding of how the gut microbiota contributes to human health and diseases have expanded our insight into how microbial composition and function affect the human host. Heart ...failure is associated with splanchnic circulation congestion, leading to bowel wall oedema and impaired intestinal barrier function. This situation is thought to heighten the overall inflammatory state via increased bacterial translocation and the presence of bacterial products in the systemic blood circulation. Several metabolites produced by gut microorganisms from dietary metabolism have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. These findings suggest that the gut microbiome functions like an endocrine organ by generating bioactive metabolites that can directly or indirectly affect host physiology. In this Review, we discuss several newly discovered gut microbial metabolic pathways, including the production of trimethylamine and trimethylamine N-oxide, short-chain fatty acids, and secondary bile acids, that seem to participate in the development and progression of cardiovascular diseases, including heart failure. We also discuss the gut microbiome as a novel therapeutic target for the treatment of cardiovascular disease, and potential strategies for targeting intestinal microbial processes.
The endothelium can evoke relaxations of the underlying vascular smooth muscle, by releasing vasodilator substances. The best‐characterized endothelium‐derived relaxing factor (EDRF) is nitric oxide ...(NO) which activates soluble guanylyl cyclase in the vascular smooth muscle cells, with the production of cyclic guanosine monophosphate (cGMP) initiating relaxation. The endothelial cells also evoke hyperpolarization of the cell membrane of vascular smooth muscle (endothelium‐dependent hyperpolarizations, EDH‐mediated responses). As regards the latter, hydrogen peroxide (H2O2) now appears to play a dominant role. Endothelium‐dependent relaxations involve both pertussis toxin‐sensitive Gi (e.g. responses to α2‐adrenergic agonists, serotonin, and thrombin) and pertussis toxin‐insensitive Gq (e.g. adenosine diphosphate and bradykinin) coupling proteins. New stimulators (e.g. insulin, adiponectin) of the release of EDRFs have emerged. In recent years, evidence has also accumulated, confirming that the release of NO by the endothelial cell can chronically be upregulated (e.g. by oestrogens, exercise and dietary factors) and downregulated (e.g. oxidative stress, smoking, pollution and oxidized low‐density lipoproteins) and that it is reduced with ageing and in the course of vascular disease (e.g. diabetes and hypertension). Arteries covered with regenerated endothelium (e.g. following angioplasty) selectively lose the pertussis toxin‐sensitive pathway for NO release which favours vasospasm, thrombosis, penetration of macrophages, cellular growth and the inflammatory reaction leading to atherosclerosis. In addition to the release of NO (and EDH, in particular those due to H2O2), endothelial cells also can evoke contraction of the underlying vascular smooth muscle cells by releasing endothelium‐derived contracting factors. Recent evidence confirms that most endothelium‐dependent acute increases in contractile force are due to the formation of vasoconstrictor prostanoids (endoperoxides and prostacyclin) which activate TP receptors of the vascular smooth muscle cells and that prostacyclin plays a key role in such responses. Endothelium‐dependent contractions are exacerbated when the production of nitric oxide is impaired (e.g. by oxidative stress, ageing, spontaneous hypertension and diabetes). They contribute to the blunting of endothelium‐dependent vasodilatations in aged subjects and essential hypertensive and diabetic patients. In addition, recent data confirm that the release of endothelin‐1 can contribute to endothelial dysfunction and that the peptide appears to be an important contributor to vascular dysfunction. Finally, it has become clear that nitric oxide itself, under certain conditions (e.g. hypoxia), can cause biased activation of soluble guanylyl cyclase leading to the production of cyclic inosine monophosphate (cIMP) rather than cGMP and hence causes contraction rather than relaxation of the underlying vascular smooth muscle.
