Computed tomography-based measurements associated with rapid lung function decline in severe asthma.

BACKGROUND: Patients with severe asthma are susceptible to lung function decline (LFD), but biomarkers that reliably predict an accelerated LFD have not been fully recognized. OBJECTIVE: To identify variables associated with previous LFD occurrences in patients with severe asthma by exploring the computed tomography (CT) imaging features within predefined LFD groups. METHODS: We obtained inspiratory and expiratory CT images of 102 patients with severe asthma and derived 2 airway structural parameters (wall thickness [WT] and hydraulic diameter) and 2 parenchymal variables (functional small airway disease and emphysema). We retrospectively calculated the annual changes in forced expiratory volume in 1 second and grouped participants by their values determined. The 4-imaging metrics, along with levels of several biomarkers, were compared among the LFD groups. RESULTS: Patients with severe asthma with enhanced LFD exhibited significantly lower WT and smaller hydraulic diameter compared with those with minimal change or slight decline in lung function, after an adjustment of smoking status. Conversely, CT-based percentages of emphysema and functional small airway disease did not significantly differ according to LFD. Furthermore, fractional exhaled nitric oxide (FeNO) level and the blood matrix metalloproteinase-9/TIMP metallopeptidase inhibitor 1 ratio were significantly higher in patients with severe asthma with enhanced LFD compared with those in the others. CONCLUSION: Lower WT on CT scans with increased FeNO that may represent increased airway inflammation significantly correlated with enhanced LFD in patients with severe asthma. Consequently, active management plans may help to attenuate LFD for patients with severe asthma with lower WT and high FeNO.

Comparative Bleeding Risk in Patients with Atrial Fibrillation with Cancer versus Without Cancer from Nationwide Prospective Cohort.

Comparison of the bleeding risk for long-term oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF) with and without cancers has been inconsistent. This study aimed to clarify the differences in the bleeding risk in patients with AF with cancers and those without cancers during the long-term OAC.The CODE-AF prospective registry enrolled 5,902 consecutive patients treated for AF at 10 tertiary referral centers in Korea. Of the enrolled patients, 464 (7.8%) were diagnosed with cancers and were followed for all stroke and bleeding events (net composite events).The age, CHA2DS2-VASC, and HAS-BLED scores were similar between AF patients with and without cancers. Male population greatly comprised patients with AF with cancers. They were equally prescribed with direct OAC compared to those without cancers. The incidence rate for clinically relevant nonmajor (CRNM) bleeding events was higher in the patients with AF with cancers than in those without cancers (4.4 per 100 person-years versus 2.8 per 100 person-years, P = 0.023), and net composite events were also more frequent in patients with AF with cancers than in those without cancers (6.4 per 100 person-years versus 4.0 per 100 person-years, P = 0.004). Patients with AF with cancers showed a significantly higher rate of CRNM bleeding (hazard ratio [HR] 1.54, confidence interval [CI] 1.05-2.25, P = 0.002) than those without cancers.Based on the AF cohort, AF with cancers could face a significantly higher risk for CRNM bleeding events in the long-term OAC than those without cancers.

Effect of alcohol consumption on the risk of adverse events in atrial fibrillation: from the COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry.

AIMS: The aim of this study is to determine the relationship between alcohol consumption and atrial fibrillation (AF)-related adverse events in the AF population. METHODS AND RESULTS: A total of 9411 patients with nonvalvular AF in a prospective observational registry were categorized into four groups according to the amount of alcohol consumption-abstainer-rare, light (<100 g/week), moderate (100-200 g/week), and heavy (≥200 g/week). Data on adverse events (ischaemic stroke, transient ischaemic attack, systemic embolic event, or AF hospitalization including for AF rate or rhythm control and heart failure management) were collected for 17.4 ± 7.3 months. A Cox proportional hazard models was performed to calculate hazard ratios (HRs), and propensity score matching was conducted to validate the results. The heavy alcohol consumption group showed an increased risk of composite adverse outcomes [adjusted hazard ratio (aHR) 1.32, 95% confidence interval (CI) 1.06-1.66] compared with the reference group (abstainer-rare group). However, no significant increased risk for adverse outcomes was observed in the light (aHR 0.88, 95% CI 0.68-1.13) and moderate (aHR 0.91, 95% CI 0.63-1.33) groups. In subgroup analyses, adverse effect of heavy alcohol consumption was significant, especially among patients with low CHA2DS2-VASc score, without hypertension, and in whom ß-blocker were not prescribed. CONCLUSION: Our findings suggest that heavy alcohol consumption increases the risk of adverse events in patients with AF, whereas light or moderate alcohol consumption does not.

Clinical Impact of Implantable Cardioverter-Defibrillator Therapy and Mortality Prediction Model for Effective Primary Prevention in Korean Patients.

BACKGROUND: Studies on the efficacy of implantable cardioverter-defibrillator (ICD) therapy for primary prevention in Asian patients are relatively lacking compared to those for secondary prevention. Also, it is important to stratify which patients will benefit from ICD therapy for primary prevention. METHODS: Of 483 consecutive patients who received new implantation of ICD in 9 centers in Korea, 305 patients with reduced left ventricular systolic function and/or documented ventricular fibrillation/tachycardia were enrolled and divided into primary (n = 167) and secondary prevention groups (n = 138). RESULTS: During mean follow-up duration of 2.6 ± 1.6 years, appropriate ICD therapy occurred in 78 patients (25.6%), and appropriate ICD shock and anti-tachycardia pacing occurred in 15.1% and 15.1% of patients, respectively. Appropriate ICD shock rate was not different between the two groups (primary 12% vs. secondary 18.8%, P = 0.118). However, appropriate ICD therapy rate including shock and anti-tachycardia pacing was significantly higher (primary 18% vs. secondary 34.8%, P = 0.001) in the secondary prevention group. Type of prevention and etiology, appropriate and inappropriate ICD shock did not affect all-cause death. High levels of N-terminal pro-B-type natriuretic peptide, New York Heart Association functional class, low levels of estimated glomerular filtration ratio, and body mass index were associated with death before appropriate ICD shock in the primary prevention group. When patients were categorized in 5 risk score groups according to the sum of values defined by each cut-off level, significant differences in death rate before appropriate ICD shock were observed among risk 0 (0%), 1 (3.6%), 2 (3%), 3 (26.5%), and 4 (40%) (P < 0.001). CONCLUSION: In this multicenter regional registry, the frequency of appropriate ICD therapy is not low in the primary prevention group. In addition, combination of poor prognostic factors of heart failure is useful in risk stratification of patients who are not benefiting from ICD therapy for primary prevention.

Supraventricular tachyarrhythmias in patients with a persistent left superior vena cava.

Aims: A persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly. This venous anomaly can impact the evaluation and treatment of supraventricular tachyarrhythmia (SVA). The aim of this study was to assess the proportion and characteristics of PLSVC in adult SVA patients. Methods and results: From July 2002 to July 2012, clinical and procedural data from databases of 10 cardiac electrophysiology laboratories in the Yeungnam region of the Republic of Korea were reviewed. Of 6662 adult SVA patients who underwent an EP study or catheter ablation of SVA during the 10-year study period, 18 patients had PLSVC (mean age 47.6 ± 14.8 years, 10 men). The proportion of PLSVC in adult SVA patients was 0.27% (18/6662). SVA type and procedural outcomes of radiofrequency (RF) catheter ablation in these patients were investigated and the results were as follows: successful slow pathway modification in six of seven patients with atrioventricular nodal reentrant tachycardia (AVNRT), successful ablation of accessory pathway in three of four patients with atrioventricular reentrant tachycardia, and successful ablation of atrial tachycardia (cavotricuspid isthmus-dependent in two, septal macroreentry in one, focal from the PLSVC in one) in three of four patients. In one patient with junctional tachycardia, catheter ablation failed. In two patients with atrial fibrillation, catheter ablation was successful. Conclusion: Among adult SVA patients who underwent an EP study or RF catheter ablation during the 10-year study period, 0.27% had PLSVC. The most common type of SVA was AVNRT. The success rate of catheter ablation was 82% in SVA patients with PLSVC. There were no procedure-related complications.

Variants of Brugada Syndrome and Early Repolarization Syndrome: An Expanded Concept of J-Wave Syndrome.

BACKGROUND: The role of J-waves in the pathogenesis of ventricular fibrillation (VF) occurring in structurally normal hearts is important. METHODS: We evaluated 127 patients who received an implantable cardioverter-defibrillator (ICD) for Brugada syndrome (BS, n = 53), early repolarization syndrome (ERS, n = 24), and patients with unknown or deferred diagnosis (n = 50). Electrocardiography (ECG), clinical characteristics, and ICD data were analyzed. RESULTS: J-waves were found in 27/50 patients with VF of unknown/deferred diagnosis. The J-waves were reminiscent of those seen in BS or ERS, and this subgroup of patients was termed variants of ERS and BS (VEB). In 12 VEB patients, the J/ST/T-wave morphology was coved, although amplitudes were <0.2 mV. In 15 patients, noncoved-type J/ST/T-waves were present in the right precordial leads. In the remaining 23 patients, no J-waves were identified. VEB patients exhibited clinical characteristics similar to those of BS and ERS patients. Phenotypic transition and overlap were observed among patients with BS, ERS, and VEB. Twelve patients with BS had background inferolateral ER, while five ERS patients showed prominent right precordial J-waves. Patients with this transient phenotype overlap showed a significantly lower shock-free survival than the rest of the study patients. CONCLUSIONS: VEB patients demonstrate ECG phenotype similar to but distinct from those of BS and ERS. The spectral nature of J-wave morphology/distribution and phenotypic transition/overlap suggest a common pathophysiologic background in patients with VEB, BS, and ERS. Prognostic implication of these ECG variations requires further investigation.

Extension of catheter ablation and outcome for ventricular tachycardia or premature ventricular contractions from the right ventricular outflow tract.

Objective We aimed to determine whether the extension of ablation could influence the ablation outcome for ventricular tachycardia (VT)/premature ventricular contractions (PVCs) from the right ventricular outflow tract (RVOT). Methods and results The radiofrequency catheter ablation results of 33 VT/6 frequent PVCs from the RVOT were analysed. The ablation extension was divided into 3 categories from the final successful ablation point with the earliest activation: (I) focal ablation (15 cases); ablation at 1 or 2 points; (II) focal with extended ablation (12 cases); focal and surrounding area ablation (maximum ≤1 cm) after elimination of clinical VT/PVCs; and (III) broad ablation (12 cases); continued broad ablation (maximum >1 cm) after elimination of clinical VT/PVCs. Acute termination was defined as the complete elimination and non-inducibility of clinical VT/PVCs during the procedure. For the mean follow-up of 12.8 months, the recurrence rate was not significantly different among the groups (P = 0.49). The mean procedure time was longer in group II, but ablation times and complication rates were not different among the groups. When acute termination was achieved, the overall recurrence rate was 7.6%. However, when confirming absence of the clinical VT/PVCs using 24-hour Holter monitoring immediately after the procedure, the recurrence rate was 2.7%. Conclusions Ablation extension did not affect ablation outcome of VT/PVCs from the RVOT. Confirmation of absence of clinical VT/PVCs using 24-hour Holter monitoring immediately after the procedure could guarantee long-term success.

Prevalence of Frailty and Aging-Related Health Conditions in Older Koreans in Rural Communities: a Cross-Sectional Analysis of the Aging Study of Pyeongchang Rural Area.

Frailty has been previously studied in Western countries and the urban Korean population; however, the burden of frailty and geriatric conditions in the aging populations of rural Korean communities had not yet been determined. Thus, we established a population-based prospective study of adults aged ≥ 65 years residing in rural communities of Korea between October 2014 and December 2014. All participants underwent comprehensive geriatric assessment that encompassed the assessment of cognitive and physical function, depression, nutrition, and body composition using bioimpedance analysis. We determined the prevalence of frailty based on the Cardiovascular Health Study (CHS) and Korean version of FRAIL (K-FRAIL) criteria, as well as geriatric conditions. We recruited 382 adults (98% of eligible adults; mean age: 74 years; 56% women). Generally, sociodemographic characteristics were similar to those of the general rural Korean population. Common geriatric conditions included instrumental activity of daily living disability (39%), malnutrition risk (38%), cognitive dysfunction (33%), multimorbidity (32%), and sarcopenia (28%), while dismobility (8%), incontinence (8%), and polypharmacy (3%) were less common conditions. While more individuals were classified as frail according to the K-FRAIL criteria (27%) than the CHS criteria (17%), the CHS criteria were more strongly associated with prevalent geriatric conditions. Older Koreans living in rural communities have a significant burden of frailty and geriatric conditions that increase the risk of functional decline, poor quality of life, and mortality. The current study provides a basis to guide public health professionals and policy-makers in prioritizing certain areas of care and designing effective public health interventions to promote healthy aging of this vulnerable population.

Successful Treatment with Ultrasound-Guided Aspiration of Intractable Methicillin-Resistant Staphylococcus aureus Brain Abscess in an Extremely Low Birth Weight Infant.

Brain abscesses are an uncommon and devastating complication of bacteremia in extremely low birth weight infants (<1 kg). We report a 25-week preterm neonate who developed a brain abscess 4 weeks following methicillin-resistant Staphyloccocus aureus (MRSA) sepsis. A huge brain abscess was seen with routine brain sonography on day 19 of life. Despite intravenous vancomycin treatment, the brain abscess increased in size and was associated with increased intracranial pressure on day 49 of life. The brain abscess was accompanied by mild meningeal inflammation with negative blood and cerebrospinal fluid cultures. Diagnosis of abscess was confirmed by bedside ultrasound-guided aspiration, and MRSA was isolated from the pus culture. The MRSA brain abscess refractory to vancomycin was successfully treated by surgical ultrasound-guided percutaneous needle aspiration of brain abscess and prolonged courses of antibiotic administration. At the time of this report, the infant was 9 months old (corrected age was 6 months) and had normal neurodevelopment for her corrected age on the Bayley Infant Neurodevelopmental Screener.

A case of IgG4-related disease with bronchial asthma and chronic rhinosinusitis in Korea.

IgG4-related disease (IgG4-RD) is characterized by a systemic involvement of tumor-like lesions with IgG4-positive plasmacytes. We experienced a case of IgG4-RD developed in a patient with bronchial asthma (BA) and chronic rhinosinusitis (CRS). A 55-yr-old female patient with BA and CRS complained of both eyes and neck swelling as well as a recurrent upper respiratory infection in recent 1 yr. The serum levels of IgG4, creatinine, and pancreatic enzymes were elevated. A biopsy of the submandibular gland showed an abundant infiltration of IgG4-positive plasmacytes. Her symptoms remarkably improved after the treatment of a systemic steroid that has been maintained without recurrence. We report a rare case of IgG4-RD developed in a patient with BA and CRS.

SAQ training on sprint, change-of-direction speed, and agility in U-20 female football players.

The purpose of the study was to investigate the effects of an 8-week speed, agility, and quickness (SAQ) training on performance changes in linear sprint speed, change-of-direction (COD) speed, and reactive agility of U-20 female football players. Nineteen female football players randomly served as either experimental (n = 9) or control groups (n = 10). The players were tested for physical fitness tests: linear sprint speed including both short and long distances (5- and 10-m sprints without a ball and 20- and 30-m sprints with and without dribbling), COD speed (arrowhead agility test with and without dribbling a ball, Southeast Missouri [SEMO] agility test, and 22-m repeated slalom dribbling test), and reactive agility. Significant group × time interactions were observed for sprint over long distances and COD speed but not for short sprint and reactive agility performances. Paired t-tests revealed considerable improvements in all performances from the pre-test to post-test for the SAQ group, except for the arrowhead agility (left; p = .07). The control group only exhibited significant improvements in 10-m sprint performance after general football training. Eight weeks of SAQ training were effective at enhancing acceleration, maximum sprint speed, and agility performances amongst highly trained U-20 female football players.

Performance and Physician Experience of INGEVITY+ Active Fixation Leads: Prospective INGEVITY+ Lead Clinical Study in Korea.

Background: Boston Scientific INGEVITY+ pacing lead (Boston Scientific, Marlborough, MA, USA) has been upgraded to INGEVITY. The performance of the INGEVITY+ pacing lead has not yet been reported. This study aimed to evaluate the short- and long-term safety, effectiveness, and handling experience of INGEVITY+ leads. Methods: Consecutive patients were included from 9 institutions in Korea, where 400 leads (200 right ventricular active fixation leads and 200 right atrial active fixation leads) were implanted or attempted in 200 subjects. Results: During the implantation, only one patient required a lead change because of lead screw failure. The handling questionnaires of the lead received very positive feedback with 88% of operators agreeing that it is easy for leads to pass through small vessels or vessels with multiple leads. At the 3-month follow-up, 95.7% of RA leads and 99.5% of RV leads had pacing thresholds less than 1.5 V. A total of 92.4% of atrial leads had amplitudes greater than 1.5 mV, and 96.5% of ventricular leads had sensing amplitudes greater than 5 mV at 3 months. A total of 99.8% had impedances between 300 and 1,300 ohms. The lead-related complication-free rate for all leads during follow-up was 100%, and the overall rates of lead dislodgment, perforation, and pericardial effusion were all 0.0%. Conclusions: The INGEVITY+ pacing lead exhibited exceptional clinical performance, with a high complication-free rate throughout the 3-month follow-up period. In addition, the lead displayed excellent electrical characteristics, and the lead-handling experience was reported to be very good.

Association Between Atrial Fibrillation Symptoms and Clinical Outcomes: A Prospective Multicenter Registry Study.

The presence of symptoms plays an important role in determining whether to focus on rhythm control or rate control when treating atrial fibrillation (AF). Previous comparative studies on the clinical outcomes of symptomatic and asymptomatic AF have yielded inconsistent results, and a link between AF symptoms and left atrial (LA) remodeling is not established. Patients selected from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, which is a prospective, multicenter study consisting of patients with non-valvular AF, were grouped into 2 groups: symptomatic and asymptomatic. The primary outcome was a composite of the following cardiovascular outcomes: all-cause death, ischemic stroke, transient ischemic attack, systemic embolism, myocardial infarction, and heart failure hospitalization. Of 10,210 patients with AF, 4,327 (42%) had symptomatic AF. The asymptomatic group had an older mean age, more men, and more patients with hypertension and diabetes mellitus than the symptomatic group. The asymptomatic group had a larger left atrium (LA) diameter (43.6 vs 42.2 mm, p <0.001) than the symptomatic group. During a median follow-up of 32.9 (29.5 to 36.4) months, the asymptomatic and symptomatic groups showed similar incidences of the primary outcome (1.44 vs 1.45 per 100 person-years; log-rank, p = 0.8). In conclusion, the absence of AF symptoms is associated with increased LA. However, symptomatic and asymptomatic patients with AF have a similar risk of cardiovascular outcomes. This suggests that beneficial treatment for AF may be considered regardless of whether patients have symptomatic or asymptomatic AF.

The anticoagulation one year after ablation of atrial fibrillation in patients with atrial fibrillation (ALONE-AF) trial: Study protocol.

Background: The ideal long-term antithrombotic strategy for patients after successful catheter-based atrial fibrillation (AF) ablation is still uncertain. Presently, practices vary, and the advantages of oral anticoagulation (OAC) for the post-ablation population are not clearly established. To date, no randomized trials have addressed this therapeutic question. This study aimed to evaluate whether no OAC therapy is superior to apixaban in reducing the risk of stroke, systemic embolism, or major bleeding among patients without apparent recurrent atrial arrhythmias for at least 1 year after their AF ablation procedure. Methods: The ALONE-AF trial is a prospective, multicenter, open-label, randomized study with blinded outcome assessment. Patients with AF who have at least one non-gender stroke risk factor (as determined by the CHA2DS2-VASc score) and no documented recurrences of atrial arrhythmia for at least 12 months post-ablation will be randomly assigned to apixaban 5 mg b.i.d. or no OAC therapy. The primary endpoint is a composite outcome of stroke, systemic embolism, and major bleeding. Key secondary outcomes include clinically relevant non-major bleeding, all-cause mortality, myocardial infarction, transient ischemic attack, quality of life, and frailty analysis. Participants will be followed for a period of 2 years. The estimated total sample size is 840 subjects, with 420 subjects in each arm. Conclusion: The ALONE-AF trial aims to provide robust evidence for the optimal anticoagulation strategy for patients with stroke risk factors following successful AF ablation.

Evaluation of ventricular pacing suppression algorithms in dual chamber pacemaker: Results of "LEADER" study.

Background: There is limited research on the intra-individual efficacy of ventricular pacing minimization algorithms developed by Biotronik-the Ventricular Pace Suppression algorithm (VpS) and the Intrinsic Rhythm Support plus algorithm (IRSplus) (BIOTRONIK SE & Co. KG, Berlin, Germany). We performed a randomized pilot trial that evaluated the efficacy of two algorithms in patients with symptomatic sinus node dysfunction (SND) who received a dual-chamber pacemaker. Methods: The trial was conducted in 11 tertiary hospitals in South Korea. The patients were randomized to either the VpS or IRSplus algorithm group after a 3-month period of fixed atrioventricular (AV) delay. The primary outcome was the ventricular pacing percentage (Vp%) at each follow-up visit. The secondary outcomes were the occurrence of heart failure (HF) and atrial fibrillation (AF) during the study period. Results: Data from 131 patients were analyzed. Initially, their average Vp% over 3 months with a fixed AV interval was 14.1 ± 19.4%. Patients were randomly assigned to VpS and IRSplus groups, with 66 and 65 in each. Algorithms reduced average Vp% to 4.0 ± 11.3% at 9 months and 6.7 ± 14.9% at 15 months. These algorithms were more effective for patients with paced AV delay (PAVD) ≤300 ms compared to those with PAVD >300 ms. Both algorithms were equally effective in reducing Vp%. Clinical AF or HF hospitalization was not observed during the study period. Conclusion: The VpS and IRSplus algorithms are effective and safe in minimizing unnecessary ventricular pacing in patients with SND.

Catheter ablation of left ventricular tachycardia through internal jugular vein: refining the continuous line.

A retrograde approach to the left ventricle (LV) from the femoral artery is most commonly used for left ventricular tachycardia (VT) ablation. However, as the patient population gets older, the prevalence of peripheral vascular disease and aortic valve disease increases, hampering the retrograde access to the LV, which may result in significant technical difficulties. The transseptal approach from the femoral vein is an alternative access to the LV. This approach has been effective for addressing LV VT originating from the posterior and posteroseptal region. However, the transseptal approach from the femoral vein is impossible if there are any obstacles in the inferior vena cava. There are also significant limitations in approaching the basal-lateral region of the LV from this approach. We demonstrated the safety and feasibility of catheter ablation of LV VT via the transseptal approach from the right internal jugular vein.

Apamin-sensitive calcium-activated potassium currents in rabbit ventricles with chronic myocardial infarction.

INTRODUCTION: The apamin-sensitive small-conductance calcium-activated potassium current (IKAS ) is increased in heart failure. It is unknown if myocardial infarction (MI) is also associated with an increase of IKAS . METHODS AND RESULTS: We performed Langendorff perfusion and optical mapping in 6 normal hearts and 10 hearts with chronic (5 weeks) MI. An additional 6 normal and 10 MI hearts were used for patch clamp studies. The infarct size was 25% (95% confidence interval, 20-31) and the left ventricular ejection fraction was 50 (46-54). The rabbits did not have symptoms of heart failure. The action potential duration measured to 80% repolarization (APD80 ) in the peri-infarct zone (PZ) was 150 (142-159) milliseconds, significantly (P = 0.01) shorter than that in the normal ventricles (167 [158-177] milliseconds. The intracellular Ca transient duration was also shorter in the PZ (148 [139-157] milliseconds) than that in normal ventricles (168 [157-180] milliseconds; P = 0.017). Apamin prolonged the APD80 in PZ by 9.8 (5.5-14.1)%, which is greater than that in normal ventricles (2.8 [1.3-4.3]%, P = 0.006). Significant shortening of APD80 was observed at the cessation of rapid pacing in MI but not in normal ventricles. Apamin prevented postpacing APD80 shortening. Patch clamp studies showed that IKAS was significantly higher in the PZ cells (2.51 [1.55-3.47] pA/pF, N = 17) than in the normal cells (1.08 [0.36-1.80] pA/pF, N = 15, P = 0.019). CONCLUSION: We conclude that IKAS is increased in MI ventricles and contributes significantly to ventricular repolarization especially during tachycardia.

Effects of Exhaustive Exercise on Inflammatory, Apoptotic, and Antioxidative Signaling Pathways in Human Peripheral Blood Mononuclear Cells.

In the present study, we investigated the effects of exhaustive exercise and recovery on inflammatory, pro-apoptotic, and anti-oxidative responses in human peripheral blood mononuclear cells (PBMCs). Sixteen volunteers participated in a guided physical activity program in which they were subjected to progressive exercise on the treadmill until they were exhausted followed by an 1-hour recovery period. Isolated human PBMCs were collected before exercise, immediately after exercise, and after 1-hour recovery. Exhaustive exercise induced expression of heme oxygenase-1 and glutamate cysteine ligase catalytic subunit and activation of NF-κB and NF-E2 related factor 2 (Nrf2). Apoptosis, as measured by activity and cleavage of caspase-3 and its substrate PARP also significantly increased. However, induction of redox signaling and the pro-apoptotic response fully returned to the baseline level during the 1-hour recovery period. On the other hand, COX-2 expression was continuously elevated after exercise cessation throughout the 1-hour recovery period. Taking all these findings into account, we conclude that exhaustive exercise transiently induces Nrf2-mediated antioxidant gene expression and eliminates damaged cells through apoptosis as part of an adaptive cytoprotective response against oxidative and inflammatory stress.

Comparing the Efficacy of Carvedilol and Flecainide on the Treatment of Idiopathic Premature Ventricular Complexes from Ventricular Outflow Tract: A Multicenter, Randomized, Open-Label Pilot Study.

The mechanism of premature ventricular complexes (PVC) occurring in the ventricular outflow tract (OT) is related to an intracellular calcium overload and delayed afterdepolarizations that lead to triggered activity. The guidelines recommend using beta-blockers and flecainide for idiopathic PVCs, but they also acknowledge the limited evidence supporting this recommendation. We conducted a multicenter, randomized, open-label pilot study comparing the effect of carvedilol and flecainide on OT PVC, which are widely used to treat this arrhythmia. Patients with a 24 h Holter recording a PVC burden ≥ 5%, which showed positive R waves in leads II, III, and aVF, and without structural heart disease were enrolled. They were randomly assigned to the carvedilol or flecainide group, and the maximum tolerated dose was administered for 12 weeks. A total of 103 participants completed the protocol: 51 with carvedilol and 52 with flecainide. After 12 weeks of treatment, the mean PVC burden significantly decreased in both groups: 20.3 ± 11.5 to 14.6 ± 10.8% with carvedilol (p < 0.0001) and 17.1 ± 9.9 to 6.6 ± 9.9% with flecainide (p < 0.0001). Both carvedilol and flecainide effectively suppressed OT PVCs in patients without structural heart disease, with flecainide showing a superior efficacy compared to carvedilol.