Association of atrial arrhythmias with thrombospondin-1 in patients with acute myocardial infarction.

OBJECTIVES: Atrial remodeling is the main developmental cause of atrial arrhythmias (AA), which may induce atrial fibrillation, atrial flutter, atrial tachycardia, and frequent premature atrial beats in acute myocardial infarction (AMI) patients. Thrombospondin-1 (TSP-1) has been shown to play an important role in inflammatory and fibrotic processes, but its role in atrial arrhythmias is not well described. The purpose of this study was to investigate the role of TSP-1 in AMI patients with atrial arrhythmias. METHODS: A total of 219 patients with AMI who underwent percutaneous coronary intervention and with no previous arrhythmias were included. TSP-1 were analyzed in plasma samples. Patients were classified into 2 groups, namely, with and without AA during the acute phase of MI. Continuous electrocardiographic monitoring was used for AA diagnosis in hospital. RESULTS: Twenty-four patients developed AA. Patients with AA had higher TSP-1 levels (29.01 ± 25.87 µg/mL vs 18.36 ± 10.89 µg/mL, p < 0.001) than those without AA. AA patients also tended to be elderly (65.25 ± 9.98 years vs 57.47 ± 10.78 years, p < 0.001), had higher Hs-CRP (39.74 ± 43.50 mg/L vs 12.22 ± 19.25 mg/L, p < 0.001) and worse heart function. TSP-1 (OR 1.033; 95% CI 1.003-1.065, p = 0.034), Hs-CRP (OR 1.023; 95% CI 1.006-1.041, p = 0.008), age (OR 1.067; 95% CI 1.004-1.135, p = 0.038) and LVDd (OR 1.142; 95% CI 1.018-1.282, p = 0.024) emerged as independent risk factors for AA in AMI patients. CONCLUSION: TSP-1 is a potential novel indicator of atrial arrhythmias during AMI.

Supraventricular arrhythmia, N-terminal pro-brain natriuretic peptide and troponin T concentration in relation to incidence of atrial fibrillation: a prospective cohort study.

BACKGROUND: Frequent supraventricular arrhythmia is associated with increased incidence of atrial fibrillation. However, it is unknown whether the prognostic significance of supraventricular arrhythmia is modified by plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) or troponin T (TnT). This study examined the interrelationships between NT-proBNP, TnT levels and frequent supraventricular arrhythmia, and whether these biomarkers and a measure of frequent supraventricular arrhythmia could improve risk assessment for incidence of AF. METHODS: Supraventricular extrasystoles (SVEs) and supraventricular tachycardias were assessed from 24-h electrocardiograph recordings in 373 individuals initially without AF. Elevated NT-pro-BNP, TnT and SVEs was defined as a measurement in the top quartile of the study population distribution. Incident cases of AF were retrieved by linkage with the Swedish National Patient Register. RESULTS: During a mean follow-up of 15.4 years, 88 subjects had a diagnosis of AF. After multivariable adjustment, individuals with both elevated NT-proBNP and frequent SVEs had a significantly increased incidence of AF, compared to subjects without elevated NT-proBNP or frequent SVEs (hazard ratio (HR) 4.61, 95% confidence interval (CI) 2.45-8.69), and compared to individuals with either elevated NT-proBNP or frequent SVEs (both P < 0.05). HRs for frequent SVEs alone or elevated NT-proBNP alone were 2.32 (95% CI 1.33-4.06) and 1.52 (95% CI 0.76-3.05), respectively. The addition of NT-pro-BNP and SVEs to a validated risk prediction score for AF, CHARGE-AF, resulted in improved prediction (Harrell's C 0.751 (95% CI 0.702-0.799) vs 0.720 (95% CI 0.669-0.771), P = 0.015). CONCLUSION: Subjects with both elevated NT-proBNP and frequent SVEs have substantially increased risk of AF, and the use of these variables could improve long-term prediction of incident AF.

