Continuous monitoring of an arterial pulse using a pressure sensor attached on the epidermis is an important technology for detecting the early onset of cardiovascular disease and assessing personal ...health status. Conventional pulse sensors have the capability of detecting human biosignals, but have significant drawbacks of power consumption issues that limit sustainable operation of wearable medical devices. Here, a self‐powered piezoelectric pulse sensor is demonstrated to enable in vivo measurement of radial/carotid pulse signals in near‐surface arteries. The inorganic piezoelectric sensor on an ultrathin plastic achieves conformal contact with the complex texture of the rugged skin, which allows to respond to the tiny pulse changes arising on the surface of epidermis. Experimental studies provide characteristics of the sensor with a sensitivity (≈0.018 kPa−1), response time (≈60 ms), and good mechanical stability. Wireless transmission of detected arterial pressure signals to a smart phone demonstrates the possibility of self‐powered and real‐time pulse monitoring system.
A self‐powered, flexible, and piezoelectric pressure sensor for real‐time arterial pulse monitoring is demonstrated on ultrathin substrates via an inorganic‐based laser lift‐off process. The ultrathin self‐powered sensor with good sensitivity of 0.018 kPa−1 adheres to human epidermis and successfully detects arterial pulse and respiration. Finally, pulse signals are wirelessly transmitted to a smart phone for realizing wearable healthcare sensors.
Curcumin exerts therapeutic effects in heart disease, but has limited bioavailability. Extracellular vesicles (EVs) have gained attention as nanovehicles; however, the poor targeting ability of ...systemically administered EVs still remains a crucial issue. Herein, we generated heart-targeted EVs (CTP-EVs) by functionalizing EVs surface with cardiac targeting peptide (CTP) using genetic modification of EVs-secreting cells, and further loaded curcumin into CTP-EVs (CTP-EVs-Cur). Consequently, CTP-EVs were able to specifically deliver curcumin to the heart. In addition, curcumin-loaded CTP-EVs possess improved bioavailability, and are fully functional with a high cardioprotective efficiency. Moreover, we loaded miR-144-3p in CTP-EVs-Cur following validation of miR-144-3p as a major contributor in curcumin-mediated therapeutic effects. The simultaneous packing of curcumin and miR-144-3p in CTP-EVs not only retains the active heart-targeting ability but also achieves enhanced cardioprotective effects both in vitro and in vivo, indicating the possibility of combining and sustaining their therapeutic potential by simultaneously loading in CTP-EVs. Therefore, CTP-EVs could be a potential and effective strategy for the delivery of therapeutic molecules, thereby providing a promising nanomedicine for MI therapy.
Schematic illustration of heart-targeted co-delivery of curcumin and miRNA-144-3p using surface functionalized EVs (CTP-EVs) for myocardial infarction therapy. Display omitted
•The miR-144-3p functions as a major contributor in curcumin-mediated cardioprotective effects.•Curcumin-loaded CTP-EVs provide a superior ability to promote heart-targeted therapy.•Co-delivery of curcumin and miR-144-3p using CTP-EVs achieves enhanced therapeutic effects on MI.
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.
Naturally occurring RNA carriers such as exosomes might be an untapped source of effective delivery vehicles. However, if exosomes are to be exploited for therapeutic applications, they must target ...specific tissues or cell types to avoid off-target effects. This study evaluated whether genetic modification of exosomes could enhance exosome delivery to heart cells and heart tissue without toxicity. Exosomes expressing cardiac-targeting peptide (CTP)-Lamp2b on the exosomal membrane (CTP-Exo) were generated by introducing vectors encoding CTP-Lamp2b into HEK 293 cells. The expression of CTP-Lamp2b peptide on exosomes was stabilized by attaching glycosylation sequences. Exosomes expressing only Lamp2b on exosomal membranes (CTL-Exo) were generated as a control. The in vitro and in vivo uptake of CTL-Exo and CTP-Exo was evaluated in cell lines and mice. Both exosomes were delivered to HEK 293 and H9C2 cells. The delivery of the exosome was not different between CTP-Exo and CTL-Exo in HEK 293 cells, whereas the delivery of CTP-Exo was 16% greater than that of CTL-Exo in H9C2 cells (P = 0.047). Cell viability was maintained at almost 100% with different dosages of both CTL-Exo and CTP-Exo. Moreover, compared with CTL-Exo, the in vivo delivery of exosomes to the hearts of mice was increased by 15% with CTP-Exo (P = 0.035). The delivery to livers and spleens was not different between the two exosomes. Genetic modification of exosomes by expressing CTP-Lamp2b on the exosomal membrane enhanced exosome delivery to heart cells and the heart tissue. These results suggested that CTP-Exo might be used as a therapeutic tool for heart disease.
