Eleclazine Suppresses Ventricular Fibrillation in Failing Rabbit Hearts with Ischemia- Reperfusion Injury Undergoing Therapeutic Hypothermia.

INTRODUCTION: Eleclazine is a highly selective late sodium current inhibitor, possibly effective in reducing ventricular fibrillation (VF) in heart failure (HF) with ischemia-reperfusion (IR) injury. The electrophysiological effects of eleclazine at therapeutic hypothermia (TH) are unknown. We investigated the effects of eleclazine in suppressing VF in failing rabbit hearts with IR injury undergoing TH. METHOD: HF was induced by right ventricular pacing. An IR model was created using coronary artery ligation for 60 min, followed by reperfusion for 30 min. Hearts were excised and Langendorff-perfused for optical mapping and electrophysiological studies. Electrophysiological studies were repeated after TH (33 oC) for 30 min or eleclazine (1 µM) infusion for 20 min. RESULTS: In failing IR-injured hearts, eleclazine reduced action potential duration (APD) dispersion and accelerated intracellular Ca2+ uptake to suppress arrhythmogenic alternans, but also exacerbated rate-dependent conduction slowing, resulting in neutral effects on VF inducibility at normothermia. TH increased VF severity. Eleclazine after TH ameliorated TH-induced APD dispersion and further depressed conduction to reduce VF inducibility and severity. TH after eleclazine also slowed conduction to a greater extent to reduce VF inducibility and severity by extrastimulus pacing. In control IR-injured hearts, eleclazine increased VF severity by dynamic pacing at normothermia, which was counteracted by TH. CONCLUSIONS: Eleclazine does not prevent VF at normothermia, but reduces VF inducibility and severity by extrastimulus pacing at TH in isolated failing hearts with regional IR injury.

Vericiguat suppresses ventricular tachyarrhythmias inducibility in a rabbit myocardial infarction model.

BACKGROUND: The VICTORIA trial demonstrated a significant decrease in cardiovascular events through vericiguat therapy. This study aimed to assess the potential mechanisms responsible for the reduction of cardiovascular events with vericiguat therapy in a rabbit model of myocardial infarction (MI). METHODS: A chronic MI rabbit model was created through coronary artery ligation. Following 4 weeks, the hearts were harvested and Langendorff perfused. Subsequently, electrophysiological examinations and dual voltage-calcium optical mapping studies were conducted at baseline and after administration of vericiguat at a dose of 5 µmol/L. RESULTS: Acute vericiguat therapy demonstrated a significant reduction in premature ventricular beat burden and effectively suppressed ventricular arrhythmic inducibility. The electrophysiological influences of vericiguat therapy included an increased ventricular effective refractory period, prolonged action potential duration, and accelerated intracellular calcium (Cai) homeostasis, leading to the suppression of action potential and Cai alternans. The pacing-induced ventricular arrhythmias exhibited a reentrant pattern, attributed to fixed or functional conduction block in the peri-infarct zone. Vericiguat therapy effectively mitigated the formation of cardiac alternans as well as the development of reentrant impulses, providing additional anti-arrhythmic benefits. CONCLUSIONS: In the MI rabbit model, vericiguat therapy demonstrates anti-ventricular arrhythmia effects. The vericiguat therapy reduces ventricular ectopic beats, inhibiting the initiation of ventricular arrhythmias. Furthermore, the therapy successfully suppresses cardiac alternans, preventing conduction block and, consequently, the formation of reentry circuits.

Comparing Artificial Intelligence-Enabled Electrocardiogram Models in Identifying Left Atrium Enlargement and Long-term Cardiovascular Risk.

