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Background: Fabry disease is characterized by the accumulation of globotriaosylceramide. Substrate accumulation in lysosomes is thought to trigger an inflammatory response and is responsible for progressive organ damage through the induction of autoimmunity. The levels of pteridine and kynurenine pathway metabolites increase when immune activation is observed and are employed to monitor several diseases and determine prognosis. Aims: To elucidate the effects of immune activation on the pathophysiology of Fabry disease and to investigate the potential utility of pteridine and kynurenine metabolites. Study Design: A prospective case-control study. Methods: In this study, 33 patients with Fabry disease and 33 ageand sex-matched healthy controls were included. Blood pteridine and kynurenine metabolites were studied in both groups. Organ involvement in Fabry disease and its correlation with the pteridine and kynurenine pathways were also investigated. Results: The patients' neopterin and biopterin levels and the tryptophan/ kynurenine ratio were statistically higher than those of the healthy control group (p < 0.05). A statistically significant association was found between neopterin levels and hypertrophic cardiomyopathy, cardiac arrhythmias, and GFR values (p = 0.044, p = 0.021, and p = 0.030, respectively), tryptophan and corneal verticillate, hearing loss and tinnitus (p = 0.010, p = 0.009 and p = 0.046, respectively), and kynurenine levels and valvular heart disease (p = 0.020). Conclusion: From the onset of the disease, patients with Fabry disease exhibited elevated levels of inflammation and immune activation. Furthermore, inflammation and immune activation markers can be used as early disease biomarkers. [ABSTRACT FROM AUTHOR]

Background: A previous study on mechanical complications after central venous catheterisation demonstrated differences in complication rates between male and female operators. The objective of this subgroup analysis was to further investigate these differences. The hypothesis was that differences in distribution of predefined variables between operator genders could be identified. Methods: This was a subgroup analysis of a prospective, multicentre, observational cohort study conducted between March 2019 and December 2020 including 8 586 patients ≥ 16 years receiving central venous catheters at four emergency care hospitals. The main outcome measure was major mechanical complications defined as major bleeding, severe cardiac arrhythmia, pneumothorax, arterial catheterisation, and persistent nerve injury. Independent t-test and χ2 test were used to investigate differences in distribution of major mechanical complications and predefined variables between male and female operators. Multivariable logistic regression analysis was used to determine association between operator gender and major mechanical complications. Results: Female operators had a lower rate of major mechanical complications than male operators (0.4% vs 0.8%, P =.02), were less experienced (P <.001), had more patients with invasive positive pressure ventilation (P <.001), more often chose the internal jugular vein (P <.001) and more frequently used ultrasound guidance (P <.001). Male operators more often chose the subclavian vein (P <.001) and inserted more catheters with bore size ≥ 9 Fr (P <.001). Multivariable logistic regression analysis showed that male operator gender was associated with major mechanical complication (OR 2.67 [95% CI: 1.26–5.64]) after correction for other relevant independent variables. Conclusions: The hypothesis was confirmed as differences in distribution of predefined variables between operator genders were found. Despite being less experienced, female operators had a lower rate of major mechanical complications. Furthermore, male operator gender was independently associated with a higher risk of major mechanical complications. Future studies are needed to further investigate differences in risk behaviour between male and female operators. Trial registration: Clinicaltrials.gov identifier: NCT03782324. Date of registration: 20/12/2018. [ABSTRACT FROM AUTHOR]

Introduction: Opioid withdrawal is one of the most critical complications of opioid use disorder. In this study, we aimed to examine the possible risk of ventricular arrhythmia and sudden cardiac death by calculating electrocardiography (ECG) changes, the markers of ventricular repolarization, in opioid withdrawal. Methods: A total of 90 patients diagnosed with opioid withdrawal who met the inclusion and exclusion criteria were included in the study. QT, QTc, TPe/QT, and TPe/QTc ratios of patients with a Clinical Opiate Withdrawal Scale (COWS) score higher than five and a Framingham heart risk score lower than 10% were measured in 12-lead ECG. Results: A significant difference was found between the patients' heart rate, QT, QTc, and TPe/QT values during withdrawal (entry-first) and after withdrawal (second) (p<0.05). Mean QT First Value (380.69±22.46) was significantly different and higher than Mean QT Second Value (372.82±19.998); Mean QTc First Value (435.41±16.22) was significantly different and higher than Mean QTc Second Value (418.03±17.79); Mean Tpe First Value (81.62±6.009) was significantly different and higher than Mean Tpe Second Value (79.93±5.524); and The Mean Tpe/QT First Value (0.221±0.005) was significantly different and higher than the Mean Tpe/ QT Second Value (0.213±0.004) (p<0.05). Conclusion: The findings of our study show that electrocardiographic QT, QTc, Tpe and Tpe/QTc values, which indicate the risk of sudden cardiac death and ventricular arrhythmia, are significantly higher during opioid withdrawal. In addition to the regulation of addiction treatment during opioid withdrawal, it should be considered that individuals may be at cardiac risk, and the patient should be monitored for cardiac arrhythmia during the withdrawal period. [ABSTRACT FROM AUTHOR]

Background: The hospital-at-home (HAH) model is a viable alternative for conventional in-hospital stays worldwide. Serum electrolyte abnormalities are common in acute patients, especially in those with many comorbidities. Pathologic changes in cardiac electrophysiology pose a potential risk during HAH stays. Periodical electrocardiogram (ECG) tracing is therefore advised, but few studies have evaluated the accuracy and efficiency of compact, self-activated ECG devices in HAH settings. This study aimed to evaluate the reliability of such a device in comparison with a standard 12-lead ECG. Methods: We prospectively recruited consecutive patients admitted to the Sheba Beyond Virtual Hospital, in the HAH department, during a 3-month duration. Each patient underwent a 12-lead ECG recording using the legacy device and a consecutive recording by a compact six-lead device. Baseline patient characteristics during hospitalization were collected. The level of agreement between devices was measured by Cohen's kappa coefficient for inter-rater reliability (Ϗ). Results: Fifty patients were included in the study (median age 80 years, IQR 14). In total, 26 (52%) had electrolyte disturbances. Abnormal D-dimer values were observed in 33 (66%) patients, and 12 (24%) patients had elevated troponin values. We found a level of 94.5% raw agreement between devices with regards to nine of the options included in the automatic read-out of the legacy device. The calculated Ϗ was 0.72, classified as a substantial consensus. The rate of raw consensus regarding the ECG intervals' measurement (PR, RR, and QT) was 78.5%, and the calculated Ϗ was 0.42, corresponding to a moderate level of agreement. Conclusion: This is the first report to our knowledge regarding the feasibility of using a compact, six-lead ECG device in the setting of an HAH to be safe and bearing satisfying agreement level with a legacy, 12-lead ECG device, enabling quick, accessible arrythmia detection in this setting. Our findings bear a promise to the future development of telemedicine-based hospital-at-home methodology. [ABSTRACT FROM AUTHOR]

Aim: This study was conducted to examine the electrocardiographic markers used in the risk assessment of cardiac arrhythmia in children with obesity. Materials and Methods: In this prospective study, 60 children aged 3-17 years with exogenous obesity and 60 age and sex-matched healthy controls were included. Demographic data, assessment of atrial and ventricular arrhythmia risk markers in electrocardiography, and standard echocardiography measurements were performed. Values of p<0.05 were considered significant. Results: The mean ages of the study and control groups were 11.51±3.48 years and 10.74±3.72 years, respectively. Both groups had 30 males and 30 females. The study group had significantly higher average mean body mass index (BMI) compared to the control group. In electrocardiographic examinations, P-wave dispersion, QT dispersion (QTd), corrected QTd (QTcd), Tpeak-Tend (Tp-e), Tp-e/QT, and Tp-e/QTc values were significantly higher in the obese group compared to the control group. In echocardiographic examinations, the dimensions of the heart chambers and vascular structure and wall thicknesses were found to be significantly higher in those children with obesity. Conclusion: The electrocardiographic risk markers used to predict cardiac arrhythmias were found to be increased in those children with obesity. This may suggest that increased body weight and adiposity may have unfavorable effects on the cardiac conduction system. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy is the mainstay treatment for most solid tumours. However, its cardiotoxicity is not yet known and studied, and its uncertainty is even greater in elderly patients. For this reason, this ambispective study was conducted in 195 patients over 70 years of age who were treated with immunotherapy. The percentage of patients with cardiotoxicity was 1.54%; 1.35% of patients with previous heart disease were diagnosed with cardiotoxicity, and 1.65% of those without previous heart disease were diagnosed with cardiotoxicity. The median time from the initiation of treatment until the cardiac event was 45 days. The most frequent toxicity was myocarditis, which was identified in 66.7% of patients, followed by arrhythmias in 33.3% of patients. In conclusion, immunotherapy is shown to be a safe treatment in elderly cancer patients in terms of cardiotoxicity. Introduction: Immunotherapy represents a key pillar of cancer treatments, with high response rates and long survival. Its use is increasing, mainly at the expense of the geriatric population due to the ageing of this population. However, despite its benefit, its safety in certain areas such as cardiotoxicity is largely unknown. The aim of this study is to assess the safety of immunotherapy in elderly patients using real-world data. Methods: This is an ambispective study of patients ≥ 70 years old with solid tumours who were treated with immunotherapy at the University Hospital of Salamanca. Cardiotoxicity was assessed using the CTCAEv5.0 criteria. Results: In total, 195 patients were included (76.9% male and 23.1% female), with a mean age of 75 years [70–93]. The percentage of patients with cardiotoxicity was 1.54%; 1.35% of patients with previous heart disease were diagnosed with cardiotoxicity, and 1.65% of those without previous heart disease were diagnosed with cardiotoxicity. The median time from the initiation of treatment until the cardiac event was 45 days [14–96]. The most frequent toxicity was myocarditis in 66.7% of patients, followed by arrhythmias in 33.3% of patients. Conclusions: Immunotherapy is shown to be a safe treatment in elderly cancer patients in terms of cardiotoxicity. The event rate shows no difference between patients with or without cardiac comorbidity. [ABSTRACT FROM AUTHOR]

Objective: Ventricular extrasystole is one of the most common rhythm disorders in children, and almost all of them are characterized by normal cardiac functions without structural cardiac abnormalities. The aim of this study was to assess the clinical course of ventricular extrasystole in children who did not have cardiac structural abnormalities. Materials and Methods: This retrospective study analyzed 24-hour rhythm Holter recordings performed in our clinic in children. Patients diagnosed with isolated ventricular extrasystole in Holter records and without structural heart disease on echocardiography were included in the evaluation. Results: A total of 20 160 Holter results were evaluated in the study, and 226 patients (male; 66%) met the criteria. The mean follow-up time was 8.7 ± 3.2 years. While 81.8% of the patients were asymptomatic, the most common symptom was palpitation and 5 patients had syncope. Of the patients, 72 (31.8%) received medical therapy. Beta-blockers were the most often prescribed medication. Cardiomyopathy did not develop in any of the patients during the followup period. A partial reduction in the frequency of ventricular extrasystole was observed in 42% of the patients, while complete recovery was observed in 22%. Conclusion: Ventricular extrasystole in children generally has a good prognosis; most of them are asymptomatic, and the rates of spontaneous regression over time are quite high, regardless of the origin. [ABSTRACT FROM AUTHOR]

Purpose: To report the result of percutaneous nephrolithotripsy (PCNL) via standard nephrostomy tract in a single training institution. The perioperative complications in relation to the comorbid state are particularly assessed. Patients and methods: A prospective interventional study between January 2019 to November 2022, included 210 patients scheduled for PCNL. The average age was 40.3 ± 11.8 years (range 18- 67 years). Patients were categorized into two groups. The first group comprised 146 cases (69 .5%) with no associated co-morbidities while the second group 64 (30.5%) had co-morbidities such as obesity in 4 cases (1.9%), hypertension (HTN) in 24 cases (11.4%) cases, diabetes mellitus (DM) in 17 (8.1%) cases, history of recurrent stone surgery in 11 (5.2%) cases and more than one in 8 cases (3.8%). Co-morbidities, stone burden, location of stone, time of surgery, stay in the hospital, further operations, and negative events were among the reported data. Complications and the stone-free rate were the main outcome indicators. Results: Intraoperative complications were reported in 40 (18.8%) patients (18 group 1 and 22 group 2) during PCNL. Bleeding occurred in 22 (10.5%) patients (9 group 1 and 13 group 2), blood transfusions were needed in 4 (1.9%) (2 group 1 and 2 group 2), extravasation was observed in 11 patients (5.2%) (6 group 1 and 5 group 2) and cardiac arrhythmia in 3 (1.4%) (1 group 1 and 2 group 2) patients. Postoperative complications occurred in 61 patients (29%) (24 group 1 and 37 group 2) in the form of fever in 10 patients (4.8 %) (3 group 1 and 7 group 2) and prolonged leakage in 50 patients (23.8%) (21 group 1 and 29 group 2). One patient of group 2 died from postoperative sepsis. Extravasation and postoperative leakage were higher in diabetic patients than in non-diabetics. Stonefree rate was 60.5% (127 of 210). Clinically significant residual fragments (CSRFs) found in 70 cases (33.3%) (33 group 1 and 37 group 2). In 13 cases (6.2%) (5 group 1 and 8 group 2), clinically insignificant residual fragments (CIRFs) were found. In 8 (3 group 1 and 5 group 2) of the 13 cases, spontaneous stone passage was observed within 4-6 weeks of surgery. