MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Zhoršení a rizikové faktory fibrilací

Deficit vitamínu B1



B3 vit. deficit



Biliary acids

  • Cholic acid and chenodeoxycholic acid
    • Subsequently conjugated in the liver with the amino acids taurine or glycine
  • Following secretion into the gut during food digestion
    • Intestinal microbiota causes their deconjugation and dihydroxylation
      • Via 7-alpha dehydroxylase
  • Form the secondary bile acids deoxycholic acid and lithocholic acid
    • Reabsorbed back into the liver via the portal veins
  • Enterohepatic circulation is disrupted during liver disease
    • Spillage of these metabolites into the systemic circulation
      • To end organ dysfunction
  • Wang et al. demonstrated that serum concentration of chenodeoxycholic acid
    • Was significantly higher in AF than in control patients
    • Positive association with left atrial size and low-voltage areas on electroanatomic mapping
  • The secondary bile acids glycolithocholate sulfate and glycocholenate sulfate
    • Significant association with the risk of AF in an African-American patient cohort
  • Impact of bile acids on the structure of the cardiomyocyte cell membrane
    • By causing direct damage to cardiac ion channels
    • Affecting Ca2+ signalling
    • Intracellular effect of bile acids on pathways that regulate Ca2+ homeostasis
      • Via muscarinic receptors or the bile acid receptor TGR5 (G-protein coupled bile acid receptor 1)
  • www.aerjournal.com/articles/gut-microbiota-and-atrial-fibrillation-pathogenesis-mechanisms-and-therapies

Glukoza

  • Healthy adult hearts
    • Use fatty acids and carbohydrates as their predominant fuel
  • Cardiac disease such as hypertrophy and heart failure
    • Often lead to a more prominent use of glycolytic energy production
  • Presence of diabetes
    • Myocardium relies more on the metabolism of fatty acids
    • Not as efficient as a mixed metabolism consistent with the utilization of both fatty acids and glucose
    • increased consumption of fatty acids
      • Metabolites such as diacylglycerol tend to accumulate in the myocardium
      • leads to increased interstitial and perivascular fibrosis
        • “diabetic cardiomyopathy” in the early 1970s
  • Heart failure are about twice as high in patients with than without diabetes
  • Diabetes is high in heart failure as well
  • Both diseases are risk factors for arrhythmias on the ventricular and on the atrial level
  • Disturbed metabolic pattern alone is discussed to promote arrhythmias and SCD
    • May be a point of action for SGLT2 inhibitors
      • Demonstrated to stabilize an impaired state of energy consumption of the heart
  • High glucose treatment induces
    • A cellular hypertrophy,
    • Reduced contractility,
    • Changes of the expression levels of the ryanodine receptor and the sodium-calcium exchanger (NCX)
  • Empagliflozin ameliorates high glucose-induced cardiac dysfunction on all mentioned levels
    • Must be interpreted with caution
    • Robust expression of SGLT2 in their cells which is markedly upregulated in their disease model
    • Expression of SGLT2 has neither been detected in human atrial, nor ventricular myocardium
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC8835896/