BACKGROUND: The role of P-wave in identifying left atrial enlargement (LAE) with the use of artificial intelligence (AI)-enabled electrocardiography (ECG) models is unclear. It is also unknown if AI-enabled single-lead ECG could be used as a diagnostic tool for LAE surveillance. We aimed to build AI-enabled P-wave and single-lead ECG models to identify LAE using sinus rhythm (SR) and non-SR ECGs, and compare the prognostic ability of severe LAE, defined as left atrial diameter ≥ 50 mm, assessed by AI-enabled ECG models vs echocardiography. METHODS: This retrospective study used data from 382,594 consecutive adults with paired 12-lead ECG and echocardiography performed within 2 weeks of each other at Chang Gung Memorial Hospital. UNet++ was used for P-wave segmentation. ResNet-18 was used to develop deep convolutional neural network-enabled ECG models for discriminating LAE. External validation was performed with the use of data from 11,753 patients from another hospital. RESULTS: The AI-enabled 12-lead ECG model outperformed other ECG models for classifying LAE, but the single-lead ECG models also showed excellent performance at a left atrial diameter cutoff of 50 mm. AI-enabled ECG models had excellent and fair discrimination on LAE using the SR and the non-SR data set, respectively. Severe LAE identified by AI-enabled ECG models was more predictive of future cardiovascular disease than echocardiography; however, the cumulative incidence of new-onset atrial fibrillation and heart failure was higher in patients with echocardiography-severe LAE than with AI-enabled ECG-severe LAE. CONCLUSIONS: P-Wave plays a crucial role in discriminating LAE in AI-enabled ECG models. AI-enabled ECG models outperform echocardiography in predicting new-onset cardiovascular diseases associated with severe LAE.

Machine learning-based prediction of acute mortality in emergency department patients using twelve-lead electrocardiogram.

Background: The risk of mortality is relatively high among patients who visit the emergency department (ED), and stratifying patients at high risk can help improve medical care. This study aimed to create a machine-learning model that utilizes the standard 12-lead ECG to forecast acute mortality risk in ED patients. Methods: The database included patients who visited the EDs and underwent standard 12-lead ECG between October 2007 and December 2017. A convolutional neural network (CNN) ECG model was developed to classify survival and mortality using 12-lead ECG tracings acquired from 345,593 ED patients. For machine learning model development, the patients were randomly divided into training, validation and testing datasets. The performance of the mortality risk prediction in this model was evaluated for various causes of death. Results: Patients who visited the ED and underwent one or more ECG examinations experienced a high incidence of 30-day mortality [18,734 (5.42%)]. The developed CNN model demonstrated high accuracy in predicting acute mortality (hazard ratio 8.50, 95% confidence interval 8.20-8.80) with areas under the receiver operating characteristic (ROC) curve of 0.84 for the 30-day mortality risk prediction models. This CNN model also demonstrated good performance in predicting one-year mortality (hazard ratio 3.34, 95% confidence interval 3.30-3.39). This model exhibited good predictive performance for 30-day mortality not only for cardiovascular diseases but also across various diseases. Conclusions: The machine learning-based ECG model utilizing CNN screens the risks for 30-day mortality. This model can complement traditional early warning scoring indexes as a useful screening tool for mortality prediction.

Long-term efficacy of sodium-glucose cotransporter 2 inhibitor therapy in preventing atrial fibrillation recurrence after catheter ablation in type 2 diabetes mellitus patients.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce new-onset atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM). We aimed to determine the long-term effects of SGLT2i on atrial tachyarrhythmia recurrence after catheter ablation (CA) in T2DM patients. Methods: This retrospective study enrolled consecutive patients with T2DM undergoing CA for AF between January 2016 and December 2021. Patient baseline demographic characteristics and use of anti-diabetic and anti-arrhythmic medications were analyzed. Echocardiographic parameters were obtained one day and 6 months after CA. Results: Our study population comprised 122 patients (70% paroxysmal AF). The baseline patient characteristics were similar between the SGLT2i-treated group (n = 45) and the non-SGLT2i-treated group (n = 77) except for stroke. At 6-month follow-up, body-mass index (BMI) was significantly decreased and left ventricular ejection fraction (LVEF) was significantly increased only in the SGLT2i group. E/e' was decreased 6 months after CA in both groups. During a mean follow-up of 33.7 ± 21.6 months, 22 of 122 patients had atrial tachyarrhythmia recurrence. The long-term atrial tachyarrhythmia-free survival rate was significantly higher in the SGLT2i-treated patients, and multivariate analysis revealed that AF type and SGLT2i use were independently associated with atrial tachyarrhythmia recurrence after CA. Conclusion: The use of SGLT2i and AF type were independent risk factors associated with atrial tachyarrhythmia recurrence after CA in T2DM patients with AF. This result was at least partly due to the pleiotropic effects of SGLT2i on BMI reduction and left ventricular function improvement.

