Prolonged Interval Research Articles

Evaluation of droperidol use in the emergency department: a retrospective analysis of QTc prolongation and adverse events

BackgroundDroperidol is a first-generation antipsychotic medication that has been used for various indications in the emergency department (ED); however, its use has been controversial due to reports of QT prolongation and the risk of torsades de pointes (TdP). The aim of the study is to evaluate the safety of droperidol administration in the ED.MethodsThis was a retrospective study, conducted at an academic level I trauma center. System-generated reports were used to identify all droperidol administrations in the ED from the time that droperidol was reintroduced to the institutional formulary on July 1, 2019 through January 31, 2023. The major safety endpoint was a composite of the incidence of QTc interval prolongation, incidence of TdP, ventricular arrhythmia, or hypotension.ResultsA total of 327 administrations of droperidol were identified in 245 patients in the ED. The composite safety endpoint occurred in 30 (9.1%) administrations. None of these events were classified as “probable” or “definite” on the Naranjo adverse drug reaction probability scale. No episodes of TdP or serious ventricular arrhythmia were reported. Higher cumulative droperidol dose and creatinine clearance < 60 mL/min were associated with an increased odds of developing QTc prolongation (OR 1.27 [CI 1.04–1.56]) and (OR 1.01 [CI 1.0-1.02]), respectively.ConclusionsThe study supports the use of low dose droperidol for various indications in the ED. There were no serious adverse events reported that could be directly attributed to droperidol use; however, it is crucial to consider the potential dose dependent impact on QTc prolongation.

Understanding ethnic inequalities in diagnostic intervals of cancer: a cohort study of patients presenting suspected cancer symptoms to general practitioners in England.

UK Asian and black patients experience longer cancer diagnostic intervals - period between initial symptomatic presentation in primary care and cancer diagnosis. To determine whether these differences are due to prolonged primary care intervals (period between first primary care presentation and secondary care referral), referral interval (period between referral and first secondary-care appointment) or secondary care interval (period between the first secondary care appointment and diagnosis). We conducted a cohort study of patients with seven common cancers (breast, lung, prostate, colorectal, oesophagogastric, myeloma, and ovarian), diagnosed after presenting symptoms in English primary care. Information on symptom presentation and cancer diagnosis was extracted from cancer registry-linked primary care data. Accelerated failure-time models were used to investigate ethnic differences across all four intervals. Across all sites, diagnostic intervals were longer for Asian and black patients compared to white patients. Site-specific analyses showed that, for myeloma, lung, prostate, and colorectal, the secondary care interval was longer in Asian and black patients who also had longer primary care interval in breast and colorectal cancer. There was little evidence of ethnic differences in referral interval. We found evidence of ethnic differences in diagnostic intervals, with prolonged secondary care intervals for four common cancers and prolonged primary care intervals for two. Although these differences are relatively modest, they are unjustified and may indicate shortcomings in healthcare delivery that disproportionately affect ethnic minorities.

Does COVID-19 impact the QT interval prolongation? Answers from genetic causal inference.

During the COVID-19 pandemic, there has been heightened interest in the QT interval, a crucial indicator of ventricular electrical activity. Mendelian randomization (MR) is used here to investigate the genetic causation between QT interval alterations and COVID-19. Genetic proxies representing three COVID-19 phenotypes-severe, hospitalized, and COVID-19-were identified in over 1,000,000 individuals of European ancestry. Univariate two-sample Mendelian randomization (TSMR) and multi-exposure-adjusted multivariate Mendelian randomization (MVMR) were used to assess genetic causal associations between COVID-19 and QT intervals in 84,630 UK Biobank participants. The MR-robust adjusted profile score (MR-RAPS) method and radial MR frame were utilized for effect robustness and outlier variant detection, with sensitivity analyses conducted to identify horizontal pleiotropy. For every COVID-19 phenotype, univariate TSMR analysis revealed non-significant causal estimates between COVID-19 and the QT interval [COVID-19: βIVW (95% CI): -0.44 (-1.72, 0.84), P = 0.50; hospitalization: βIVW: 0.12 (-0.57, 0.80), P = 0.74; severe case: βIVW: 0.11 (-0.29, 0.51), P = 0.58]. MR-RAPS and outlier-corrected radial MR analyses further supported this null causal estimation. In confounder-adjusted MVMR analysis, this nonsignificant causality was independent of BMI, smoking, and alcohol consumption [βBMI+Alcohol+Smoking (95% CI): -0.77 (-2.44, 0.91), P = 0.37]. Sensitivity analyses did not detect any evidence of bias from horizontal pleiotropy, abnormal data distribution, or weak instruments. These findings suggest that COVID-19 does not directly causally prolong the QT interval. Inconsistent findings in observational research may be attributed to residual confounding.