Circulating electrolytes and the prevalence of atrial fibrillation and supraventricular ectopy: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND AIMS: Evaluating associations of circulating electrolytes with atrial fibrillation (AF) and burden of supraventricular arrhythmias can give insights into arrhythmia pathogenesis. METHODS AND RESULTS: We conducted a cross-sectional analysis of 6398 participants of the Atherosclerosis Risk in Communities (ARIC) study, ages 71-90, with data on serum electrolytes (magnesium, calcium, potassium, phosphorus, chloride, sodium). Prevalence of AF was determined from electrocardiograms and history of AF hospitalizations. A subset of 317 participants also underwent electrocardiographic recordings for up to 14 days using the Zio® patch. Burden of other supraventricular arrhythmias [premature atrial contractions (PACs), supraventricular tachycardia] was determined with the Zio® patch. We used logistic and linear regression adjusting for potential confounders to determine associations of electrolytes with arrhythmia prevalence and burden. Among 6394 eligible participants, 614 (10%) had AF. Participants in the top quintiles of magnesium [odds ratio (OR) 0.82, 95% confidence interval (CI) 0.62, 1.08], potassium (OR 0.82, 95%CI 0.68, 1.00), and phosphorus (OR 0.73, 95%CI 0.59, 0.89) had lower AF prevalence compared to those in the bottom quintiles. No clear association was found for circulating chloride, calcium or sodium. Higher concentrations of circulating calcium were associated with lower prevalence of PACs in the 12-lead electrocardiogram, while higher concentrations of potassium, chloride and sodium were associated with higher PAC prevalence. Circulating electrolytes were not significantly associated with burden of PACs or supraventricular tachycardia among 317 participants with extended electrocardiographic monitoring. CONCLUSION: Concentrations of circulating electrolytes present complex associations with selected supraventricular arrhythmias. Future studies should evaluate underlying mechanisms.

Circulating primary bile acid is correlated with structural remodeling in atrial fibrillation.

BACKGROUND: Circulating primary bile acid was involved in the regulation of cardiac ionic channel currents and ventricular myocyte apoptosis, but it was unknown whether or not it played a role in structural remodeling of AF. This study was aimed to testify the hypothesis that elevated chenodeoxycholic acid (CDCA) concentration correlated with left atrial low voltage area (LVA) and could induce apoptosis of atrial myocytes in AF. METHODS AND RESULTS: Serum concentrations of 12 types of bile acids were determined in patients with paroxysmal (n = 21), persistent AF (n = 20), and type A pre-excitation and paroxysmal supraventricular tachycardia (PSVT) (n = 19) and were correlated with LVA in AF, which was obtained by electroanatomical mapping during ablation. Additionally, the impact of CDCA incubation on apoptosis of mouse atrial myocytes was evaluated. Serum levels of CDCA and cholic acid were significantly higher in AF than in PSVT. CDCA serum concentration was significantly higher in persistent AF than in paroxysmal AF. CDCA serum level was positively correlated with the size (r = 0.78, P < 0.05) and proportion of LVA (r = 0.89, P < 0.05) in AF patients. CDCA (75 µM, 100 µM) promoted atrial myocyte apoptosis in a concentration-dependent manner. CONCLUSIONS: The higher circulating level of CDCA in AF than in PSVT, positive correlation of CDCA with LVA in AF, and incubation dose-dependent increase of mouse atrial myocyte apoptosis indicated that CDCA might play a significant role in the progress of structural remodeling of AF.

Expression of miRNAs in circulating exosomes derived from patients with persistent atrial fibrillation.

Atrial fibrillation (AF), the most common type of cardiac arrhythmia, is thought to be regulated by changes in microRNA (miRNA) expression. However, the evidence for this is inconsistent. The high stability and expression of circulating exosomal miRNAs may allow their use as candidate biomarkers. For the discovery phase, exosomes were isolated from the serum of patients with supraventricular tachycardia (SVT) as the controls (n = 5) and with paroxysmal AF (n = 4) and persistent AF (n = 5) for microarray analysis of miRNAs. Forty-five miRNAs were expressed significantly higher (>1.5-fold) in patients with persistent AF, but not in patients with paroxysmal AF, relative to the levels in patients with SVT control. Notably, expression of 5 miRNAs (miRNA-103a, -107, -320d, -486, and let-7b) was elevated by more than 4.5-fold in patients with persistent AF. For the validation phase, miRNAs were analyzed using quantitative RT-PCR analysis in exosomes from the serum of patients with SVT control (n = 20) and patients with persistent AF (n = 40). These miRNAs and their target genes were involved in atrial function and structure, oxidative stress, and fibrosis pathways. These findings suggest that serum exosomal miRNAs might be used as novel biomarkers to reflect the progression of AF.-Mun, D., Kim, H., Kang, J.-Y., Park, H., Park, H., Lee, S.-H., Yun, N., Joung, B. Expression of miRNAs in circulating exosomes derived from patients with persistent atrial fibrillation.

Review article: The utility of troponin and other investigations in patients presenting to the emergency department with supraventricular tachycardia.

Patients with supraventricular tachycardia commonly present to the ED. There is a lack of consensus regarding assessment of these patients. Our aim was to determine the utility of troponin and four other investigations (full blood examination, electrolyte levels, thyroid function tests and chest X-rays) commonly requested for these patients. MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (January 1992-March 2017) were searched for randomised controlled trials and observational studies (of sample size greater than 10). Our search strategy yielded no randomised controlled trials and seven observational studies with significant statistical heterogeneity among selected studies (I2 87.3%, P < 0.001). Included studies investigated a total of 1155 patients. All studies reported on the utility of troponin testing in this patient population. The pooled proportion of patients investigated with troponin was 0.66 (95% confidence interval 0.44-0.88). The pooled proportion of positive troponin tests was 0.32 (95% confidence interval 0.23-0.41). Only one study reported on the utility of the remaining four investigations with abnormal results as follows: thyroid stimulating hormone 14%, haemoglobin 6%, white cell count 19% and chest X-ray 22%. Investigations are commonly requested for patients presenting with supraventricular tachycardia. Troponin testing is commonly performed with a high proportion of positive findings although these results did not appear to be associated with major adverse cardiac events. Heterogeneity among studies and low levels of evidence precluded conclusions on full blood examinations, electrolyte levels, thyroid testing and utility of chest X-rays in this patient population.

Supraventricular tachycardia during the first year of life: is subclinical inflammation the trigger?

BACKGROUND: Neutrophil/lymphocyte ratio (NLR) and red cell distribution width (RDW) may be associated with the onset of arrhythmias in adults, thus underlining a possible inflammatory etiology. Paroxysmal supraventricular tachycardia (SVT) is the most frequent pathological tachycardia in childhood. AIM: To verify NLR and RDW levels in a group of children (<1 year) affected by SVT with a structurally normal heart and without fever or inflammatory diseases; to compare NLR and RDW before and after SVT resolution, to verify whether the latter was related with the reduction in inflammatory state; to identify - in SVT subtypes caused by a reentry mechanism - an NLR and RDW cutoff point beyond which adenosine was ineffective in preventing SVT recurrence. METHODS: Eighteen SVT patients were recruited (mean age 18.9 ± 3.2 days; 50% males) and compared with 18 healthy peers. RESULTS: NLR was higher in SVT group than in controls (p < 0.03). A significant difference was revealed between NLR values obtained on admission and at discharge (p < 0.05). On the contrary, no significant differences were found for RDW. It was not possible to identify NLR or RDW cutoffs capable of predicting SVT recurrence. However, all patients featuring SVT recurrence following adenosine injection presented with a lymphocyte count >6000/mm3. CONCLUSIONS: Elevated NLR is associated with an increased risk of SVT during the first year of life, while its decline looks like to lead the SVT resolution. A subclinical inflammatory status, as assessed by lymphocytes count, influences SVT recurrence. These results provide further support for an inflammatory etiology of SVT in babies.

Predictors of High-Sensitivity Cardiac Troponin T Elevation in Patients with Acute Paroxysmal Supraventricular Tachycardia and Ischemic Heart Disease.

