Boyoung Joung

Self-Powered Cardiac Pacemaker Enabled by Flexible Single Crystalline PMN-PT Piezoelectric Energy Harvester

A flexible single-crystalline PMN-PT piezoelectric energy harvester is demonstrated to achieve a self-powered artificial cardiac pacemaker. The energy-harvesting device generates a short-circuit current of 0.223 mA and an open-circuit voltage of 8.2 V, which are enough not only to meet the standard for charging commercial batteries but also for stimulating the heart without an external power source.

Self-powered deep brain stimulation via a flexible PIMNT energy harvester

Deep brain stimulation (DBS) is widely used for neural prosthetics and brain–computer interfacing. Thus far in vivo implantation of a battery has been a prerequisite to supply the necessary power. Although flexible energy harvesters have recently emerged as alternatives to batteries, they generate insufficient energy for operating brain stimulation. Herein, we report a high performance flexible piezoelectric energy harvester by enabling self-powered DBS in mice. This device adopts an indium modified crystalline Pb(In1/2Nb1/2)O3–Pb(Mg1/3Nb2/3)O3–PbTiO3 (PIMNT) thin film on a plastic substrate to transform tiny mechanical motions to electricity. With slight bending, it generates an extremely high current reaching 0.57 mA, which satisfies the high threshold current for real-time DBS of the motor cortex and thereby could efficiently induce forearm movements in mice. The PIMNT based flexible energy harvester could open a new avenue for future in vivo healthcare technology using self-powered biomedical devices.

First-degree atrioventricular block is associated with advanced atrioventricular block, atrial fibrillation and left ventricular dysfunction in patients with hypertension.

OBJECTIVES: Clinical significance of first-degree atrioventricular block (AVB) have not been known in patients with hypertension. This study was performed to elucidate long-term prognosis of first-degree AVB in patients with hypertension. METHODS: We included 3816 patients (mean age, 61.0 ± 10.6 years; men, 47.2%) with hypertension. We reviewed their ECGs and measured the PR interval. The patients were divided into two groups: normal PR interval (120 ms ≤ PR ≤200 ms) and first-degree AVB (PR >200 ms). We compared the incidence, cumulative incidence and hazard ratios of advanced AVB, sick sinus syndrome, atrial fibrillation and left ventricular dysfunction between the two groups during the follow-up period. RESULTS: The prevalence of first-degree AVB in patients with hypertension was 14.3%. The patients were followed up for 9.4 ± 2.4 years. Incidence and cumulative incidence of advanced AVB, atrial fibrillation and left ventricular dysfunction in patients with first-degree AVB were significantly higher than in patients with normal PR interval. By multivariate Coxs regression, patients with first-degree AVB had an increased risk of advanced AVB [hazard ratio 2.77; 95% confidence interval (95% CI) 1.38-5.59; P = 0.004], atrial fibrillation (hazard ratio 2.33; 95% CI 1.84-2.94; P < 0.001) and left ventricular dysfunction (hazard ratio 1.49; 95% CI 1.11-2.00; P = 0.009). However, sick sinus syndrome was not associated with first-degree AVB. CONCLUSION: First-degree AVB is an independent risk factor for future development of advanced AVB, atrial fibrillation and left ventricular dysfunction in patients with hypertension.Background: Chronic kidney disease (CKD) is characterized by aortic stiffness and increased cardiovascular mortality. In end-stage renal disease, aortic stiffness predicts mortality, whereas this role remains uncertain in mild-to-moderate CKD. We aimed to investigate whether aortic pulse wave velocity (aPWV) predicts mortality and renal disease progression in CKD patients. Methods: We enrolled 135 CKD patients stages 2–4 [estimated glomerular filtration rate (eGFR): 41.1 (28.5–61.6) ml/min per 1.73 m2] in the study and assessed aPWV. The combined renal end-point was defined as at least 50% decline in renal function and/or start of renal replacement therapy. Results: During the observational period of 42 (30–50) months six patients were lost of follow-up, 13 patients died and 16 patients reached the combined renal end-point. Stratification according to the mean of aPWV (10 m/s), Kaplan–Meier analysis revealed increased mortality with aPWV ≥10 m/s (log-rank P < 0.05). Stepwise logistic regression analysis confirmed aPWV as an independent predictor for mortality in CKD stage 2–4. The hazard ratio of mortality in the cohort with an aPWV at least 10 m/s was 5.1 (1.1–22.9). By contrast, Kaplan–Meier analysis revealed no effect of aPWV on the combined renal end-point (log-rank P = 0.90). Discussion: These results provide the first direct evidence that in patients with CKD stage 2–4, increased aortic stiffness determined by aPWV is a strong independent predictor of all-cause mortality.OBJECTIVES Clinical significance of first-degree atrioventricular block (AVB) have not been known in patients with hypertension. This study was performed to elucidate long-term prognosis of first-degree AVB in patients with hypertension. METHODS We included 3816 patients (mean age, 61.0 ± 10.6 years; men, 47.2%) with hypertension. We reviewed their ECGs and measured the PR interval. The patients were divided into two groups: normal PR interval (120 ms ≤ PR ≤200 ms) and first-degree AVB (PR >200 ms). We compared the incidence, cumulative incidence and hazard ratios of advanced AVB, sick sinus syndrome, atrial fibrillation and left ventricular dysfunction between the two groups during the follow-up period. RESULTS The prevalence of first-degree AVB in patients with hypertension was 14.3%. The patients were followed up for 9.4 ± 2.4 years. Incidence and cumulative incidence of advanced AVB, atrial fibrillation and left ventricular dysfunction in patients with first-degree AVB were significantly higher than in patients with normal PR interval. By multivariate Coxs regression, patients with first-degree AVB had an increased risk of advanced AVB [hazard ratio 2.77; 95% confidence interval (95% CI) 1.38-5.59; P = 0.004], atrial fibrillation (hazard ratio 2.33; 95% CI 1.84-2.94; P < 0.001) and left ventricular dysfunction (hazard ratio 1.49; 95% CI 1.11-2.00; P = 0.009). However, sick sinus syndrome was not associated with first-degree AVB. CONCLUSION First-degree AVB is an independent risk factor for future development of advanced AVB, atrial fibrillation and left ventricular dysfunction in patients with hypertension.

The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

The current manuscript is the second update of the original Practical Guide, published in 2013 [Heidbuchel et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are as follows i.e., (1) Eligibility for NOACs; (2) Practical start-up and follow-up scheme for patients on NOACs; (3) Ensuring adherence to prescribed oral anticoagulant intake; (4) Switching between anticoagulant regimens; (5) Pharmacokinetics and drug-drug interactions of NOACs; (6) NOACs in patients with chronic kidney or advanced liver disease; (7) How to measure the anticoagulant effect of NOACs; (8) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (9) How to deal with dosing errors; (10) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (11) Management of bleeding under NOAC therapy; (12) Patients undergoing a planned invasive procedure, surgery or ablation; (13) Patients requiring an urgent surgical intervention; (14) Patients with AF and coronary artery disease; (15) Avoiding confusion with NOAC dosing across indications; (16) Cardioversion in a NOAC-treated patient; (17) AF patients presenting with acute stroke while on NOACs; (18) NOACs in special situations; (19) Anticoagulation in AF patients with a malignancy; and (20) Optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA website (www.NOACforAF.eu).

Antiarrhythmic Potential of Mesenchymal Stem Cell Is Modulated by Hypoxic Environment

OBJECTIVES The purpose of this study was to evaluate the antiarrhythmic potential of mesenchymal stem cells (MSC) under a different environment. BACKGROUND Little is known about how environmental status affects antiarrhythmic potential of MSCs. METHODS To investigate the effect of paracrine factors secreted from MSCs under different circumstances on arrhythmogenicity in rats with myocardial infarction, we injected paracrine media (PM) secreted under hypoxic, normoxic conditions (hypoxic PM and normoxic PM), and MSC into the border zone of infarcted myocardium in rats. RESULTS We found that the injection of hypoxic PM, but not normoxic PM, markedly restored conduction velocities, suppressed focal activity, and prevented sudden arrhythmic deaths in rats. Underlying this electrophysiological alteration was a decrease in fibrosis, restoration of connexin 43, alleviation of Ca(2+) overload, and recovery of Ca(2+)-regulatory ion channels and proteins, all of which is supported by proteomic data showing that several paracrine factors including basic fibroblast growth factor, insulinlike growth factor 1, hepatocyte growth factor, and EF-hand domain-containing 2 are potential mediators. When compared with PM, MSC injection did not reduce or prevent arrhythmogenicity, suggesting that the antiarrhythmic or proarrhythmic potential of MSC is mainly dependent on paracrine factors. CONCLUSIONS A hypoxic or normoxic environment surrounding MSC affects the type and properties of the growth factors or cytokines, and these secreted molecules determine the characteristics of the electro-anatomical substrate of the surrounding myocardium.

Does additional linear ablation after circumferential pulmonary vein isolation improve clinical outcome in patients with paroxysmal atrial fibrillation? Prospective randomised study

Objective Circumferential pulmonary vein isolation (CPVI) has been considered the cornerstone of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). However, it is unclear whether linear ablation in addition to CPVI improves clinical outcome. Design Prospective randomised study to compare the efficacy of CPVI and CPVI with additional linear ablation in patients with paroxysmal AF (PAF). Setting University hospital. Patients This study enrolled 156 patients (male 76.3%, 55.8±11.5 years old (mean±SD)) who underwent RFCA for PAF. Interventions CPVI (n=52), CPVI+roof line (CPVI+RL; n=52) and CPVI+RL+posterior inferior line (CPVI+PostBox; n=52). Main outcome measures Procedure time, ablation time and clinical outcome. Results (1) The CPVI group showed shorter total procedure time (180.4±39.5 min vs 189.6±29.0 min and 201.7±51.7 min, respectively (mean±SD); p=0.035) and ablation time (4085.5±1384.1 s vs 5253.5±1010.9 s and 5495.0±1316.0 s, respectively; p<0.001) than the CPVI+RL and CPVI+PostBox groups. (2) During 15.6±5.0 months of follow-up, the recurrence rates 3 months after RFCA were 11.5% in CPVI, 21.2% in CPVI+RL and 19.2% in CPVI+PostBox (p=0.440). (3) The achievement rate of CPVI was 100.0%, and bidirectional block rate was 80.8% in CPVI+RL and 59.6% in CPVI+PostBox. The clinical recurrence rates with or without achieving bidirectional block were not significantly different from each other (p=0.386). Conclusion In patients with PAF, linear ablation in addition to CPVI did not improve clinical outcome, regardless of bidirectional block achievement, while it prolonged the total procedure and ablation time.

Impact of increased orifice size and decreased flow velocity of left atrial appendage on stroke in nonvalvular atrial fibrillation.

The structural and functional characteristics of left atrial appendage (LAA) in patients with atrial fibrillation (AF) with previous stroke remain incompletely elucidated. This study investigated whether a larger LAA orifice is related to decreased LAA flow velocity and stroke in nonvalvular AF. The dimension, morphology, and flow velocity of LAA were compared in patients with nonvalvular AF with (stroke group, n = 67, mean age 66 ± 9 years) and without ischemic stroke (no-stroke group, n = 151, mean age 56 ± 10 years). Compared with no-stroke group, the stroke group had larger LA dimension (4.7 ± 0.8 vs 4.2 ± 0.6 cm, p <0.001), larger LAA orifice area (4.5 ± 1.5 vs 3.0 ± 1.1 cm(2), p <0.001), and slower LAA flow velocity (36 ± 19 vs 55 ± 20 cm/s, p <0.001). LAA flow velocity was negatively correlated with LAA orifice size (R = -0.48, p <0.001). After adjustment for multiple potential confounding factors including CHA2DS2-VASc score, persistent AF, and LA dimension, large LAA orifice area (odds ratio 6.16, 95% confidence interval 2.67 to 14.18, p <0.001) and slow LAA velocity (odds ratio 3.59, 95% confidence interval 1.42 to 9.08, p = 0.007) were found to be significant risk factors of stroke. In patients with LAA flow velocity <37.0 cm/s, patients with large LAA orifice (>3.5 cm(2)) had greater incidence of stroke than those with LAA orifice of ≤3.5 cm(2) (75% vs 23%, p <0.001). In conclusion, LAA orifice enlargement was related to stroke risk in patients with nonvalvular AF even after adjustment for other risk factors, and it could be the cause of decreased flow velocity in LAA.

The electroanatomical remodelling of the left atrium is related to CHADS2/CHA2DS2VASc score and events of stroke in patients with atrial fibrillation

BACKGROUND Although atrial fibrillation (AF) increases the risk of stroke, its relationship with atrial remodelling has not yet been studied. We hypothesized that the degree of electroanatomical remodelling of the left atrium (LA) is related to CHADS₂/CHA₂DS₂VASc score and events of stroke. METHODS AND RESULTS We compared CHADS₂/CHA₂DS₂VASc score (0, 1, ≥ 2) or events of stroke with mean and regional LA volume [by three-dimensional (3D) computed tomography images] or LA endocardial voltage (by 3D-electroanatomical map) in 348 patients who underwent catheter ablation of AF (78.4% male, 55.4 ± 11.0 years old, paroxysmal AF:persistent AF = 215:133). We graded LA volume index as Grade 1 (< 48.3 mL/m²; n= 80), grade 2 (48.3-63.0 mL/m², n= 82), grade 3 (63.0-99.0 mL/m²; n= 94), and grade 4 (≥ 99.0 mL/m²; n= 92). Results (i) The percentage volume of anterior portion of LA enlarged at the early stage of LA remodelling (Grade 1 vs. grade 2, P= 0.006) and the voltage of posterior venous LA was significantly reduced with the degree of LA remodelling (P= 0.001). (ii) Mean LA volume/body surface area (BSA), especially anterior portion of LA, was greater in patients with high CHADS₂/CHA₂DS₂VASc score (P= 0.002). Mean LA voltage was significantly lower in patients with high CHA₂DS₂VASc score than low score (P= 0.007). (iii) In patients who experience stroke (n= 22), LA volume/BSA, especially anterior LA, was greater (P= 0.012), and LA endocardial voltage was lower (P= 0.039) than those without stroke. CONCLUSION Electroanatomical remodelling of LA, estimated by LA volume and endocardial voltage, has significant relationship with the risk scores or events of stroke in patients with non-valvular AF.

Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation

Ambient particulate matter (PM) can increase the incidence of arrhythmia. However, the arrhythmogenic mechanism of PM is poorly understood. This study investigated the arrhythmogenic mechanism of PM. In Sprague-Dawley rats, QT interval was increased from 115.0±14.0 to 142.1±18.4ms (p=0.02) after endotracheal exposure of DEP (200μg/ml for 30min, n=5). Ventricular premature contractions were more frequently observed after DEP exposure (100%) than baseline (20%, p=0.04). These effects were prevented by pretreatment of N-acetylcysteine (NAC, 5mmol/L, n=3). In 12 Langendorff-perfused rat hearts, DEP infusion of 12.5μg/ml for 20min prolonged action potential duration (APD) at only left ventricular base increasing apicobasal repolarization gradients. Spontaneous early afterdepolarization (EAD) and ventricular tachycardia (VT) were observed in 8 (67%) and 6 (50%) hearts, respectively, versus no spontaneous triggered activity or VT in any hearts before DEP infusion. DEP-induced APD prolongation, EAD and VT were successfully prevented with NAC (5mmol/L, n=5), nifedipine (10μmol/L, n=5), and active Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1μmol/L, n=5), but not by thapsigargin (200nmol/L) plus ryanodine (10μmol/L, n=5) and inactive CaMKII blockade, KN 92 (1μmol/L, n=5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5μg/ml) induced apoptosis, and this effect was prevented by NAC and KN 93. Thus, this study shows that in vivo and vitro exposure of PM induced APD prolongation, EAD and ventricular arrhythmia. These effects might be caused by oxidative stress and CaMKII activation.

High left atrial pressures are associated with advanced electroanatomical remodeling of left atrium and independent predictors for clinical recurrence of atrial fibrillation after catheter ablation

BACKGROUND The clinical significance of left atrial pressure (LAP) has not yet been clearly elucidated in patients with atrial fibrillation (AF). OBJECTIVE To explore the effects of elevated LAP on pathophysiology and clinical outcome after radiofrequency catheter ablation in patients with AF. METHODS We measured LAP during both sinus rhythm (SR) and AF in 454 patients 348 (76.7%) men; mean age 58 ± 11 years; 326(71.8%) paroxysmal AF) who underwent radiofrequency catheter ablation and compared LAP at v wave (LAPpeak) and LAP at y descent (LAPnadir) by using imaging (echocardiography and computed tomography), electrophysiologic mapping (NavX), and clinical data. In 280 (61.7%) patients, pulmonary vein (PV) diastolic flow velocity was measured during SR by transesophageal echocardiography. RESULTS Patients with LAPpeak(SR) ≥19 mm Hg had greater left atrial (LA) dimension (P < .001), LA volume index (P = .003), and E/Em (mitral annular septal area [peak diastolic velocity]; P = .001) but reduced LA voltage (P < .001) and mitral annular septal area (peak systolic velocity; P = .006) compared with patients with LAPpeak(SR) <19 mm Hg. High LAPpeak(SR) was independently associated with anterior LA volume (linear regression coefficient [B] = 0.381; 95% confidence interval [CI] 0.169-0.593; P < .001) and low LA voltage (B = -0.022; 95% CI -0.030 to -0.013; P < .001). PV diastolic flow velocity (B = 0.161; 95% CI 0.083-0.239; P < .001) and E/Em (B = 0.430; 95% CI 0.096-0.763; P = .012) were independent, noninvasive parameters associated with high LApeak(SR). During 13.1 ± 6.0 months of follow-up, high LAPpeak(SR) was an independent predictor for clinical recurrence of AF (hazard ratio 1.887; 95% CI 1.063-3.350; P = .028). CONCLUSION Elevated LAP was closely associated with electroanatomical remodeling of the LA and was an independent predictor for recurrence after AF ablation. PV diastolic flow velocity and E/Em can be used as a noninvasive parameter predicting high LAPpeak(SR) in patients with AF.