QTc interval prolongation and its associated factors among HIV infected patients on ART in Mettu Town

QTc interval prolongation, which is linked to cardiac arrhythmia and sudden cardiac death, is common in HIV-infected patients. This prolongation can be attributed to the side effects of antiretroviral medications, the direct impact of HIV on the heart, and chronic inflammatory responses that disrupt cardiac electrical activity. This study aimed at assessing QTc interval prolongation and associated factors among HIV-infected adults on ART. A cross-sectional study was conducted among consecutively selected 298 HIV-infected patients at Mettu Karl Specialized Hospital, southwest Ethiopia. A face-to-face interview with a structured and pretested questionnaire was employed to collect socio-demographic and behavioural characteristics data. Electrocardiography was done using a 12-lead electrocardiograph, and interpreted by a cardiologist. Data were entered into Epi-data version 4.6 and analyzed using SPSS version 25. Multivariable logistic regression analyses were done at a significance level of P < 0.05. QTc prolongation was prevalent in 12.4% of participants. Being on PIs containing HAART regimen (AOR = 5.7, 95%CI 2.54–12.8), having recent CD4 count of < 350 cells/mm3 (AOR = 4.8, 95%CI 2.19–10.5), and recent viral load of ≥ 1000coppies/ml (AOR = 2.8, 95%CI 1.24–6.42) were significantly associated with QTc prolongation. According to this study, one of the ten HIV-infected patients on ART had QTc prolongation. Therefore, we suggest that HIV-positive patients receiving treatment should undergo screening for QTc interval prolongation.

The QRS and T wave alternans — a new ECG pattern in Long QT syndrome

We present a case of a new ECG phenomenon that has not been described previously in patients with long QT syndrome (LQTS). Prolongation of the QT interval (QTc) to 568 ms were revealed in girl 6 years old on the resting ECG. There were no symptoms, syncope or family history of sudden death. A molecular genetic study revealed mutation «de novo» in the SCN5A gene (p.Val1411Met), a pathogenic class V that typical for the third molecular genetic variant of LQTS (LQT3). During Holter monitoring a «hyperadaptation» of the QT interval was noted (slope QT/RR 0.37 with normal limit till 0,24). New ECG pattern of the combination T wave alternans and QRS alternans (AT/AQRS) at the night sleep (possibly in REM sleep) were recorded. This pattern has not been described previously in patients with LQTS. Atenolol 1 mg/kg was prescribed. During therapy, AT/AQRS did not record after 2 months. Possible mechanisms and prognostic significance of the identified ECG pattern, issues of treatment of patients with LQT3 are discussed. Conclusions: Combined of T wave alternans and QRS alternans (AT/AQRS) is a new ECG pattern in patients with LQTS that is likely to increase the risk of cardiac events. “Hyperadaptation” of the QT interval may be one of the electrocardiological features of LQT3. The emergence of the AT/AQRS pattern during REM sleep makes this period perhaps the most dangerous for the development of cardiac events in patients with LQT3.

Prolonged interval hypofractionated radiotherapy facilitates better antitumor immunity.