•Genetic modification of exosomes could enhance exosome delivery to heart.•CTP-Exo did not show toxic effects in vitro or in vivo.•CTP-Exo might be used as a therapeutic tool for heart disease.
Additional surgeries for implantable biomedical devices are inevitable to replace discharged batteries, but repeated surgeries can be a risk to patients, causing bleeding, inflammation, and ...infection. Therefore, developing self‐powered implantable devices is essential to reduce the patient's physical/psychological pain and financial burden. Although wireless communication plays a critical role in implantable biomedical devices that contain the function of data transmitting, it has never been integrated with in vivo piezoelectric self‐powered system due to its high‐level power consumption (microwatt‐scale). Here, wireless communication, which is essential for a ubiquitous healthcare system, is successfully driven with in vivo energy harvesting enabled by high‐performance single‐crystalline (1 − x)Pb(Mg1/3Nb2/3)O3−(x)Pb(Zr,Ti)O3 (PMN‐PZT). The PMN‐PZT energy harvester generates an open‐circuit voltage of 17.8 V and a short‐circuit current of 1.74 µA from porcine heartbeats, which are greater by a factor of 4.45 and 17.5 than those of previously reported in vivo piezoelectric energy harvesting. The energy harvester exhibits excellent biocompatibility, which implies the possibility for applying the device to biomedical applications.
In vivo self‐powered wireless transmission using a flexible single‐crystalline piezoelectric energy harvester is demonstrated. The high‐performance energy harvester generates an output voltage of 17.8 V and a current of 1.75 µA from the contraction and relaxation motion of porcine heart. The energy from in vivo physiological motion enables self‐powered wireless transmission, thus realizing practical application in the ubiquitous healthcare system.
Abstract
Aims
Accumulating evidence shows that atrial fibrillation (AF) is associated with an increased risk of dementia. Catheter ablation for AF prolongs the duration of sinus rhythm, thereby ...improving the quality of life. We investigated the association of catheter ablation for AF with the occurrence of dementia.
Methods and results
Using the Korean National Health Insurance Service database, among 194 928 adults with AF treated with ablation or medical therapy (antiarrhythmic or rate control drugs) between 1 January 2005 and 31 December 2015, we studied 9119 patients undergoing ablation and 17 978 patients managed with medical therapy. The time-at-risk was counted from the first medical therapy, and ablation was analysed as a time-varying exposure. Propensity score-matching was used to correct for differences between the groups. During a median follow-up of 52 months, compared with patients with medical therapy, ablated patients showed lower incidence and risk of overall dementia (8.1 and 5.6 per 1000 person-years, respectively; hazard ratio 0.73, 95% confidence interval 0.58–0.93). The associations between ablation and dementia risk were consistently observed after additionally censoring for incident stroke (hazard ratio 0.76, 95% confidence interval 0.61–0.95) and more pronounced in cases of ablation success whereas no significant differences observed in cases of ablation failure. Ablation was associated with lower risks of dementia subtypes including Alzheimer’s disease and vascular dementia.
Conclusion
In this nationwide cohort of AF patients treated with catheter ablation or medical therapy, ablation was associated with decreased dementia risk. This relationship was evident after censoring for stroke and adjusting for clinical confounders.