Hypokalemie



Hypoxie srdce



Lipopolysaccharide (LPS) - leaky gut syndrome

  • Endotoxin outer layer of Gram-negative bacteria
  • Translocation of LPS into the systemic circulation
    • Increased gut permeability
  • Linked to hypertension and atherosclerosis in human studies
  • AF, animal studies
    • LPS assoc. with atrial arrhythmogenesis
  • Intraperitoneal injection of LPS into rats
    • Associated with downregulation of L-type calcium channel gene expression
    • Atrial effective refractory period shortening
    • Unstable atrial response to programmed electrical stimulation
  • Chen et al. showed that LPS treatment in a canine model
    • Led to activation of nuclear factor kB (NF-kB),
    • Increase in plasma and atrial concentrations of proinflammatory markers
    • Increasing connexion 43 expression and lateralisation
      • Led to atrial effective refractory period shortening and inducible AF
  • Ageing and a high-fat diet
    • Can alter the gut microbiota
    • Promote LPS production
  • Group of young rats underwent transplantation of faecal microbiota from an older rats group with increased AF susceptibility
    • Transplanted young rats cohort had a dramatic increase in circulating
      • LPS concentration, glucose, upregulation of NLRP3 inflammasome,
      • Atrial fibrosis,
      • Subsequently inducible AF
  • Kong et al. showed that transplantation of faecal microbiota from mice that had been fed a high-fat diet
    • To a group of mice on a normal diet
    • Led to a significance increase in LPS concentrations
    • Increased inflammatory cytokines,
    • Upregulation of NF-kB and NLRP3 inflammasome activity
    • And AF inducibility
  • In human studies, microbes involved in LPS synthesis
    • Were enriched in the gut of AF patients
    • Associated with an upregulation of LPS synthesis
      • By encoding the LPS-enzymatic biosynthesis gene

Mg deficit



NHE-1 enhanced activity

  • Linked to the increase of late INa and Na+ influx
    • Can prolong action potential duration (APD)
      • Increase the likelihood of early afterdepolarizations (EADs)
  • Activation of NHE1 can also lead to
    • Increased cytosolic Ca2+ concentration
      • Activating Na+/Ca2+ exchanger (NCX) on sarcolemma or mitochondria respectively
  • Activation of the sarcolemmal NCX
    • Promote triggered activity by generating delayed afterdepolarizations (DADs)
  • Activation of the mitochondrial NCX
    • Can elevate the production of reactive oxygen species (ROS) by mitochondria
  • Elevated ROS
    • Promote additional electrical and contractile remodeling
      • By modifying the function of ion channels and Ca2+ handling proteins
      • Activating NOD-like receptor 3 (NLRP3) inflammasome
        • Contributes to the pathogenesis of atrial fibrillation
  • link.springer.com/article/10.1007/s10557-024-07543-7


Nrf2 deficiency

  • Can lead to dysregulation of cardiomyocytes under oxidative stress and increased sympathetic excitability
  • Therefore, applying dietary restrictions or implementing some drug interventions can induce the regulation of Nrf2/ARE and increase the expression of antioxidant enzymes, such as GSH.
  • www.nature.com/articles/s41420-022-01031-3


Trimethylamine N-oxide (TMAO)

  • Gut microbial-derived metabolite
  • Play a role in the pathogenesis of AF
  • Derived from dietary choline or L-carnitine
    • Through gut microbiota
    • Transforms choline to trimethylamine
      • A gas absorbed into the circulation
      • Further converted into TMAO by flavin-containing monooxygenases in the liver
  • TMAO levels in the blood
    • Can be measured using LC-MS
    • Fasting plasma normal range in healthy individuals reported to have a median level of 3.45 uM (IQR: 2.25–5.79 uM)

Several cohort and systematic review studies

  • Linked TMAO with hypertension, obesity, heart failure and coronary artery disease
  • May enhance the development of atherosclerosis
  • AF incidence of 10.9% during a 7-year follow-up
    • Correlated with higher baseline TMAO levels
    • Prospective association was independent of traditional AF risk factors (age, gender, smoking, hypertension, BMI and diabetes)
  • Büttner et al. noted similar TMAO plasma levels between AF and non-AF individuals
    • When individuals with coronary artery disease were excluded
  • Nguyen et al. detected a significant association between TMAO levels and AF clinical phenotype
    • 78 patients
    • TMAO levels were significantly higher in 22 patients with persistent AF
    • Compared with 56 patients with paroxysmal AF
    • Study did not adjust for the traditional risk factors of AF that are known to cause AF
  • Number of studies did not find such an association
  • Cohort of 45 AF patients and 20 healthy matched controls
    • Baseline TMAO levels were similar
    • Did not differ between paroxysmal or persistent AF or healthy controls
  • Follow-up analysis of the PREDIMED study
    • no association between AF and TMAO levels was found
    • Did find an association between baseline plasma choline, betaine and dimethylglycine levels and the risk of incident AF and heart failure.
  • Animal studies have highlighted a range of possible mechanisms that link TMAO with AF
    • Cardiac autonomic nervous system activation
    • Inflammation,
    • Oxidative stress,
    • Endothelial dysfunction
    • Myocardial fibrosis
  • Canine model, Yu et al. demonstrated
    • Activation of inflammatory pathways by TMAO
    • Leading to increased autonomic activity and AF induction
  • TMAO was injected into four major anterior right ganglionated plexi,
    • Resulting in acute electrical remodelling compared with saline controls
    • Associated with a significant increase of the proinflammatory factors interleukin (IL)-1b, IL-6 a TNFa
  • TMAO on atrial tissue in a cohort of rabbit hearts
    • TMAO promoted proliferation and migration of atrial fibroblasts by activating the b-catenin pathway
  • Neonatal rat cardiomyocytes exposed to TMAO
    • Increase in mRNA and protein levels of hypertrophy markers
    • Natriuretic peptide and beta-myosin heavy chain
    • More fibrosis via unregulated transforming growth factor