To evaluate the impact of hypofractionated radiotherapy (Hypo-RT) with different interfraction intervals on tumor growth, immune response, and synergistic effects with anti-PD-1 immunotherapy. The mouse MC38 colon cancer model was utilized. Various radiation regimens were designed to investigate the effects of fraction interval and fraction size on tumor growth, immune mobilization, and combination effects with anti-PD-1 immunotherapy. For a fixed-dose experiment, the 6 × 5 Gy for every other day (qod) regimen demonstrated an equivalent effect on tumor growth compared to the 6 × 5 Gy once daily (qd) regimen, while the 6 × 5 Gy for twice weekly (biw) regimen failed to inhibit tumor growth. Both qod and biw regimens induced an enhanced immune response, unlike the qd regimen. For a fixed biologically equivalent dose experiment, 6 × 5 Gy qod, 4 × 7 Gy biw, and 2 × 11 Gy once weekly (qw) regimens exhibited similar tumor suppression to the 12 × 3 Gy qd regimen. The long-interval Hypo-RT regimens significantly mobilized host immunity, whereas 12 × 3 Gy qd did not. The peripheral and intratumoral T cells increased as the fraction interval and size increased. All Hypo-RT regimens combined with anti-PD-1 immunotherapy demonstrated higher intratumoral CD8 + T cells and more effective tumor growth delay compared to the 12 × 3 Gy qd regime. The current study suggested that a prolonged inter-fraction interval with an increased fraction size in Hypo-RT may be a promising option to balance the therapeutic effect on tumor and immune activation.

The Impact of Early Indication of Living Donor Liver Transplantation on the Outcomes of Patients With Propionic Acidemia: A Single-Center Experience.

Liver transplantation has been indicated for propionic acidemia (PA) patients with frequent metabolic decompensation and performed as an enzyme replacement therapy. We retrospectively evaluated the outcomes of patients with PA and analyze the appropriate timing of living donor liver transplantation (LDLT). We reviewed 12 children with PA who underwent LDLT, who were divided into early (period from the first episode of metabolic decompensation to LDLT < 1 year; n = 6) and late (> 1 year; n = 6) indication groups depending on the timing of LDLT. The patient and graft survival rates were 100% in 12 children with PA, and the median observation period was 61 months (5-193 months). None of the patients experienced any episodes of metabolic decompensation after LDLT. The timing of LDLT did not influence the incidence of surgical complications. Two patients in the late indication group had episodes of cardiac arrest and long QT syndrome before LDLT, and one patient showed prolongation of QT interval after LDLT. Two of the six patients in the late indication group had findings of metabolic stroke of the brain on MRI before LDLT. Although LDLT improved the findings of metabolic stroke, a decrease in development quotient score was shown in the post-LDLT course. LDLT may be an effective therapeutic option for improving metabolic control. Early LDLT might be help prevent cardiomyopathy and neurological impairment.

Electrophysiological predictors of susceptible atrial substrate for the onset and recurrence of atrial fibrillation.

The atrial electroanatomic substrate is an essential component in the pathogenesis of atrial fibrillation (AF). However, the electrophysiological markers of susceptible atria for AF are not well-characterized. This study aimed to assess atrial conduction indices on surface electrocardiogram (ECG) and intracardiac electrogram (EGM) as predictors of initiation and recurrence of AF after successful ablation. We studied all consecutive patients who underwent electrophysiological study and catheter ablation for AF (study group) or atrioventricular nodal reentrant tachycardia (AVNRT) (control group) from 2013 to 2018. Atrial conduction indices were measured on ECG and EGM during the electrophysiology study. Clinical data was obtained from the medical record. A total of 387 patients with AF (mean age 63years, 31% female) were studied and compared to 94 patents in control group. The initiation of AF was associated with significant prolongation of atrial conduction indices on ECG and EGM (p < 0.05). During a mean follow up of 5 ± 2years, recurrence of AF (48%) after successful ablation occurred in patients with prolonged P wave duration, left atrial (LA) conduction interval, proximal to distal coronary sinus (pCS-dCS) interval, and P wave to dCS interval (p < 0.05). Machine learning modeling determined that pCS-dCS interval, QRS duration, and LA duration in leads V1 and II are most impactful conduction indices in association with AF recurrence. Prolonged atrial conduction intervals, particularly LA (pCS-dCS), indicate susceptible substrate for the onset and the recurrence of AF after ablation. LA conduction indices can facilitate early detection and management of AF.