Artificial intelligence-enabled electrocardiographic screening for left ventricular systolic dysfunction and mortality risk prediction.

Background: Left ventricular systolic dysfunction (LVSD) characterized by a reduced left ventricular ejection fraction (LVEF) is associated with adverse patient outcomes. We aimed to build a deep neural network (DNN)-based model using standard 12-lead electrocardiogram (ECG) to screen for LVSD and stratify patient prognosis. Methods: This retrospective chart review study was conducted using data from consecutive adults who underwent ECG examinations at Chang Gung Memorial Hospital in Taiwan between October 2007 and December 2019. DNN models were developed to recognize LVSD, defined as LVEF <40%, using original ECG signals or transformed images from 190,359 patients with paired ECG and echocardiogram within 14 days. The 190,359 patients were divided into a training set of 133,225 and a validation set of 57,134. The accuracy of recognizing LVSD and subsequent mortality predictions were tested using ECGs from 190,316 patients with paired data. Of these 190,316 patients, we further selected 49,564 patients with multiple echocardiographic data to predict LVSD incidence. We additionally used data from 1,194,982 patients who underwent ECG only to assess mortality prognostication. External validation was performed using data of 91,425 patients from Tri-Service General Hospital, Taiwan. Results: The mean age of patients in the testing dataset was 63.7 ± 16.3 years (46.3% women), and 8,216 patients (4.3%) had LVSD. The median follow-up period was 3.9 years (interquartile range 1.5-7.9 years). The area under the receiver-operating characteristic curve (AUROC), sensitivity, and specificity of the signal-based DNN (DNN-signal) to identify LVSD were 0.95, 0.91, and 0.86, respectively. DNN signal-predicted LVSD was associated with age- and sex-adjusted hazard ratios (HRs) of 2.57 (95% confidence interval [CI], 2.53-2.62) for all-cause mortality and 6.09 (5.83-6.37) for cardiovascular mortality. In patients with multiple echocardiograms, a positive DNN prediction in patients with preserved LVEF was associated with an adjusted HR (95% CI) of 8.33 (7.71 to 9.00) for incident LVSD. Signal- and image-based DNNs performed equally well in the primary and additional datasets. Conclusion: Using DNNs, ECG becomes a low-cost, clinically feasible tool to screen LVSD and facilitate accurate prognostication.

Misspecification of a binary dependent variable in the logistic model controlling for the repeated longitudinal measures.

Many medical applications are interested to know the disease status. The disease status can be related to multiple serial measurements. Nevertheless, owing to various reasons, the binary outcome can be measured incorrectly. The estimators derived from the misspecified outcome can be biased. This paper derives the complete data likelihood function to incorporate both the multiple serial measurements and the misspecified outcome. Owing to the latent variables, EM algorithm is used to derive the maximum-likelihood estimators. Monte Carlo simulations are conducted to compare the impact of misspecification on the estimates. A retrospective data for the recurrence of atrial fibrillation is used to illustrate the usage of the proposed model.

Obstetric and fetal/neonatal outcomes in pregnant women with frequent premature ventricular complexes and structurally normal heart.