Despite major strides in reducing cardiovascular disease (CVD) burden with modification of classic CVD risk factors, significant residual risks remain. Recent discoveries that linked intestinal ...microbiota and CVD have broadened our understanding of how dietary nutrients may affect cardiovascular health and disease. Although next-generation sequencing techniques can identify gut microbial community participants and provide insights into microbial composition shifts in response to physiological responses and dietary exposures, provisions of prebiotics or probiotics have yet to show therapeutic benefit for CVD. Our evolving understanding of intestinal microbiota-derived physiological modulators (e.g., short-chain fatty acids) and pathogenic mediators (e.g., trimethylamine N-oxide) of host disease susceptibility have created novel potential therapeutic opportunities for improved cardiovascular health. This review discusses the roles of human intestinal microbiota in normal physiology, their associations with CVD susceptibilities, and the potential of modulating intestinal microbiota composition and metabolism as a novel therapeutic target for CVD.
In recent years, rapid changes and improvements have been witnessed in the field of transformer condition monitoring and assessment, especially with the advances in computational intelligence ...techniques. Condition Monitoring and Assessment of Power Transformers Using Computational Intelligence applies a broad range of computational intelligence techniques to deal with practical transformer operation problems. The approaches introduced are presented in a concise and flowing manner, tackling complex transformer modelling problems and uncertainties occurring in transformer fault diagnosis. Condition Monitoring and Assessment of Power Transformers Using Computational Intelligence covers both the fundamental theories and the most up-to-date research in this rapidly changing field. Many examples have been included that use real-world measurements and realistic operating scenarios of power transformers to fully illustrate the use of computational intelligence techniques for a variety of transformer modelling and fault diagnosis problems. Condition Monitoring and Assessment of Power Transformers Using Computational Intelligence is a useful book for professional engineers and postgraduate students. It also provides a firm foundation for advanced undergraduate students in power engineering.
IMPORTANCE: Transcatheter aortic valve replacement (TAVR) indications are expanding, leading to an increasing number of patients with bicuspid aortic stenosis undergoing TAVR. Pivotal randomized ...trials conducted to obtain US Food and Drug Administration approval excluded bicuspid anatomy. OBJECTIVE: To compare the outcomes of TAVR with a balloon-expandable valve for bicuspid vs tricuspid aortic stenosis. DESIGN, SETTING, AND PARTICIPANTS: Registry-based prospective cohort study of patients undergoing TAVR at 552 US centers. Participants were enrolled in the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapies Registry from June 2015 to November 2018. EXPOSURES: TAVR for bicuspid vs tricuspid aortic stenosis. MAIN OUTCOMES AND MEASURES: Primary outcomes were 30-day and 1-year mortality and stroke. Secondary outcomes included procedural complications, valve hemodynamics, and quality of life assessment. RESULTS: Of 81 822 consecutive patients with aortic stenosis (2726 bicuspid; 79 096 tricuspid), 2691 propensity-score matched pairs of bicuspid and tricuspid aortic stenosis were analyzed (median age, 74 years interquartile range {IQR}, 66-81 years; 39.1%, women; mean SD STS-predicted risk of mortality, 4.9% 4.0% and 5.1% 4.2%, respectively). All-cause mortality was not significantly different between patients with bicuspid and tricuspid aortic stenosis at 30 days (2.6% vs 2.5%; hazard ratio HR, 1.04, 95% CI, 0.74-1.47) and 1 year (10.5% vs 12.0%; HR, 0.90 95% CI, 0.73-1.10). The 30-day stroke rate was significantly higher for bicuspid vs tricuspid aortic stenosis (2.5% vs 1.6%; HR, 1.57 95% CI, 1.06-2.33). The risk of procedural complications requiring open heart surgery was significantly higher in the bicuspid vs tricuspid cohort (0.9% vs 0.4%, respectively; absolute risk difference RD, 0.5% 95% CI, 0%-0.9%). There were no significant differences in valve hemodynamics. There were no significant differences in moderate or severe paravalvular leak at 30 days (2.0% vs 2.4%; absolute RD, 0.3% 95% CI, −1.3% to 0.7%) and 1 year (3.2% vs 2.5%; absolute RD, 0.7% 95% CI, −1.3% to 2.7%). At 1 year there was no significant difference in improvement in quality of life between the groups (difference in improvement in the Kansas City Cardiomyopathy Questionnaire overall summary score, −2.4 95% CI, −5.1 to 0.3; P = .08). CONCLUSIONS AND RELEVANCE: In this preliminary, registry-based study of propensity-matched patients who had undergone transcatheter aortic valve replacement for aortic stenosis, patients with bicuspid vs tricuspid aortic stenosis had no significant difference in 30-day or 1-year mortality but had increased 30-day risk for stroke. Because of the potential for selection bias and the absence of a control group treated surgically for bicuspid stenosis, randomized trials are needed to adequately assess the efficacy and safety of transcatheter aortic valve replacement for bicuspid aortic stenosis.