And treatment of a mouse model with TMAO led to induction or acceleration of vascular age, as measured by an upregulation of senescence markers, including senescence-associated B-galactosidase.44

Short-chain Fatty Acids
Short-chain fatty acids (SCFAs) are metabolites produced by gut microbiota ingestion of dietary fibre. Acetate, propionate and butyrate are the most important and biologically active, accounting for 95% of SCFAs.45 SCFAs have a beneficial immunomodulatory effect on the host through a range of mechanisms.46–48 Zhang et al. recently studied the differences in the microbial genes involved in SCFA-related synthesis in a Chinese cohort.49 AF patients, compared with non-AF patients, had a marked reduction in their SCFA-producing microbes and genes. However, the evidence that links SCFAs to AF is currently limited and most available evidence links it with the progression of traditional AF risk factors such as hypertension, obesity and atherosclerosis. In a mouse model, Kasahara et al. demonstrated that colonising mice gut with butyrate-producing bacteria species (Roseburia sp.) was associated with reduction in endotoxaemia and atherosclerosis development.50 A high-fibre diet and acetate supplementation was associated with reduction in blood pressure and downregulation of the genes associated with the development of cardiac hypertrophy, cardiorenal fibrosis and inflammation.51

Tryptophan

  • Essential amino acid
  • Dietary tryptophan is metabolised into indole
    • By intestinal microbiota
    • Absorbed into the bloodstream
    • Converted to indoxyl sulfate in the liver
  • Indoxyl sulfate is a uremic toxin
    • Associated with cardiovascular adverse effects in patients with chronic kidney disease
  • Rabbit experimental model
    • Increased pulmonary vein and left atrial arrhythmogenesis
    • Reduced sinoatrial pacemaker activity
      • By causing oxidative stress
      • Dysregulation of cardiomyocyte calcium handling
  • Injection of indole sulfate into a rat model
    • Led to stimulation of fibroblasts and cardiomyocytes
    • Increased collagen synthesis
    • Myocyte hypertrophy
    • Increase in proinflammatory cytokines
  • In human studies, elevated indoxyl levels at baseline
    • Associated with an increased risk of AF recurrence after ablation
  • Successful catheter ablation
    • Was associated with a decrease in indoxyl sulphate levels during follow-up
    • Independently associated with an improvement in estimated glomerular filtration rate
      • Suggesting that this would be a mechanism for indoxyl sulfate reduction rather than AF itself
  • www.aerjournal.com/articles/gut-microbiota-and-atrial-fibrillation-pathogenesis-mechanisms-and-therapies

Vitamin D (VitD) deficiency

  • May be one of the critical factors influencing the onset of AF
  • Especially in the period after cardiac surgery
    • Coronary artery bypass grafting

VitD supplementation

  • Reduces the risk of AF
  • Significantly reducing the proportion of patients between the control and study groups in both the pre- and postoperative periods