BACKGROUND: High premature ventricular complex (PVC) burden may increase the risk of left ventricular dysfunction and all-cause mortality. We aimed to evaluate maternal and neonatal outcomes of pregnant women with structurally normal heart having PVC burden ≥1%. METHODS: This retrospective cohort study used data from Chang Gung Research Database. Pregnancies from January 1, 2005, through June 30, 2020, with documented maternal PVC burden ≥1% by 24-h Holter monitor were identified. Pregnant women with a diagnosis of structural heart disease or arrhythmias other than PVC were excluded. We used propensity score matching (PSM) to balance the covariates between the PVC group and normal control group. The PVC group was classified into low-PVC (<10%) and high-PVC burden subgroups. The maternal and neonatal outcomes were assessed through 6 months after delivery or termination. RESULTS: After PSM, there were 214, 61, and 46 pregnant women enrolled in the normal control group, low-PVC burden, and high-PVC burden subgroups, respectively. The high-PVC and low-PVC burden subgroups had composite adverse maternal and neonatal events similar to the control group without use of antiarrhythmic drugs (AADs), but a higher proportion of placental abruption was observed in the high-PVC burden subgroup. Maternal age, diabetes, and overweight were significant predictors of composite adverse maternal events, whereas only maternal age was a significant predictor of composite adverse neonatal events. CONCLUSIONS: High PVC burden was not associated with poor composite adverse maternal and neonatal outcomes with no need of AADs therapy in pregnant women with structurally normal heart.

Left atrial booster-pump function as a predictive parameter for atrial fibrillation in patients with severely dilated left atrium.

Background: Left atrial (LA) dimension ≥50 mm had approximately four times the risk of developing atrial fibrillation (AF). The aim of this study was to investigate whether the application of clinical and echocardiographic parameters could differentiate between the patients having severely dilated left atrium with and without AF. Methods: This retrospective cross-sectional study enrolled consecutive patients with LA dimension ≥50 mm and divided them into three groups: no AF (no-AF), paroxysmal AF (PAF) and non-paroxysmal AF (non-PAF) groups. For PAF and non-PAF groups, all patients underwent radiofrequency ablation, and the echocardiographic parameters were obtained on the next day after ablation. Results: Our study population comprised 160 patients, including 80, 53, and 27 patients in the non-AF, PAF and non-PAF groups, respectively. The no-AF group had a significantly higher body mass index (kg/m2) (29.31±6.27, 27.58±4.12 and 26.57±2.81, P=0.01), and a higher prevalence of diabetes mellitus (DM) [31 (38.80%), 13 (25.00%) and 4 (14.80%), P=0.01] and hypertension [67 (83.80%), 34 (65.40%), and 19 (70.40%), P=0.04], but a lower prevalence of rheumatic heart disease (RHD) [3 (3.80%), 6 (11.50%) and 5 (18.50%), P=0.02] and sick sinus syndrome [0 (0.00%), 6 (11.50%) and 4 (14.80%), P=0.045]. Echocardiographic studies showed that the non-AF group had significantly smaller LA minimal volume index (24.89±9.74, 34.06±19.38 and 42.83±17.44 mL/m2, P<0.01), higher LA emptying fraction (51.99%±13.97%, 38.40%±15.96% and 33.89%±10.73%, P<0.01), longitudinal strain (23.87%±7.72%, 17.11%±8.52% and 12.38%±4.28%, P<0.01) and strain rate than the AF groups. The multivariate analysis showed that the late diastolic component of LA strain rate was the only independent factor associated with the presence of AF (odds ratio, 21.69; 95% CI, 9.77-48.13, P<0.01). Conclusions: LA function plays an important role in the absence of AF in patients with LA dimension ≥50 mm; the late diastolic component of LA strain rate was the only independent variable on multivariate analysis.

Atrial fibrillation detection using ambulatory smartwatch photoplethysmography and validation with simultaneous holter recording.