Graphical Abstract
Background: Catheter ablation is a good treatment option for atrial fibrillation (AF) in young symptomatic patients. However, there is little information on the efficacy of catheter ablation of ...early-onset AF between sexes. Methods and Results: This study included 1,060 patients under the age 60 years old (837 men, 49.8±7.7 years old, 70.8% paroxysmal AF) who underwent catheter ablation for AF. Sex differences in clinical presentation and ablation outcomes were compared with and without propensity score-matching. During 24.5±18.9 months of follow-up, women showed significantly higher clinical recurrence of AF than men (log-rank, P=0.002). Female sex was independently associated with post-ablation clinical recurrence of AF (adjusted hazard ratio (HR) 2.58 1.06–6.30, P=0.037). Women had a higher proportion of left ventricular diastolic dysfunction (E/Em, P<0.001), higher prevalence of heart failure (P=0.017), greater left atrial (LA) volume index (P=0.001), lower LA endocardial voltage (P<0.001), and higher parasympathetic nervous activity (root-mean square of differences, P<0.001; high-frequency (HF), P=0.010) than men. After a second ablation procedure (n=111), women still showed a higher clinical recurrence rate than men (log-rank, P=0.003) during 22.9±15.0 months of follow-up. Conclusions: Among patients with early-onset AF who underwent catheter ablation, women showed poorer clinical outcomes than men after de novo and second procedures. Left ventricular dysfunction, LA remodeling, and autonomic nervous function may be potential mechanisms underlying sex differences in catheter ablation outcomes of early-onset AF.
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(In sub(1/2)Nb sub(1/2))O sub(3)-Pb(Mg sub(1/3)Nb sub(2/3))O sub(3)-PbTiO sub(3 ) (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.
For healthy populations without comorbidities, whether prehypertension and impaired fasting glucose (IFG) are associated with new onset atrial fibrillation (AF) is not well known.
We included 366 507 ...subjects (age ≥20 years) not diagnosed with non-valvular AF from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) from 2003 to 2008. In total, 139 306 subjects diagnosed with AF-related comorbidities were excluded, and a 227 102 healthy population was followed up until 2013. The body mass index (BMI), blood pressure (BP), and fasting blood glucose (BG) level were acquired during National health check-ups. Subjects with IFG hazard ratio (HR) 1.16, P = 0.017 had a higher AF risk and the diastolic BP (HR 1.11, P = 0.045) was a stronger indicator for an AF incidence than the systolic BP. After dividing the subjects into two mutually exclusive groups, AF incidence was increased dramatically by the combination effect of both prehypertension and an IFG in BMI <25 kg/m2 group, but, in BMI ≧25 kg/m2 group, did not show this tendency. An IFG related to AF risk was more prominent in the BMI <25 kg/m2 population (HR 1.18, P = 0.025) than those with a BMI ≥25 kg/m2, and subjects with both an IFG and prehypertension had a greater AF risk (HR 1.27, P = 0.016) than those without.
Even in a healthy Asian populations without comorbidities, prehypertension and IFG were important risk factors of AF. Specifically, when prehypertension, including systolic and diastolic BPs, was finally combined with the IFG, the risk of new onset AF was increased especially in the BMI <25 kg/m2 group.
Temporal changes in the healthcare burden of atrial fibrillation (AF) are less well known in rapidly ageing Asian countries. We examined trends in hospitalisations, costs, treatment patterns and ...outcomes related to AF in Korea.
Using the National Health Insurance Service (NHIS) database involving the entire adult Korean population (n=41 701 269 in 2015), we analysed a nationwide AF cohort representing 931 138 patients with AF. We studied all hospitalisations due to AF from 2006 to 2015.
Overall, hospitalisations for AF increased by 420% from 767 to 3986 per 1 million Korean population from 2006 to 2015. Most admissions occurred in patients aged ≥70 years, and the most frequent coexisting conditions were hypertension, heart failure and chronic obstructive pulmonary disease. Hospitalisations mainly due to major bleeding and AF control increased, whereas hospitalisations mainly due to ischaemic stroke and myocardial infarction decreased. The total cost of care increased even after adjustment for inflation from €68.4 million in 2006 to €388.4 million in 2015, equivalent to 0.78% of the Korean NHIS total expenditure. Overall in-hospital mortality decreased from 7.5% in 2006 to 4.3% in 2015. The in-hospital mortality was highest in patients ≥80 years of age (7.7%) and in patients with chronic kidney disease (7.4%).
AF hospitalisations have increased exponentially over the past 10 years in Korea, in association with an increase in comorbid chronic diseases. Mortality associated with AF hospitalisations decreased during the last decade, but hospitalisation costs have markedly increased.
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