Long-read sequencing enables comprehensive molecular genetic diagnosis of Fabry disease

BackgroundThe clinical diagnosis of Fabry Disease (FD) can be challenging due to the clinical heterogeneity, especially in females. Patients with FD often experience a prolonged interval between the onset of symptoms and receiving a diagnosis. Genetic testing is the gold standard for precise diagnosis of FD, however conventional genetic testing could miss deep intronic variants and large deletions or duplications. Although next-generation sequencing, which analyzes numerous genes, has been successfully used for FD diagnosis and can detect complex variants, an effective and rapid tool for identifying a wide range of variants is imminent, contributing to decrease the diagnostic delay.MethodsThe comprehensive Analysis of FD (CAFD) assay was developed for FD genetic diagnosis, employing long-range PCR coupled with long-read sequencing to target the full-length GLA gene and its flanking regions. Its clinical performance was assessed through a comparative analysis with Sanger sequencing.ResultsGenetic testing was performed on 82 individuals, including 48 probands and 34 relatives. The CAFD assay additionally identified variants in two probands: one had a novel and de novo pathogenic variant with a 1715 bp insertion in intron 4, and the other carried two deep intronic VUS variants in cis-configuration also in intron 4. In total, CAFD identified 47 different variants among 48 probands. Of these, 42 (89.36%, 42/47) were pathogenic, while 5 (10.64%, 5/47) were VUS. Sixteen (34.04%, 16/47) of the variants were novel, including 15 SNV/Indels and one large intronic insertion. Pedigree analysis of 21 probands identified four de novo disease-causing variants. Hence, FD exhibits not only variable clinical presentations but also a wide spectrum of variants. Utilizing a comprehensive testing algorithm for diagnosing FD, which includes enzyme activity, clinical features, and genetic testing, the diagnostic yield of CAFD is 97.92% (47/48), which is higher than that of conventional Sanger sequencing, at 95.83% (46/48).ConclusionThe duration between initial clinical presentation and diagnosis remains long and winding. CAFD provides precise diagnosis for a wide spectrum of GLA variants, promoting timely diagnosis and appropriate treatment for FD patients.

The value of Hendry’s Score in predicting reduced ejection fraction in chronic heart failure patients with sinus rhythm

Objectives: To evaluate the role of Hendry’s score based on the electrocardiogram in predicting heart failure with reduced ejection fraction. Methods: This is a cross-sectional study, including 91 inpatient heart failure patients at the Vietnam Heart Institute, divided into two groups: heart failure with reduced left ventricular ejection fraction (EF ≤ 40 %) and heart failure with preserved left ventricular ejection fraction (EF ≥ 50%). The collected information included the general characteristics of the disease group (age, gender, etiology, clinical symptoms), blood test NT-proBNP, creatinine, electrolytes, echocardiogram, and electrocardiogram. Results: Forty-seven people were diagnosed with HFpEF, and 44 suffered from HFrEF. Multiple logistic regression analysis revealed certain ECG variables that were independent predictors of HFrEF, i.e., left atrial hypertrophy (LAH), QRS duration &gt; 100 ms, right bundle branch block (RBBB), ST-T segment changes, and prolongation of the QT interval. Based on Hendry’s Score, we obtained a score for HFpEF of -1 to +3. At the same time, HFrEF had a score of +4 to +6 with 81.3% sensitivity, 84% specificity, a 70.5% positive predictive value, an 87.2% negative predictive value, and an accuracy of 86%. Conclusions: The scoring system derived from this study, including the presence or absence of LAH, QRS duration &gt; 100 ms, RBBB, ST-T segment changes, and prolongation of the QT interval can be used to predict the type of HF with satisfactory sensitivity and specificity.

Analysis of the Prognostic Impact of Heart Rate Deceleration Capacity on Type 2 Diabetes Mellitus with Ventricular Premature Contractions

At present, one of the greatest life-threatening risks for patients with type 2 diabetes is cardiovascular complications. According to relevant research, approximately 70% to 80% of these patients die due to cardiovascular disease. Compared to non-diabetic individuals, diabetic patients face a two- to four-fold higher risk of developing cardiovascular and cerebrovascular diseases, with vascular complications resulting in an average life expectancy reduction of about 12 years. Increasing evidence indicates that cardiovascular-related indicators become abnormal as early as the initial stages of type 2 diabetes. During this period, the likelihood of adverse cardiovascular events rises, and cardiac autonomic dysfunction (CAD) begins, disrupting the balance between the parasympathetic and sympathetic nervous systems and thereby increasing cardiovascular disease risk. Cardiac autonomic dysfunction is one of many severe complications, and ventricular premature contractions are common arrhythmias in patients with type 2 diabetes, often seen as key indicators of declining cardiac function. Continuous heart rate deceleration, observed as deceleration runs (DRs) in Holter ECGs, manifests as a gradual prolongation of consecutive RR intervals, an indicator useful in assessing cardiac autonomic neuropathy. Persistent hyperglycemia or pre-diabetic states are associated with coronary artery disease (CAD), and strict blood glucose control helps slow the progression of microvascular complications. HRV monitoring is an effective method for evaluating early-stage cardiovascular autonomic neuropathy (CAN), providing a quantitative assessment of autonomic function and aiding in diagnosing other vascular complications.

Attitudes towards risk-stratified breast cancer screening in Denmark – a qualitative study

BackgroundToday the prerequisites exist to initiate risk-stratified screening according to a woman’s individual risk of breast cancer as opposed to existing one-size-fits-all age-based programmes. This presupposes that the women accept having their personal risk score estimated and their screening intervals changed accordingly. Risk-stratified screening has not yet been implemented in any country, but in the future many European countries will very likely move towards more personalized screening.MethodsThis qualitative study among 46 women aged 50-69 years used an anthropological approach and interpretive description. Data was collected using semi-structured focus group interviews and telephone interviews. The interviews were analysed using systematic text condensation.ObjectiveThe aim of this study was to explore Danish women’s understanding of breast cancer risk and their attitudes towards the concept of risk-stratified breast cancer screening.ResultsThe women highly valued the current screening program, seeing regular mammograms as crucial for early detection. The women had good knowledge of the causes of breast cancer, but they had not given much thought to their own risk. They found a personalized screening approach more reliable than age-based screening, understanding that low risk is not the same as no risk just as high risk is not equal to ever developing breast cancer. Despite concerns about increased anxiety arising from knowing one’s risk, they appreciated the possibility of more frequent screenings for high-risk individuals.ConclusionIn general, the women showed acceptance of a new breast cancer screening concept estimating their personal risk score. Due to concerns about interval cancers and the prolonged screening intervals for women at low risk, offering more intensified screening for high-risk women may be less challenging than deescalating screening for low-risk women. Whether the expressed positive attitude and curious interest will translate into actual participation if implemented, remains to be investigated further in an ongoing Danish trial.

Efficacy and Safety of Combined Bedaquiline and Delamanid Use among Patients with Multidrug-Resistant Tuberculosis in Beijing, China

ObjectivesThe combined use of bedaquiline and delamanid (BDQ-DLM) is limited by an increased risk of prolonging the QTc interval. We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital. We aimed to present clinical efficacy and safety data for Chinese patients. MethodsThis case–control study included patients with multidrug-resistant tuberculosis (MDR-TB) treated with BDQ alone or BDQ plus DLM. ResultsA total of 96 patients were included in this analysis: 64 in the BDQ group and 32 in the BDQ + DLM group. Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM, 46 patients (71.9%) in the BDQ group and 29 (90.6%) in the BDQ-DLM group achieved sputum culture conversion during treatment. The rate of sputum culture conversion did not differ between the two groups. The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group. The most frequent adverse event was QTc interval prolongation; however, the frequency of adverse events did not differ between the groups. ConclusionIn conclusion, our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB. Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.

Bigeminy with Prolonged QT Interval as an Ominous Sign for Impending Torsades de Pointes: A Case Report

Introduction: Ventricular ectopic beats and corrected QT interval (QTc) prolongation are both relatively common entities that are typically benign. It is difficult to predict subsequent dysrhythmias from either electrocardiogram (ECG) feature. The combination of both features may better predict the risk of torsades de pointes. We highlight a case of torsades preceded by a bizarre bigeminal rhythm with QTc prolongation likely caused by memantine use and hypokalemia. Case Report: An 84-year-old female presented to the emergency department with a fall. A syncope workup revealed an ECG demonstrating bigeminy with a prolonged QTc interval. Several minutes after obtaining the ECG, the patient went into torsades. She had multiple subsequent cardiac arrests during the rest of her hospital stay. This case report details the importance of recognizing ventricular bigeminy in the context of QTc prolongation as a harbinger of torsades. Conclusion: While premature ventricular contractions including bigeminy may be a benign finding, when accompanied by prolonged QTc intervals, they warrant immediate investigation and treatment of potential underlying pathology to prevent torsades and subsequent cardiac arrest.

QTc interval prolongation impact on in-hospital mortality in acute coronary syndromes patients using artificial intelligence and machine learning

BackgroundPrediction of mortality in hospitalized patients is a crucial and important problem. Several severity scoring systems over the past few decades and machine learning models for mortality prediction have been developed to predict in-hospital mortality. Our aim in this study was to apply machine learning (ML) algorithms using QTc interval to predict in-hospital mortality in ACS patients and compare them to the validated conventional risk scores.ResultsThis study was retrospective, using supervised learning, and data mining. Out of a cohort of 500 patients admitted to a tertiary care hospital from September 2018 to August 2020, who presented with ACS. Prediction models for in-hospital mortality in ACS patients were developed using 3 ML algorithms. We employed the ensemble learning random forest (RF) model, the Naive Bayes (NB) model and the rule-based projective adaptive resonance theory (PART) model. These models were compared to one another and to two conventional validated risk scores; the Global Registry of Acute Coronary Events (GRACE) risk score and Thrombolysis in Myocardial Infarction (TIMI) risk score. Out of the 500 patients included in our study, 164 (32.8%) patients presented with unstable angina, 148 (29.6%) patients with non-ST-elevation myocardial infarction (NSTEMI) and 188 (37.6%) patients were having ST-elevation myocardial infarction (STEMI). 64 (12.8%) patients died in-hospital and the rest survived. Performance of prediction models was measured in an area under the receiver operating characteristic curve (AUC) ranged from 0.83 to 0.93 using all available variables compared to the GRACE score (0.9 SD 0.05) and the TIMI score (0.75 SD 0.02). Using QTc as a stand-alone variable yielded (0.67 SD 0.02) with a cutoff value 450 using Bazett’s formula, whereas using QTc in addition to other variables of personal and clinical data and other ECG variables, the result was 0.8 SD 0.04. Results of RF and NB models were almost the same, but PART model yielded the least results. There was no significant difference of AUC values after replacing the missing values and applying class balancer.ConclusionsThe proposed method can effectively predict patients at high risk of in-hospital mortality early in the setting of ACS using only clinical and ECG data. Prolonged QTc interval can be used as a risk predictor of in-hospital mortality in ACS patients.

Abstract 4136984: Low Occurence of Fetal Extranodal Findings and AV Interval Prolongation in Prospectively Followed High Titer Anti-Ro Pregnancies

