SciCombinator

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Concept: Cardiac electrophysiology

445

Flexible, wearable sensing devices can yield important information about the underlying physiology of a human subject for applications in real-time health and fitness monitoring. Despite significant progress in the fabrication of flexible biosensors that naturally comply with the epidermis, most designs measure only a small number of physical or electrophysiological parameters, and neglect the rich chemical information available from biomarkers. Here, we introduce a skin-worn wearable hybrid sensing system that offers simultaneous real-time monitoring of a biochemical (lactate) and an electrophysiological signal (electrocardiogram), for more comprehensive fitness monitoring than from physical or electrophysiological sensors alone. The two sensing modalities, comprising a three-electrode amperometric lactate biosensor and a bipolar electrocardiogram sensor, are co-fabricated on a flexible substrate and mounted on the skin. Human experiments reveal that physiochemistry and electrophysiology can be measured simultaneously with negligible cross-talk, enabling a new class of hybrid sensing devices.

Concepts: Chemistry, Electrophysiology, Cardiac electrophysiology, Signal processing, Electroencephalography, Skin, Sensors, Electrocardiography

388

Background The presence of a cardiovascular implantable electronic device has long been a contraindication for the performance of magnetic resonance imaging (MRI). We established a prospective registry to determine the risks associated with MRI at a magnetic field strength of 1.5 tesla for patients who had a pacemaker or implantable cardioverter-defibrillator (ICD) that was “non-MRI-conditional” (i.e., not approved by the Food and Drug Administration for MRI scanning). Methods Patients in the registry were referred for clinically indicated nonthoracic MRI at a field strength of 1.5 tesla. Devices were interrogated before and after MRI with the use of a standardized protocol and were appropriately reprogrammed before the scanning. The primary end points were death, generator or lead failure, induced arrhythmia, loss of capture, or electrical reset during the scanning. The secondary end points were changes in device settings. Results MRI was performed in 1000 cases in which patients had a pacemaker and in 500 cases in which patients had an ICD. No deaths, lead failures, losses of capture, or ventricular arrhythmias occurred during MRI. One ICD generator could not be interrogated after MRI and required immediate replacement; the device had not been appropriately programmed per protocol before the MRI. We observed six cases of self-terminating atrial fibrillation or flutter and six cases of partial electrical reset. Changes in lead impedance, pacing threshold, battery voltage, and P-wave and R-wave amplitude exceeded prespecified thresholds in a small number of cases. Repeat MRI was not associated with an increase in adverse events. Conclusions In this study, device or lead failure did not occur in any patient with a non-MRI-conditional pacemaker or ICD who underwent clinically indicated nonthoracic MRI at 1.5 tesla, was appropriately screened, and had the device reprogrammed in accordance with the prespecified protocol. (Funded by St. Jude Medical and others; MagnaSafe ClinicalTrials.gov number, NCT00907361 .).

Concepts: Electromagnetism, Magnetic field, X-ray, Spin, Implantable cardioverter-defibrillator, Cardiac electrophysiology, Magnetic resonance imaging, Artificial pacemaker

247

Premature cardiac contractions are associated with increased morbidity and mortality. Though experts associate premature atrial contractions (PACs) and premature ventricular contractions (PVCs) with caffeine, there are no data to support this relationship in the general population. As certain caffeinated products may have cardiovascular benefits, recommendations against them may be detrimental.

Concepts: Cardiac electrophysiology, Premature ventricular contraction, Premature atrial contraction

201

Sudden cardiac death exhibits diurnal variation in both acquired and hereditary forms of heart disease, but the molecular basis of this variation is unknown. A common mechanism that underlies susceptibility to ventricular arrhythmias is abnormalities in the duration (for example, short or long QT syndromes and heart failure) or pattern (for example, Brugada’s syndrome) of myocardial repolarization. Here we provide molecular evidence that links circadian rhythms to vulnerability in ventricular arrhythmias in mice. Specifically, we show that cardiac ion-channel expression and QT-interval duration (an index of myocardial repolarization) exhibit endogenous circadian rhythmicity under the control of a clock-dependent oscillator, krüppel-like factor 15 (Klf15). Klf15 transcriptionally controls rhythmic expression of Kv channel-interacting protein 2 (KChIP2), a critical subunit required for generating the transient outward potassium current. Deficiency or excess of Klf15 causes loss of rhythmic QT variation, abnormal repolarization and enhanced susceptibility to ventricular arrhythmias. These findings identify circadian transcription of ion channels as a mechanism for cardiac arrhythmogenesis.