We studied the predictors and patterns of high-sensitivity cardiac troponin T (hs-cTnT) elevation in patients with paroxysmal supraventricular tachycardia (PSVT) in the presence and absence of ischemic heart disease. During calendar year 2013, we enrolled 70 of 72 consecutive adult patients with PSVT who presented at our center within 4 hours after the onset of tachycardia. On the basis of increased hs-cTnT at either of 2 initial measurements, we divided patients into groups (hs-cTnT-positive and hs-cTnT-negative), to study the predictors of enzyme elevation. We then divided the hs-cTnT-positive patients into 2 groups-those with and those without ischemic heart disease-and compared hs-cTnT changes. We observed hs-cTnT elevation in 52 of the 70 patients (74.3%). The hs-cTnT-positive patients were significantly older (P=0.008) and had a significantly higher duration of tachycardia (P=0.01). Older age, the presence of chest pain, lower diastolic blood pressure, and longer duration of tachycardia increased the odds of enzyme elevation. Among patients with elevated hs-cTnT levels, the baseline and maximal hs-cTnT levels were significantly higher in ischemic patients (P=0.01 and P=0.003, respectively). The increase in hs-cTnT seemed to be higher and longer in ischemic patients, although this was not statistically significant (P=0.908). Finally, hs-cTnT did not decrease to baseline levels within 48 hours in either group. We found that hs-cTnT levels increased in all our patients with PSVT, more so in those with ischemic heart disease.

Intracardiac Hemostasis and Fibrinolysis Parameters in Patients with Atrial Fibrillation.

AIMS: To identify intracardiac hemostasis or fibrinolysis abnormalities, which are associated with atrial fibrillation (AF) and increase the risk of thromboembolism. PATIENTS AND METHODS: Patient group consisted of 24 patients with AF and control group included 14 individuals with other supraventricular tachycardia undergoing transcatheter radiofrequency ablation. Blood samples were drawn from the femoral vein (FV), left atrium (LA), and left atrial appendage (LAA) before the ablation procedure. Fibrinogen, factor VIII (FVIII) and factor XIII activity, von Willebrand factor (VWF) antigen, thrombin-antithrombin (TAT) complex, quantitative fibrin monomer (FM), plasminogen, α2-plasmin inhibitor, plasmin-α2-antiplasmin (PAP) complex, PAI-1 activity, and D-dimer were measured from all samples. RESULTS: Levels of FVIII and VWF were significantly elevated in the FV and LA of AF patients as compared to controls. TAT complex, FM, PAP complex, and D-dimer levels were significantly elevated in the LA as compared to FV samples in case of both groups, indicating a temporary thrombotic risk associated with the catheterization procedure. CONCLUSIONS: None of the investigated hemostasis or fibrinolysis parameters showed significant intracardiac alterations in AF patients as compared to non-AF controls. AF patients have elevated FVIII and VWF levels, most likely due to endothelial damage, presenting at both intracardiac and systemic level.

[Clinical aspects of treatment with amiodarone]. / Klinische Besonderheiten der Therapie mit Amiodaron.

Amiodarone has multiple and complex electrophysiological effects that render it a very effective antiarrhythmic drug for the treatment of both, supraventricular and ventricular arrhythmias. Proarrhythmic effects of amiodarone in patients with structural heart disease are rare. However, extracardiac adverse effects occurring in association with amiodarone treatment are frequent and feared. These adverse effects have usually been related to total amiodarone exposure (i. e., dose and duration of treatment). Parallel to a more frequent use of lower amiodarone maintenance doses (100-200 mg/day), the incidence of severe unwanted extracardiac side effects has decreased. High-dose maintenance regiments (daily dose ≥300 mg) are usually obsolete. This paper discusses recommendations regarding the monitoring of cardiac and extracardiac side effects of amiodarone. They need to be regarded by physicians using amiodarone to ensure long-term safety of amiodarone therapy.

Elevated high-sensitivity troponin does not indicate the presence of coronary artery disease in patients presenting with supraventricular tachycardia.

BACKGROUND: Patients with supraventricular tachycardia (SVT) and patients with coronary artery disease (CAD) often present with similar symptoms (chest pain, shortness of breath), similar electrocar¬diographic changes and elevated high-sensitivity troponin (Tn). It is not clear whether troponin reflects critical CAD or is elevated due to other causes in patients presenting with SVT. The aim of this study was to assess the role of elevated troponin in patients presenting with SVT. METHODS: Patients undergoing radiofrequency ablation (RFA) for SVT and simultaneous coronary an¬giography at the Heart Centre Lucerne, Switzerland between January 2010 and October 2014 were in¬cluded in this analysis. Significant CAD was defined as diameter-stenosis ≥ 75% in vessels > 2.0 mm. The level of Tn was compared between patients with the presence or absence of CAD on coronary angi¬ography. A Tn value of ≥ 0.014 µg/L was considered as elevated. RESULTS: During the study period a total of 473 patients underwent RFA for SVT. The study population consisted of 326 patients (69%, mean age 60 ± 12 years) who underwent invasive coronary angiogra¬phy during the same session. The prevalence of significant CAD was 14% (45/326 patients). The highest prevalence of CAD was found in patients with atrial flutter (35%, 18/45 patients). Tn was elevated in 83% (10/12 patients) with significant CAD and in 47% (26/55 patients) without CAD. CONCLUSIONS: The prevalence of CAD is low in patients with SVT, which questions the role of routine invasive coronary angiography during RFA. Tn measurement did not reliably exclude or confirm CAD in these patients.

Premature Ventricular Complex is More Prevalent During Acute Exacerbated than Stable States of Chronic Obstructive Pulmonary Disease, and Is Related to Cardiac Troponin T.

During acute exacerbation of chronic obstructive pulmonary disease (AECOPD), myocardial stress may be aggravated. Sparse data exist concerning the prevalence and correlates of cardiac arrhythmias in the stable and exacerbated states of COPD. We hypothesized that AECOPD is associated with increased prevalence of cardiac arrhythmias independent of COPD-severity and co-morbidity, and explored possible mechanisms. A 24-hour Holter recording was obtained in 74 patients with stable COPD and 45 patients with AECOPD (mean age 54 years, 56% women). Any incidence of supraventricular tachycardia (SVT), frequent premature ventricular complex (PVC, >30/hour) and complex ventricular ectopy (bigeminy, trigeminy or non-sustained ventricular tachycardia) was recorded and compared between the two groups. Adjustments were made for by stable disease-related co-variates (demography, co-morbidity, COPD-severity) and by acute disease-related co-variates (heart rate, cardiac troponin T (cTnT), PO2, PCO2 and C-reactive protein (CRP)) in explorative analyses. The prevalence of SVT, frequent PVCs or complex ventricular ectopy was 40%, 27% and 33% in AECOPD, and 31%, 31% and 12% in stable COPD, respectively. Frequent PVC, but not SVT or complex ventricular ectopy, was significantly increased in AECOPD compared to stable COPD, odds ratio 3.03 (1.03-10.5, p = 0.039) when adjusted for stable disease-related co-variates. Higher heart rate, cTnT and CRP attenuated the association between AECOPD and frequent PVC to non-significant, while heart rate remained associated with frequent PVC. In conclusion, frequent PVC is more prevalent in exacerbated than in the stable states of COPD. Attenuation effects of cTnT, tachycardia and CRP suggest that cardiac stress or inflammation may be involved in mechanisms causing frequent PVC i AECOPD.

When potion becomes poison! A case report of flecainide toxicity.

We report a 48-day-old female infant, who developed cardiac conduction abnormalities and seizures secondary to supratherapeutic doses of oral flecainide. Flecainide was started in this infant for treatment of supraventricular tachycardia. The drug was withdrawn with successful normalization of the QRS complex and no further recurrence of seizures. The Naranjo probability score for adverse drug reaction was 8, making the causality "probable." The case restates an important message that physicians should be aware of the side effects of the drugs that they prescribe, especially of those drugs which have a narrow therapeutic window.

High-Sensitivity Cardiac Troponin Levels in Supraventricular Tachyarrhythmias.

BACKGROUND: High-sensitivity cardiac troponin assays have provided a significant contribution for the early diagnosis of cardiovascular events. However, elevated cardiac troponin levels may occur in other clinical situations as supraventricular tachyarrhythmias with concerns about the mechanism of this elevation. OBJECTIVES AND METHODS: The goal of this study was to describe the performance of high-sensitivity cardiac troponin T (hs-cTnT) assay in patients presenting to the emergency department with a primary diagnosis of supraventricular tachyarrhythmia and to evaluate its relation with cardiovascular events during follow-up. RESULTS: One hundred patients were included; mean age was 64 ± 12 years and 59.8% were men. The most common arrhythmia at admission was atrial fibrillation (68%), followed by atrial flutter (16%) and reentrant tachycardia (16%). The results of the first determination of hs-cTnT were positive (>14 ng/L) in 44.2% of the patients and the second determination was positive in 50.7% of the cases. The variation between the first and the second troponin levels was 1 (0-5) ng/L, and was >7 ng/L in 24.6% of the cases, with a clear trend toward higher troponin values in reentrant tachycardias. Four events were reported at 30 days; in all the cases the patients had presented atrial fibrillation and there were no significant differences in hs-cTnT values. CONCLUSIONS: There are a significant number of patients with supraventricular tachyarrhythmias who present elevated hs-cTnT levels. The association of this elevation with cardiovascular events seems to be very low.

Responses of cardiac natriuretic peptides after paroxysmal supraventricular tachycardia: ANP surges faster than BNP and CNP.

Atrial natriuretic peptide (ANP) secretion increases after 30 min of paroxysmal supraventricular tachycardia (PSVT). Whether this phenomenon also applies to brain or C-type natriuretic peptides (BNP or CNP) remains unknown. Blood samples of 18 patients (41 ± 11 yr old; 4 men) with symptomatic PSVT and normal left ventricular systolic function (ejection fraction 65 ± 6%) were collected from the coronary sinus (CS) and the femoral artery (FA) before and 30 min after the induction, and 30 min after the termination of PSVT. The results showed that the ANP levels rose steeply after the PSVT and then reduced at 30 min after the termination (baseline vs. post-PSVT vs. posttermination: CS: 34.0 ± 29.6 vs. 74.1 ± 42.3 vs. 46.1 ± 32.9; FA: 5.9 ± 3.24 vs. 28.2 ± 20.7 vs. 10.0 ± 4.6 pg/ml; all P < 0.05). In contrast, compared with ANP, the increases of BNP and CNP in CS after the PSVT were less sharp, but continued to rise after the termination of tachycardia (BNP, 10.2 ± 6.4 vs. 11.3 ± 7.1 vs. 11.8 ± 7.9; CNP, 4.5 ± 1.2 vs. 4.9 ± 1.4 vs. 5.0 ± 1.4 pg/ml; all P < 0.05). The rise of BNP and CNP in FA was similarly less sharp after the PSVT and remained stationary after the termination. PSVT exerted differential effects on cardiac natriuretic peptide levels. ANP increased greater after a 30-min induced PSVT, but dropped faster after termination of PSVT, compared with BNP and CNP.

Characterization of Cardiac Troponin Elevation in the Setting of Pediatric Supraventricular Tachycardia.

Cardiac troponin (cTn) is currently considered the gold standard biomarker for detection of myocardial necrosis. Patients with supraventricular tachycardia (SVT) often present with symptoms resulting in cTn assessment; however, there are no data on the results of such testing in childhood. We hypothesized that cTn elevation would be common in the pediatric SVT population and would portend a benign prognosis. A retrospective review of all pediatric patients (≤21 years) presenting with SVT was performed. Clinical and electrocardiographic variables from the emergency department (ED) presentation were reviewed and clinical outcomes during subsequent follow-up assessed. Of 128 patients seen in the ED for SVT, cTn was assessed in 48 (38 %). Of patients with cTn assessment, 14 (29 %) patients demonstrated cTn elevation. Univariate predictors of cTn elevation included presentation with respiratory or gastrointestinal symptoms (50 vs 12 % and 42 vs 9 %; p = 0.008 and p = 0.01, respectively), lower mean arterial blood pressure (73 vs 85 mm Hg, p = 0.009), higher age-adjusted tachycardia rate (z score 9.3 vs 7.2, p < 0.001), and longer tachycardia duration (4.2 vs 1.0 h, p = 0.02). Multivariate logistic regression confirmed the association of age-adjusted tachycardia rate (odds ratio [OR] 3.8 per heart rate z score, confidence interval [CI] 1.9-11.8, p = 0.003) and duration (OR 1.5 per hour, CI 1.1-2.5, p = 0.03). Clinical outcome was excellent with no adverse sequelae during a median of 2.9 years of follow-up. Cardiac Tn elevation is common in the pediatric population presenting with SVT. Episode severity, characterized by respiratory or gastrointestinal symptoms, lower mean blood pressure, and increased tachycardia rate and duration are predictive. Clinical follow-up is favorable.

Assessment of the neutrophil/lymphocyte ratio in patients with supraventricular tachycardia.

OBJECTIVE: The neutrophil/lymphocyte ratio (NLR) has been evaluated as a new predictor of cardiovascular risk. Inflammation has been shown to be associated with various arrhythmias including supraventricular tachycardias (SVTs). In this study, we aimed to investigate the relation between NLR and SVT in patients with a documented atrial tachyarrhythmia. METHODS: The study used a retrospective cross-sectional design. Patients who had SVT but were otherwise healthy were included. The exclusion criteria included drug use (except antiarrhythmic agents), morbid obesity, acute or chronic infection, inflammatory diseases, systemic diseases, and cancer. Total and differential leukocyte counts and routine biochemical tests were performed before the ablation procedure. RESULTS: The study included 150 patients with SVT and 98 healthy controls. The biochemical and hematological parameters were comparable between the groups, except neutrophil and lymphocyte counts. The neutrophil count was significantly higher (4.7±1.5x103/µL versus 4.1±1.0x103/µL; p<0.001) and lymphocyte count was significantly lower (2.2±0.6x103/µL versus 2.5±0.6x103/µL; p=0.001) in the SVT group than in the control group. As a result, the SVT group had significantly higher NLR values than the control group (2.2±0.9 versus 1.7±0.5; p<0.001). In addition, NLR values were higher in patients in whom tachycardia was induced during an electrophysiological study (EPS) (2.3±0.9 versus 2.0±0.8; p=0.02). The association between NLR and SVT remained significant after multivariate analysis (odds ratio: 1.5, 95% confidence interval: 1.001-2.263, p=0.049). CONCLUSION: Our study indicated that NLR values were significantly higher in patients with documented SVT than in control subjects. Inducibility of SVT during EPS was associated with higher NLR values.

Serum flecainide S/R ratio reflects the CYP2D6 genotype and changes in CYP2D6 activity.

The aims of this study were to clarify whether the ratio of S- to R-flecainide (S/R ratio) in the serum flecainide concentration was associated with the stereoselectivity of flecainide metabolism, and to investigate the effects of the cytochrome P450 (CYP) 2D6 (CYP2D6) genotype and CYP2D6 inhibitor on the serum flecainide S/R ratio. In vitro studies using human liver microsomes and cDNA-expressed CYP isoforms suggested that variability in the serum flecainide S/R ratio was associated with the stereoselectivity of CYP2D6-mediated flecainide metabolism. We examined the serum flecainide S/R ratio in 143 patients with supraventricular tachyarrhythmia. The S/R ratio was significantly lower in intermediate metabolizers and poor metabolizers (IMs/PMs) than in extensive metabolizers (EMs) identified by the CYP2D6 genotype. The cut-off value for the S/R ratio to allow the discrimination between CYP2D6 EMs and IMs/PMs was 0.99. The S/R ratio in patients with co-administration of bepridil, a potent CYP2D6 inhibitor, was lower than 0.99, regardless of the CYP2D6 genotype status. Other factors, including age, sex, body weight, and renal function, did not affect the serum flecainide S/R ratio. This study suggests that the serum flecainide S/R ratio reflects the CYP2D6 genotype and changes in CYP2D6 activity on co-administration of a CYP2D6 inhibitor.