Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen\'s criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p < 0.05). In the MRI subsample, QT, QTc, JT, and JTc intervals were significantly associated with larger total WMH and PWMH volumes (p < 0.05), but not with DWMH volume. Statistical interactions were detected, such that prolonged QT and JT intervals were significantly associated with reduced GM volume only among participants with coronary heart disease or without APOE ε4 allele (p < 0.05). Prolonged ventricular repolarization is associated with MCI and cerebral microvascular lesions in a general population of older adults. This underlies the importance of cognitive assessments and brain MRI examination among older adults with prolonged QT interval.

The EMMY trial was a multicentre, investigator-initiated, placebo-controlled, double-blind trial, which enrolled 476 patients immediately following AMI and the first study demonstrating a significant reduction in NT-proBNP-levels as well as significant improvements in cardiac structure and function in patients after acute myocardial infarction treated with empagliflozin vs. placebo. However, hardly any data are available investigating the prognostic role of baseline electrocardiogram metrics in SGLT2-inhibitor-treated patients. This post-hoc analysis investigated the association of baseline ECG metrics collected in one centre of the trial (181 patients) with changes in structural and functional cardiac parameters as well as cardiac biomarkers in response to Empagliflozin treatment. A total of 181 patients (146 men; mean age 58 ± 14 years) were included. Median PQ-interval was 156 (IQR 144-174) milliseconds (ms), QRS width 92 (84-98) ms, QTc interval 453 (428-478) ms, Q-wave duration 45 (40-60) ms, Q-wave amplitude 0.40 (0.30-0.70) millivolt (mV), and heart rate was 71 (64-85) bpm. For functional cardiac parameters (LVEF and E/e\') of the entire cohort, a greater decrease of E/e\' from baseline to week 26 was observed in shorter QRS width (P = 0.005).Structural cardiac endpoints were only found to have a significant positive correlation between LVEDD and Q wave duration (P = 0.037). Higher heart rate was significantly correlated with better response in LVEF (P = 0.001), E/e\' (P = 0.021), and NT-proBNP (P = 0.005). Empagliflozin-treatment showed no interaction with the results. Baseline ECG characteristics post AMI are neither predictive for beneficial NTproBNP effects of Empagliflozin post AMI, nor for functional or structural changes within 26 weeks post AMI.

Our study retrospectively examines 51 non-rodent general toxicology studies conducted over the past 8 years to ascertain the influence of recording methodologies on baseline cardiovascular (CV) parameters and statistical sensitivity. Specifically, our work aims to evaluate the frequency of cardiovascular parameter recording categorized by therapeutic modality and study type, to assess the variability in these parameters based on measurement techniques, and to determine the sample sizes needed for detecting relevant changes in heart rate (HR), blood pressure (BP), and QTc interval in non-human primate (NHP) studies. Results indicate that electrocardiogram (ECG) measurements in dogs and NHP were recorded in 63% of studies, combined with BP recording in 18% of studies, while BP was never recorded alone. Trend analysis reveals a decline in the utilisation of restraint-based methods for ECG measurements post-2017, to the benefit of telemetry-based recordings, particularly Jacketed External Telemetry (JET). There was a marked difference in baseline values, with restraint-based methods showing significantly higher HR and QTc values compared to JET, likely linked to animal stress. Further analysis suggests an unrealistic and unethical sample size requirement in NHP studies for detecting biologically meaningful CV parameter changes using restraint-based methods, while JET methods necessitate significantly smaller sample sizes. This retrospective study indicates a notable shift from snapshots short-duration, restraint-based methods towards telemetry approaches over the recent years, especially with an increased usage of implanted telemetry. The transition contributes to potential consensus within industry or regulatory frameworks for optimal practices in assessing ECG, HR, and BP in general toxicology studies.

Secundum atrial septal defect (ASD2) detection is often delayed, with the potential for late diagnosis complications. Recent work demonstrated artificial intelligence-enhanced ECG analysis shows promise to detect ASD2 in adults. However, its application to pediatric populations remains underexplored. In this study, we trained a convolutional neural network (AI-pECG) on paired ECG-echocardiograms (≤ 2 days apart) to detect ASD2 from patients ≤ 18 years old without major congenital heart disease. Model performance was evaluated on the first ECG-echocardiogram pair per patient for Boston Children\'s Hospital internal testing and emergency department cohorts using area under the receiver operating (AUROC) and precision-recall (AUPRC) curves. The training cohort comprised of 92,377 ECG-echocardiogram pairs (46,261 patients; median age 8.2 years) with an ASD2 prevalence of 6.7%. Test groups included internal testing (12,631 patients; median age 7.4 years; 6.9% prevalence) and emergency department (2,830 patients; median age 7.5 years; 4.9% prevalence) cohorts. Model performance was higher in the internal test (AUROC 0.84, AUPRC 0.46) cohort than the emergency department cohort (AUROC 0.80, AUPRC 0.30). In both cohorts, AI-pECG outperformed ECG findings of incomplete right bundle branch block. Model explainability analyses suggest high-risk limb lead features include greater amplitude P waves (suggestive of right atrial enlargement) and V1 RSR\' (suggestive of RBBB). Our findings demonstrate the promise of AI-pECG to inexpensively screen and/or detect ASD2 in pediatric patients. Future multicenter validation and prospective trials to inform clinical decision making are warranted.