Concepts: Cardiology, Heart, Sleep, Cardiac arrest, Cardiac electrophysiology, Long QT syndrome, Circadian rhythm, Sudden cardiac death

197

Transplantation studies in mice and rats have shown that human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted hearts, but two critical issues related to their electrophysiological behaviour in vivo remain unresolved. First, the risk of arrhythmias following hESC-CM transplantation in injured hearts has not been determined. Second, the electromechanical integration of hESC-CMs in injured hearts has not been demonstrated, so it is unclear whether these cells improve contractile function directly through addition of new force-generating units. Here we use a guinea-pig model to show that hESC-CM grafts in injured hearts protect against arrhythmias and can contract synchronously with host muscle. Injured hearts with hESC-CM grafts show improved mechanical function and a significantly reduced incidence of both spontaneous and induced ventricular tachycardia. To assess the activity of hESC-CM grafts in vivo, we transplanted hESC-CMs expressing the genetically encoded calcium sensor, GCaMP3 (refs 4, 5). By correlating the GCaMP3 fluorescent signal with the host ECG, we found that grafts in uninjured hearts have consistent 1:1 host–graft coupling. Grafts in injured hearts are more heterogeneous and typically include both coupled and uncoupled regions. Thus, human myocardial grafts meet physiological criteria for true heart regeneration, providing support for the continued development of hESC-based cardiac therapies for both mechanical and electrical repair.

Concepts: Myocardial infarction, Cardiology, Heart, Muscle, Cardiac muscle, Cardiac electrophysiology, Muscular system, Ventricular fibrillation

167

Aim: To determine the effect of a 12-month intent-to-treat tesosterone replacement therapy (TRT) trial on QTa interval variability (QTaVI) in hypogonadal (HG) men with spinal cord injury (SCI). Method: A prospective, controlled, 12-month TRT trial was completed in twenty-two healthy, chronic, non-ambulatory men with SCI. Based on serum T concentration, subjects were designated as HG (≤11.3 nmol/l) or eugonadal (EG, ≥11.4 nmol/l). Digital 3-lead electrocardiograms were performed. Heart rate (RR), heart rate variability [(HRV), including total power (TP(RR)), low frequency (LF(RR)) and high freguency (HF(RR))], QTa, QTe, and RT intervals, QTC (Bazett), QTVN, and QTaVI were calculated and evaluated at baseline and 12 months. Lipoprotein profiles (triglycerides, total cholesterol, low density and high-density lipoproteins) were obtained at the respective time points. Results: Based on serum T concentration, 13 subjects were designated as HG and 11 EG. During the trial, there were no group differences for RR, QTa, QTe or RT intervals, QTC, TP(RR), HF(RR), or lipoproteins. The HG was older (p < 0.05) and LF(RR) was lower (p < 0.05) at baseline. At baseline, QTaVI was significantly greater in HG compared to EG [-0.17 (0.92) vs. -1.07 (0.90); p < 0.05]. After TRT, this group difference was no longer present [-0.44 (0.87) vs. -0.65 (0.85)] and the change in HG was significant (p < 0.05). Conclusion: Hypogonadism in men with SCI was associated with elevated QTaVI at baseline. After 12 months of physiological TRT, the QTaVI improved in association with raising T into the normal range. These findings occurred independently from the prolongation of the QT interval.

Concepts: Cholesterol, Cardiology, Lipoprotein, Lipoproteins, Cardiac electrophysiology, Testosterone, QT interval, Hypogonadism

160

Persistent left superior vena cava (PLSVC) is present in about 0.3%-0.5% of the general population and in about 12% of patients with other abnormalities [1]. This congenital anomaly is usually asymptomatic and does not cause any physiological problems. However, it may become a significant problem in multiple clinical situations. Various complications related to PLVSC are encountered in anaesthesiological, nephrological, oncological and cardiological procedures. The presence of PLSVC is usually incidentally detected during placement of pacemaker (PM), implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) leads. Technical difficulties during lead positioning (especially ventricular leads) are commonly known and often described in the literature. The purpose of the present study was to evaluate the specific methods used for implantation of increasingly complicated pacing systems, finding an optimal strategy in patients with PLSVC, especially with electrotherapy complications.