Gut Microbiota in Cardiovascular Health and Disease Tang, W.H Wilson; Kitai, Takeshi; Hazen, Stanley L
Circulation research,
2017-March-31, 2017-Mar-31, 2017-03-31, 20170331, Volume:
120, Issue:
7
Journal Article
Peer reviewed
Open access
Significant interest in recent years has focused on gut microbiota–host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and ...disease, including cardiovascular diseases. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. In addition to alterations in gut microbiota composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent studies revealed that gut microbiota can elicit a variety of effects on the host. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites, that can impact host physiology. Microbiota interact with the host through many pathways, including the trimethylamine/trimethylamine N-oxide pathway, short-chain fatty acids pathway, and primary and secondary bile acids pathways. In addition to these metabolism-dependent pathways, metabolism-independent processes are suggested to also potentially contribute to cardiovascular disease pathogenesis. For example, heart failure–associated splanchnic circulation congestion, bowel wall edema, and impaired intestinal barrier function are thought to result in bacterial translocation, the presence of bacterial products in the systemic circulation and heightened inflammatory state. These are thought to also contribute to further progression of heart failure and atherosclerosis. The purpose of the current review is to highlight the complex interplay between microbiota, their metabolites, and the development and progression of cardiovascular diseases. We will also discuss the roles of gut microbiota in normal physiology and the potential of modulating intestinal microbial inhabitants as novel therapeutic targets.
Purpose
Coronavirus disease (COVID-19) has rapidly emerged as a global health threat. The purpose of this article is to share our local experience of stepping up infection control measures in ...ophthalmology to minimise COVID-19 infection of both healthcare workers and patients.
Methods
Infection control measures implemented in our ophthalmology clinic are discussed. The measures are based on detailed risk assessment by both local ophthalmologists and infection control experts.
Results
A three-level hierarchy of control measures was adopted. First, for administrative control, in order to lower patient attendance, text messages with an enquiry phone number were sent to patients to reschedule appointments or arrange drug refill. In order to minimise cross-infection of COVID-19, a triage system was set up to identify patients with fever, respiratory symptoms, acute conjunctivitis or recent travel to outbreak areas and to encourage these individuals to postpone their appointments for at least 14 days. Micro-aerosol generating procedures, such as non-contact tonometry and operations under general anaesthesia were avoided. Nasal endoscopy was avoided as it may provoke sneezing and cause generation of droplets. All elective clinical services were suspended. Infection control training was provided to all clinical staff. Second, for environmental control, to reduce droplet transmission of COVID-19, installation of protective shields on slit lamps, frequent disinfection of equipment, and provision of eye protection to staff were implemented. All staff were advised to measure their own body temperatures before work and promptly report any symptoms of upper respiratory tract infection, vomiting or diarrhoea. Third, universal masking, hand hygiene, and appropriate use of personal protective equipment (PPE) were promoted.
Conclusion
We hope our initial experience in stepping up infection control measures for COVID-19 infection in ophthalmology can help ophthalmologists globally to prepare for the potential community outbreak or pandemic. In order to minimise transmission of COVID-19, ophthalmologists should work closely with local infection control teams to implement infection control measures that are appropriate for their own clinical settings.
PDF