BACKGROUND: Atrial fibrillation (AF)-associated embolic stroke is preventable, and AF detection may help to prevent stroke in subjects with paroxysmal AF. We aimed to evaluate the AF detection performance of smartwatch photoplethysmography (PPG) and the feasibility of ambulatory monitoring for AF detection in the daily life. DESIGN AND METHODS: Consecutive subjects who underwent ambulatory Holter electrocardiogram (ECG) monitoring for AF detection or AF burden evaluation were enrolled. The participants underwent 24 hours of simultaneous Holter ECG monitoring and continuous PPG recording using a Garmin smartwatch. The PPG signals were processed for noise rejection, beat detection, beat labeling, and rhythm labeling for each 5-minute segment. The accuracy of the PPG AF detection was calculated using the corresponding simultaneous Holter ECG as the AF diagnostic standard. RESULTS: Among the 200 available participants, 112 participants (56%) developed AF (the AF group). The sensitivity, specificity, and positive predicted value of AF detection in participants were 97.3%, 88.6%, and 91.6%, respectively. The area under the receiver operating characteristic curve was 0.90. When the performance was analyzed in these 5-minute segments, the sensitivity, specificity, and positive predicted values of AF detection were 97.1%, 86.8%, and 89.7%, respectively. CONCLUSIONS: This study demonstrated the feasibility of ambulatory monitoring for AF detection using a commercial smartwatch in daily life. A smartwatch may be an alternative screening tool to standard ambulatory Holter monitoring.

From Left Atrial Dimension to Curved M-Mode Speckle-Tracking Images: Role of Echocardiography in Evaluating Patients with Atrial Fibrillation.

Left atrial (LA) enlargement and dysfunction increase the risk of atrial fibrillation (AF). Traditional echocardiographic evaluation of the left atrium has been limited to dimensional and semi-quantification measurement of the atrial component of ventricular filling, with routine measurement of LA function not yet implemented. However, functional parameters, such as LA emptying fraction (LAEF), may be more sensitive markers for detecting AF-related changes than LA enlargement. Speckle-tracking echocardiography has proven to be a feasible and reproducible technology for the direct evaluation of LA function. The clinical application, advantages, and limitations of LA strain and strain rate need to be fully understood. Furthermore, the prognostic value and utility of this technique in making therapeutic decisions for patients with AF need further elucidation. Deep learning neural networks have been successfully adapted to specific tasks in echocardiographic image analysis, and fully automated measurements based on artificial intelligence could facilitate the clinical diagnostic use of LA speckle-tracking images for classification of AF ablation outcome. This review describes the fundamental concepts and a brief overview of the prognostic utility of LA size, LAEF, LA strain and strain rate analyses, and the clinical implications of the use of these measures.

Clinical Outcomes of low-voltage area-guided left atrial linear ablation for non-paroxysmal atrial fibrillation patients.

BACKGROUND: The therapeutic effect of low-voltage area (LVA)-guided left atrial (LA) linear ablation for non-paroxysmal atrial fibrillation (non-PAF) is uncertain. We aimed to investigate the efficacy of LA linear ablation based on the preexisting LVA and its effects on LA reverse remodeling in non-PAF patients. METHODS: We retrospectively evaluated 145 consecutive patients who underwent radiofrequency catheter ablation for drug-refractory non-PAF. CARTO-guided bipolar voltage mapping was performed in atrial fibrillation (AF). LVA was defined as sites with voltage ≤ 0.5 mV. If circumferential pulmonary vein isolation couldn't convert AF into sinus rhythm, additional LA linear ablation was performed preferentially at sites within LVA. RESULTS: After a mean follow-up duration of 48 ± 33 months, 29 of 145 patients had drugs-refractory AF/LA tachycardia recurrence. Low LA emptying fraction, large LA size and high extent of LVA were associated with AF recurrence. There were 136 patients undergoing LA linear ablation. The rate of linear block at the mitral isthmus was significantly higher via LVA-guided than non-LVA-guided linear ablation. Patients undergoing LVA-guided linear ablation had larger LA size and higher extent of LVA, but the long-term AF/LA tachycardia-free survival rate was higher than the non-LVA-guided group. The LA reverse remodeling effects by resuming sinus rhythm were noted even in patients with a diseased left atrium undergoing extensive LA linear ablation. CONCLUSIONS: LVA-guided linear ablation through targeting the arrhythmogenic LVA and reducing LA mass provides a better clinical outcome than non-LVA guided linear ablation, and outweighs the harmful effects of iatrogenic scaring in non-PAF patients.