. Background: Third-degree atrioventricular block (AVB) is the most common manifestation of Anti-Ro antibody associated fetal cardiac disease. Extranodal findings of isolated cardiac echogenicity, valvulitis with insufficiency and AV interval prolongation have been reported but not described in large prospective series. Aims: To report the occurrence and outcomes of extranodal findings in subjects followed prospectively since 2020 in STOP BLOQ (Surveillance and Treatment to Prevent Fetal AV block Likely to Occur Quickly) and the Registry for Neonatal Lupus (RNL). Methods: We reviewed fetal echo reports from pregnant STOP BLOQ and RNL Anti-Ro antibody subjects. Pregnancies with high (&gt;1000 EU for anti-Ro52 or 60) antibody titers measured in a core research lab underwent surveillance with home fetal heart rate monitoring (FHRM) 3x/day and weekly or bi-weekly fetal echos from 17- 26 gestational weeks. Low titer subjects underwent echo or no surveillance based on local site protocol. We evaluated cardiac function, effusions, cardiac echogenicity and its location, any tricuspid (TV) or mitral (MV) insufficiency trivial or &gt;trivial) and AV conduction times (&lt;150, 150-170 or &gt;170 ms) Results: Echo reports were available in 622 prospectively followed pregnancies (376 high (40/376 with a previously affected child) and 246 low-titer pregnancies. All had subjectively normal ventricular function and none had effusions. Seven fetuses, 2 low and 5 high titer at 19 (range 16.7-21.7) weeks demonstrated cardiac echogenicity (n=6), AV or semilunar valve insufficiency (n=2) or AV interval 150-170 ms (n=2) (Table). Subjects 1 and 2, both high titer and treated with prophylactic Plaquenil (400 mg/d before 10 gestational weeks), had prior fetal AVB. Subject #1 had normal AV conduction but MV and TV echogenicity and moderate insufficiency of both valves which resolved in days after IVIG and dexamethasone (dex) treatment, but 3° AVB developed at 19 weeks after dex wean. Subjects 2-7 received no treatment and extranodal findings did not progress to cardiac dysfunction or AVB. During the same time period, 10 high titer subjects developed 2° or 3° AVB. Conclusion: Anti-Ro associated extranodal findings are rare, occurring in 1% of pregnancies overall and in 5% of pregnancies with a previously affected child. Unlike AVB, extranodal findings can occur in low titer pregnancies. The role of treatment for isolated extranodal findings in the absence of cardiac dysfunction is unclear.

Clinical and genetic analysis of a case of Triadin knockout syndrome due to variant of TRDN gene and a literature review

To explore the genetic etiology and clinical phenotype of a child with Triadin knockout syndrome (TKOS), and to review the relevant literature of TKOS patients due to variants of TRDN gene. A child who was admitted to the Children's Hospital of Xi'an Jiaotong University on March 19, 2023 due to sudden cardiac arrest 3 days earlier was selected as the study subject. Peripheral blood samples (2 to 3 mL) were collected from the child and her parents for the extraction of genomic DNA and whole exome sequencing (WES). Pathogenic variants were searched from databases such as the Genome Aggregation Database (gnomAD) and Online Mendelian Inheritance in Man (OMIM), and were assessed based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Sanger sequencing was carried out for family validation of the pathogenic variants. Using keywords such as "arrhythmias" "TRDN" and "Triadin" both in Chinese and English, relevant literature on TKOS patients due to variants of the TRDN gene was retrieved from the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases, and the time of literature retrieval was set from January 1, 2012 to December 1, 2023. This study has been approved by the Ethics Committee of the Affiliated Children's Hospital of Xi'an Jiaotong University (No. 20230097), and informed consent was obtained from the parents of the child. The child had experienced syncope and cardiac arrest after exercise. Electrocardiographic examination revealed QTc interval prolongation, T-wave inversion in precordial leads V1-V3, polymorphic ventricular premature beat (VPB), and ventricular tachycardia (VT) along with increased heart rate. WES and Sanger sequencing revealed that the child has harbored a homozygous c.463del(p.E155Kfs*20) variant of the TRDN gene, for which both of the parents were heterozygous. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+PM2+PM3). The child was ultimately diagnosed with TKOS. In total 12 publications on TOKS cases caused by TRDN gene variants were retrieved, which involved 30 patients and 28 carriers of single heterozygous variant of the TRDN gene. Among the 30 TKOS patients, 20 had carried homozygous variants of the TRDN gene, and 10 had carried compound heterozygous variants, and all had exhibited significant clinical phenotype of arrhythmia, with most cases had experienced malignant arrhythmia induced by exercise and/or excitement during infancy or early childhood, leading to recurrent syncope and cardiac arrest. Of note, none of the 28 carriers of single heterozygous variant had abnormal clinical phenotype. The homozygous c.463del(p.E155Kfs20) variant of the TRDN gene probably underlay the pathogenesis of cardiac arrest in this child. Above discovery has enriched the mutational spectrum of the TRDN gene.

QTc interval prolongation and risk of atrial fibrillation recurrence: a meta-analysis and observational cohort study.