Concepts: Implantable cardioverter-defibrillator, Cardiac electrophysiology, Magnetic resonance imaging, Vein, Inferior vena cava, Superior vena cava, Artificial pacemaker, Transcutaneous pacing

156

The Brugada syndrome (BrS) is a malignant, genetically-determined, arrhythmic syndrome manifesting as syncope or sudden cardiac death (SCD) in individuals with structurally normal hearts. The diagnosis of the BrS is mainly based on the presence of a spontaneous or Na + channel blocker induced characteristic, electrocardiographic (ECG) pattern (type 1 or coved Brugada ECG pattern) typically seen in leads V1 and V2 recorded from the 4th to 2nd intercostal (i.c.) spaces. This pattern needs to be distinguished from similar ECG changes due to other causes (Brugada ECG phenocopies). This review focuses mainly on the ECG-based methods for diagnosis and arrhythmia risk assessment in the BrS. Presently, the main unresolved clinical problem is the identification of those patients at high risk of SCD who need implantable cardioverter-defibrillator (ICD), which is the only therapy with proven efficacy. Current guidelines recommend ICD implantation only in patients with spontaneous type 1 ECG pattern, and either history of aborted cardiac arrest or documented sustained VT (class I), or syncope of arrhythmic origin (class IIa) because they are at high risk of recurrent arrhythmic events (up to 10% or more annually for those with aborted cardiac arrest). The majority of BrS patients are asymptomatic when diagnosed and considered to have low risk (around 0.5% annually) and therefore not indicated for ICD. The majority of SCD victims in the BrS, however, had no symptoms prior to the fatal event and therefore were not protected with an ICD. While some ECG markers such as QRS fragmentation, infero-lateral early repolarisation, and abnormal late potentials on signal-averaged ECG are known to be linked to increased arrhythmic risk, they are not sufficiently sensitive or specific. Potential novel ECG-based strategies for risk stratification are discussed based on computerised methods for depolarisation and repolarisation analysis, a composite approach targeting several major components of ventricular arrhythmogenesis, and the collection of large digital ECG databases in genotyped BrS patients and their relatives.

Concepts: Cardiology, Implantable cardioverter-defibrillator, Cardiac arrest, Cardiac electrophysiology, Ventricular fibrillation, Sudden cardiac death, Brugada syndrome, Cardiac dysrhythmia

150

The introduction of the so-called newer-generation transcatheter aortic valve implantation (TAVI) devices has led to a dramatic reduction in the incidence of complications associated with the procedure. However, preliminary data suggest that conduction abnormalities (particularly new-onset atrioventricular block and left bundle branch block) remain a frequent complication post TAVI. Although inconsistencies across studies are apparent, new-onset conduction abnormalities post TAVI may be associated with higher incidences of mortality, sudden cardiac death and left ventricular dysfunction. Strategies intended both to reduce the risk and to improve the management of such complications are clearly warranted. In fact, the indication and timing of permanent pacemaker implantation are frequently individualised according to centre and/or operator preference. Currently, studies assessing the impact of these complications and the optimal indications for permanent cardiac pacing are underway. In this article, we review the data available on the incidence and impact of conduction disturbances following TAVI, and propose a strategy for the management of such complications.

Concepts: Cardiology, Heart, Cardiac arrest, Cardiac electrophysiology, Left ventricle, Cardiac pacemaker, Sinoatrial node, Transcutaneous pacing

62

QT interval-prolonging drug-drug interactions (QT-DDIs) may increase the risk of life-threatening arrhythmia. Despite guidelines for testing from regulatory agencies, these interactions are usually discovered after drugs are marketed and may go undiscovered for years.

Concepts: Pharmacology, Drug, Cardiac electrophysiology, Drugs, Experiment