P wave duration ≥150 ms predicts poor left atrial function and ablation outcomes in non-paroxysmal atrial fibrillation.

BACKGROUND: It remains unknown whether P wave duration (PWD) ≥ 150 ms measured after extensive radiofrequency catheter ablation (RFCA) can identify non-paroxysmal atrial fibrillation (non-PAF) patients at increased risk of atrial tachyarrhythmia recurrence. We investigated the predicting power of PWD and its association with left atrial (LA) reverse remodeling in patients with non-PAF undergoing pulmonary vein isolation with LA linear ablation. METHODS: We retrospectively evaluated 136 patients who underwent RFCA for drug-refractory non-PAF. Electroanatomic mapping was acquired during AF. Low-voltage area (LVA) was defined as an area with bipolar voltage ≤0.5 mV. Electrocardiography and echocardiography were performed during sinus rhythm 1 day and 3 months after RFCA. PWD was measured using amplified 12­lead electrocardiography. Prolonged PWD was defined as maximum PWD ≥ 150 ms. RESULTS: Over a mean follow-up duration of 48 ± 35 months, 28 patients experienced atrial tachyarrhythmia recurrence. PWD was positively correlated with LVA (r = 0.527, p < 0.001) and inversely correlated with LA emptying fraction (r = -0.399, p < 0.001). PWD was shortened and LA emptying fraction (LAEF) was increased in patients without atrial tachyarrhythmia recurrence during follow-up. Atrial tachyarrhythmia-free survival was significantly more likely in patients without a prolonged PWD (83.5% vs 60.7%, p = 0.002). Multivariate analysis showed that LAEF and PWD were independent predictors of atrial tachyarrhythmia recurrence. CONCLUSIONS: PWD ≥ 150 ms measured after RFCA can identify patients with non-PAF at increased risk of atrial tachyarrhythmia recurrence. PWD is correlated with LVA and LAEF and reflects LA reverse remodeling.

Beneficial Electrophysiological Effects of Rotigaptide Are Unable to Suppress Therapeutic Hypothermia-Provoked Ventricular Fibrillation in Failing Rabbit Hearts With Acute Ischemia-Reperfusion Injury.

Aims: Whether therapeutic hypothermia (TH) is proarrhythmic in preexisting failing hearts with acute ischemia-reperfusion (IR) injury is unknown. Additionally, the effectiveness of rotigaptide on improving conduction slowing in hearts with IR injury is ambiguous. We investigated the electrophysiological effects of TH and rotigaptide in failing rabbit hearts with acute IR injury and determined the underlying molecular mechanisms. Methods and Results: Heart failure was induced by right ventricular pacing (320 beats/min, 4 weeks). Rabbits with pacing-induced heart failure were randomly divided into TH (n = 14) and non-TH (n = 7) groups. The IR rabbit model was created by ligating the coronary artery for 60 min, followed by reperfusion for 15 min in vivo. Then, the hearts were excised quickly and Langendorff-perfused for simultaneous voltage and intracellular Ca2+ (Cai) optical mapping. Electrophysiological studies were conducted, and vulnerability to ventricular fibrillation (VF) was evaluated using pacing protocols. TH (33°C) was instituted after baseline studies, and electrophysiological studies were repeated. Rotigaptide (300 nM) was infused for 20 min, and electrophysiological studies were repeated under TH. Cardiac tissues were sampled for Western blotting. TH increased the dispersion and beat-to-beat variability of action potential duration (APD), aggravated conduction slowing, and prolonged Cai decay to facilitate spatially discordant alternans (SDA) and VF induction. Rotigaptide reduced the dispersion and beat-to-beat variability of APD and improved slowed conduction to defer the onset of arrhythmogenic SDA by dynamic pacing and elevate the pacing threshold of VF during TH. However, the effect of rotigaptide on TH-enhanced VF inducibility was statistically insignificant. TH attenuated IR-induced dysregulation of protein expression, but its functional role remained uncertain. Conclusion: Therapeutic hypothermia is proarrhythmic in failing hearts with acute IR injury. Rotigaptide improves TH-induced APD dispersion and beat-to-beat variability and conduction disturbance to defer the onset of arrhythmogenic SDA and elevate the VF threshold by dynamic pacing, but these beneficial electrophysiological effects are unable to suppress TH-enhanced VF inducibility significantly.