Factors that increase the risk of AF from VitD deficiency

  • Age, gender, weight, season or comorbidities
  • Cardiodepressive mechanism of VitD is not fully understood
  • Acts through at least two pathways
    • Direct effect of VitD on atrial muscle degradation
    • Modulation of cardiovascular depression factors
  • Correlations between no VitD concentrations on the development of AF
  • Correlation between VitD deficiency and the development of AF associated
    • Mainly with the postoperative period
  • pubmed.ncbi.nlm.nih.gov/37375629/

Vitamin D and new-onset atrial fibrillation: A meta-analysis of randomized controlled trials


Gut Microbiota Changes are Associated with AF

  • Number of observational and small cohort studies have identified distinct gut microbiota features in AF individuals
  • Dramatic alterations in the microbial diversity with a specific perturbation of gut microbiota composition
    • In AF compared with control individuals

In patients with AF:

  • Overgrowth of
    • Ruminococcus,
    • Streptococcus
    • Enterococcus
  • Reduction of
    • Faecalibacterium,
    • Alistipes,
    • Oscillibacter
    • Bilophila

Tabata et al. showed that such alterations are related to

  • Dietary habits when 34 AF patients were compared with 66 controls
    • A depletion in Enterobacter species
    • Enrichment in Parabacteroides, Lachnoclostridium, Streptococcus and Alistipes was observed in AF patients
  • Corresponded to an increase in intake of
    • N-3 polyunsaturated fatty acids and eicosadienoic acid in AF individuals
  • Gut dysbiosis was associated with
    • Progression and duration of AF

Zuo et al. examined the microbial diversity and metabolite composition

  • Patients with paroxysmal AF, persistent AF and individuals without AF
  • Decreased abundance of Butyricicoccus and Paraprevotella
  • Increased abundance of Blautia, Dorea and Coprococcus in persistent AF patients
  • Persistent AF may be related to the imbalance of gut microbiota
  • Changes to the enrichment of intestinal microbes were observed after AF ablation compared with before ablation
    • Enrichment in beneficial bacteria
    • Reduction in pathogenic bacteria
    • Corresponding change in metabolite levels
  • Causal relationship between AF and gut microbiota remains unclear

Xu et al. showed in a bidirectional Mendelian randomisation analysis using a Chinese cohort


Iron deficiency



Kawasaki disease (KD)

  • Systemic vasculitis
  • Often associated with cardiac sequelae, including arrhythmias
  • IL-1 and TNFa in the formation of arterial lesions in KD.

Lactobacillus casei cell wall extract-induced KD vasculitis mice model was used

  • KD vasculitis was associated with impaired ejection fraction, increased ventricular tachycardia, prolonged repolarization, and slowed conduction velocity.
  • Only inhibition of IL-1 signaling by IL-1Ra but not TNF? neutralization
    • Was able to prevent changes in ejection fraction and arrhythmias
  • Both IL-1Ra and TNF? neutralization
    • Significantly improved vasculitis and heart vessel inflammation
  • IL-1Ra also restored conduction velocity and improved the organization of Cx43 (connexin 43) at the intercalated disk
  • Mice with gain of function of the IL-1 signaling pathway
    • Induced spontaneous ventricular tachycardia and premature deaths.
  • pubmed.ncbi.nlm.nih.gov/38385289/

Magnesium deficiency



Overactive enzymes:



Oxidační stres



Selen deficit

  • Selenium, iron, and magnesium deficiency
    • Observed in 1155 (21.2%), 797 (14.6%), and 3600 (66.0%) participants
  • Follow-up of 6.2 years
    • 136 (2.5%) participants developed new-onset AFib
    • Smoking status significantly interacted with selenium deficiency on outcome (p = 0.079).
  • selenium deficiency was associated with new-onset AFib in non-smokers
    • (HR 1.69, 95% CI 1.09-2.64, p = 0.020),
  • But not in smokers
    • (HR 0.78, 95% CI 0.29-2.08, p = 0.619).
  • pubmed.ncbi.nlm.nih.gov/37589740/


Spánková apnoe



Vit. C deficit



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Poslední aktualizace: 24. 4. 2024 2:24:40