Corrected QT interval (QTc) is a ventricular repolarization marker on electrocardiography. Previous studies evaluated its value in predicting atrial fibrillation (AF) occurrence. However, its predictive efficacy for AF recurrence remains controversial. We searched PubMed and Google databases for studies before January 2024 evaluating the association between QTc interval and AF incidence. A meta-analysis of the eligible datasets was conducted using Bazett's formula, with subgroup analysis to explore the heterogeneity. Additionally, thirty-eight patients with AF who underwent radiofrequency catheter ablation were enrolled and followed-up for 3-36 months. Univariate and multivariate Cox models were used to calculate the hazard ratios (HRs) and determine the relationship between clinical factors and AF recurrence. Kaplan-Meier survival analysis and ROC curve were conducted to assess the impact and predictive efficacy of individual factors. Eleven datasets from nine eligible studies were enrolled and meta-analysed. We found that patients with prolonged QTc interval was associated with a significantly higher AF incidence risk, and the risk increased with every 10-ms prolongation. However, this association was not significant in the AF recurrence subgroup. In our prospective cohort, the preoperative body mass index, QTc, left atrial diameter (LAD), and uric acid levels influenced AF recurrence. Multivariate Cox regression analysis identified LAD as an independent factor affecting AF recurrence in patients with a high predictive efficiency. Kaplan-Meier survival analysis showed that increased LAD (>4.5 cm) was associated with postoperative AF recurrence. Therefore, LAD has better predictive power and can be an indicator for predicting postoperative AF recurrence.

Paired Remote Ischemic Preconditioning in Recipients and Living Donors Can Mitigate Cardiovascular Stress in Recipients After Living-Donor Kidney Transplantation: A Propensity-Score-Matching Analysis.

Background and Objectives: This study explored the effect of paired remote ischemic preconditioning (RIPC), involving both recipients and living donors, on cardiovascular stress in recipients after living-donor kidney transplantation (LDKT). The analysis included an assessment of the impact on cardiovascular biomarkers and post-transplant cardiovascular clinical events. Materials and Methods: A retrospective observational cohort study of 520 adult LDKT patients was conducted, employing propensity score matching (PSM) to analyze perioperative factors. The patients were allocated to no-RIPC (n = 260) and paired-RIPC (n = 260) groups. The two groups were compared with respect to high-sensitivity troponin I (hsTnI) and B-type natriuretic peptide (BNP) levels, corrected QT (QTc) intervals, the occurrence of arrhythmia, and the requirement for cardiovascular interventions. Results: After PSM, there were no significant differences in perioperative parameters between the no-RIPC and paired-RIPC groups. However, on postoperative day (POD) 1, higher hsTnI levels and QTc interval prolongation, as well as higher incidences of arrhythmia and the need for percutaneous coronary intervention (PCI), were determined in the no-RIPC group than in the paired-RIPC group. The associations between paired RIPC and improved cardiovascular outcomes were significant, including reduced odds of elevated hsTnI levels, QTc prolongation, and arrhythmia. The no-RIPC group also had longer intensive care unit (ICU) stays, and higher rates of rescue dialysis. Conclusions: Paired-RIPC involving recipients and donors effectively reduces cardiovascular stress markers and improves postoperative cardiovascular outcomes in LDKT recipients, underscoring its potential as a protective strategy against perioperative cardiovascular risks.

Amphetamine Derivatives as Potent Central Nervous System Multitarget SERT/NET/H3 Agents: Synthesis and Biological Evaluation.

In this research, a variety of novel amphetamine derivatives were synthesized and assessed for their potential as multifaceted antidepressant agents. Among these compounds, compound 11b demonstrated potent inhibitory effects on both serotonin and noradrenaline transporters (SERT/NET) and high affinity for histamine H3 receptor (H3R), and displayed low affinity for off-target receptors (H1, α1) and hERG channels, which can reduce the prolongation of the QT interval. Molecular docking studies offered a rational binding model of compound 11b when it forms a complex with SERT, NET, and the histamine H3 receptor. In vivo behavioral studies, compound 11b dose-dependently reduced the immobility duration in the mouse FST and TST assays without a stimulatory effect on the locomotor activity. Furthermore, compound 11b had a favorable pharmacokinetic profile in rats. Thus, compound 11b has the potential to develop a novel class of drugs for the treatment of depression.