Enhanced detection of cardiac arrhythmias utilizing 14-day continuous ECG patch monitoring.

BACKGROUND: To evaluate the performance of a single­lead, 14-day continuous electrocardiogram (ECG) patch for the detection of arrhythmias compared to conventional 24-h monitoring. METHODS: This prospective clinical trial enrolled patients suspected of arrhythmias but not diagnosed by 12­lead ECGs. Each patient underwent a 24-h Holter and 14-day ECG patch simultaneously. Seven types of arrhythmias were classified: supraventricular tachycardia (SVT, repetitive atrial beats >4 beats), irregular SVT without P wave (>4 beats), AF/AFL (irregular SVT without P wave ≥30 s), pause ≥3 s, atrioventricular block (AVB; Mobitz type II, third-degree, two to one or high degree AVB), ventricular tachycardia (VT), and polymorphic VT. RESULTS: A total of 158 patients were recruited (mean wear time:12.3 ± 3.2 days). The overall arrhythmia detection rate was higher with 14-day ECG patches (59.5%) compared to 24-h Holter (19.0%, P < 0.001). Up to 87.2% of arrhythmias recorded with 14-day ECG patches were not associated with symptoms. The 14-day ECG patch was associated with higher detection rates compared to the 24-h Holter in patients with SVT (52.5% versus 15.8%, P < 0.001), irregular SVT without P wave (12.7% versus 4.4%, P = 0.002), AF/AFL (9.5% versus 3.8%, P = 0.042), and critical arrhythmias (pause ≥3 s, AVB, VT, polymorphic VT) (16.5% versus 2.5%, P < 0.001). The 14-day ECG patch detected more than 2 types of arrhythmias in 5.1% of patients. No serious adverse events in patients wearing the 14-day ECG patch were reported. CONCLUSIONS: The 14-day ECG patch outperformed 24-h Holter to detect overall, asymptomatic, critical and multiple arrhythmias. It is safe and has the potential to identify individuals with hidden arrhythmias, especially those with critical arrhythmias.

Mechanisms of ranolazine pretreatment in preventing ventricular tachyarrhythmias in diabetic db/db mice with acute regional ischemia-reperfusion injury.

Studies have demonstrated that diabetic (db/db) mice have increased susceptibility to myocardial ischemia-reperfusion (IR) injury and ventricular tachyarrhythmias (VA). We aimed to investigate the antiarrhythmic and molecular mechanisms of ranolazine in db/db mouse hearts with acute IR injury. Ranolazine was administered for 1 week before coronary artery ligation. Diabetic db/db and control db/+ mice were divided into ranolazine-given and -nongiven groups. IR model was created by 15-min left coronary artery ligation and 10-min reperfusion. In vivo electrophysiological studies showed that the severity of VA inducibility was higher in db/db mice than control (db/ +) mice. Ranolazine suppressed the VA inducibility and severity. Optical mapping studies in Langendorff-perfused hearts showed that ranolazine significantly shortened action potential duration, Cai transient duration, Cai decay time, ameliorated conduction inhomogeneity, and suppressed arrhythmogenic alternans induction. Western blotting studies showed that the expression of pThr17-phospholamban, calsequestrin 2 and voltage-gated sodium channel in the IR zone was significantly downregulated in db/db mice, which was ameliorated with ranolazine pretreatment and might play a role in the anti-arrhythmic actions of ranolazine in db/db mouse hearts with IR injury.