The skill of interpretation of the electrocardiogram (ECG) remains poor despite existing educational initiatives. We sought to evaluate the validity of using a subjective scoring system to assess the accuracy of ECG interpretations submitted by pediatric cardiology fellows, trainees, and faculty to the Pediatric ECG Review (pECGreview), a web-based ECG interpretation training program. We conducted a retrospective, cross-sectional study of responses submitted to pECGreview. ECG interpretations were assessed independently by four individuals with a range of experience. Accuracy was assessed using a 3-point scale: 100% for generally correct interpretations, 50% for over- or underdiagnosis of minor ECG abnormalities, and 0% for over- or underdiagnosis of major ECG abnormalities. Inter-rater agreement was assessed using expanded Bland-Altman plots, Pearson correlation coefficients, and Intraclass Correlation Coefficients (ICC). 1460 ECG interpretations by 192 participants were analyzed. 107 participants interpreted at least five ECGs. The mean accuracy score was 76.6 ± 13.7%. Participants were correct in 66.1 ± 5.1%, had minor over- or underdiagnosis in 21.5 ± 4.6% and major over- or underdiagnosis in 12.3 ± 3.9% of interpretations. Validation of agreement between evaluators demonstrated limits of agreement of 11.3%. Inter-rater agreement exhibited consistent patterns (all correlations ≥ 0.75). Absolute agreement was 0.74 (95% CI 0.69-0.80), and average measures agreement was 0.92 (95% CI 0.89-0.94). Accuracy score analysis of as few as five ECG interpretations submitted to pECGreview yielded good inter-rater reliability for assessing and ranking ECG interpretation skills in pediatric cardiology fellows in training.

Phosphoinositide 3-kinase (PI3K) inhibitors have shown synergistic anticancer effects with endocrine therapy against ER+/PIK3CA-mutated breast cancer. PI3K inhibitors for cancer therapy are becoming more common. There is an increasing need to understand their cardiac adverse events. In this report, we describe the features of near-fatal mixed arrhythmias in a patient who was undergoing a phase Ib clinical study of PI3Kα inhibitor with fulvestrant. Subsequently, the patient survived by cardiopulmonary resuscitation and therefore did not die. This case highlights that PI3K inhibitors can induce QT/QTc prolongation and predispose patients to TdP. The combination of QT/QTc prolongation in combination with prolonged cardiac repolarization, such as an AV block during treatment with PI3Kα inhibitor, may aggravate the occurrence of TdP. It is likely to be a safer strategy to adjust the standard of discontinuing drugs and continuing drugs (QTc interval was <500 and <60 ms at baseline) or choose other types of alternative treatment options. This report provided some ideas for clinicians to identify early and prevent the occurrence of fatal arrhythmias during anticancer treatment.

BACKGROUND: Pulmonary embolisms (PEs) exhibit clinical features similar to those of acute coronary syndrome (ACS), including electrocardiographic abnormalities and elevated troponin levels, which frequently lead to misdiagnoses in emergency situations.
METHODS: Here, we report a case of PE coinciding with chronic coronary syndrome in which the patient\'s condition was obscured by symptoms mimicking ACS. A 68-year-old female with syncope presented to the hospital. Upon admission, she was found to have elevated troponin levels and an electrocardiogram showing ST-segment changes across multiple leads, which initially led to a diagnosis of ACS. Emergency coronary arteriography revealed occlusion of the posterior branches of the left ventricle of the right coronary artery, but based on the complexity of the intervention, the occlusion was considered chronic rather than acute. On the 3rd day after admission, the patient experienced recurrent chest tightness and shortness of breath, which was confirmed as acute PE by emergency computed tomography pulmonary angiography. Following standardized anticoagulation treatment, the patient improved and was subsequently discharged.
CONCLUSIONS: This case report highlights the importance of recognizing the nonspecific features of PE. Clinicians should be vigilant when identifying other clinical features that are difficult to explain accompanying the expected disease, and it is necessary to carefully identify the causes to prevent missed diagnoses or misdiagnoses.

OBJECTIVE: Single-lead electrocardiograms (ECGs) can be recorded using widely available devices such as smartwatches and handheld ECG recorders. Such devices have been approved for atrial fibrillation (AF) detection. However, little evidence exists on the reliability of single-lead ECG interpretation. We aimed to assess the level of agreement on detection of AF by independent cardiologists interpreting single lead ECGs, and to identify factors influencing agreement.
METHODS: In a population-based AF screening study, adults aged ≥65 years old recorded four single-lead ECGs per day for 1-4 weeks using a handheld ECG recorder. ECGs showing signs of possible AF were identified by a nurse, aided by an automated algorithm. These were reviewed by two independent cardiologists who assigned participant- and ECG-level diagnoses. Inter-rater reliability of AF diagnosis was calculated using linear weighted Cohen\'s kappa (kw).
RESULTS: Out of 2,141 participants and 162,515 ECGs, only 1,843 ECGs from 185 participants were reviewed by both cardiologists. Agreement was moderate: kw = 0.48 (95% CI, 0.37-0.58) at participant-level; and kw = 0.58 (0.53-0.62) at ECG-level. At participant-level, agreement was associated with the number of adequate-quality ECGs recorded, with higher agreement in participants who recorded at least 67 adequate-quality ECGs. At ECG-level, agreement was associated with ECG quality and whether ECGs exhibited algorithm-identified possible AF.
CONCLUSIONS: Inter-rater reliability of AF diagnosis from single-lead ECGs was found to be moderate in older adults. Strategies to improve reliability might include participant and cardiologist training and designing AF detection programmes to obtain sufficient ECGs for reliable diagnoses.

UNASSIGNED: A notched P-wave is associated with the occurrence of atrial fibrillation (AF). However, the association between a notched P-wave and AF recurrence in patients who have undergone a catheter ablation for AF is unclear.
UNASSIGNED: We enrolled 100 subjects who underwent catheter ablation for AF (paroxysmal AF: 60 cases; persistent AF: 40 cases). Twelve-lead electrocardiography (ECG) was conducted, and the peak-to-peak distance in the M shape was calculated automatically using a 12-lead ECG analysis system. A notched P-wave was defined as a P-wave with an M-shape and a peak-to-peak distance of ≥20 ms in lead II. We compared the recurrence of AF in the patients with notched P-wave and the others.
UNASSIGNED: The mean follow-up period was 12 ± 8 months, and a recurrence of AF was observed in 28 patients. The recurrence of AF in the notched P-wave group was significantly higher than that in the controls (log rank 5.14, p = .023). A notched P-wave was a significant predictor of the recurrence of AF after adjustment for age, gender, history of heart failure, history of catheter ablation, persistent AF, use of antiarrhythmic drugs, and the left atrial volume index (hazard ratio 2.470, 95% confidence interval 1.065-5.728, p = .035).
UNASSIGNED: Automatically identified notched P-waves with peak-to-peak distance ≥20 ms were associated with AF recurrence in patients who had undergone catheter ablation.

BACKGROUND: We aimed to assess the efficacy of the neutrophil elastase inhibitor, sivelestat, in the treatment of sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM).
METHODS: Between January 2019 and December 2021, we conducted a randomized trial on patients who had been diagnosed with sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM) at Wuhan Union Hospital. The patients were divided into two groups by random envelop method, the Sivelestat group and the Control group. We measured the serum concentrations of Interleukin (IL)-6, IL-8, Tumor necrosis factor-α (TNF-α), and High-mobility group box 1 (HMGB1) at five time points, which were the baseline, 12 h, 24 h, 48 h, and 72 h after admission to the ICU. We evaluated the cardiac function by sonography and the heart rate variability (HRV) with 24-hour Holter recording between the time of admission to the intensive care unit (ICU) and 72 h after Sivelestat treatment.
RESULTS: From January 2019 to December 2021, a total of 70 patients were included in this study. The levels of IL-6, IL-8, and TNF-α were significantly lower in the Sivelestat group at different time points (12 h, 24 h, 48 h, and 72 h). HMGB1 levels were significantly lower at 72 h after Sivelestat treatment (19.46 ± 2.63pg/mL vs. 21.20 ± 2.03pg/mL, P = 0.003). The stroke volume (SV), tricuspid annular plane systolic excursion (TAPSE), early to late diastolic transmitral flow velocity (E/A), early (e\') and late (a\') diastoles were significantly low in the Control group compared with the Sivelestat group. Tei index was high in the Control group compared with the Sivelestat group (0.60 ± 0.08 vs. 0.56 ± 0.07, P = 0.029). The result of HRV showed significant differences in standard deviation of normal-to-normal intervals (SDNN), low frequency (LF), and LF/HF (high frequency) between the two groups.
CONCLUSIONS: Sivelestat can significantly reduce the levels of serum inflammatory factors, improve cardiac function, and reduce heart rate variability in patients with Sepsis-induced ARDS and SCM.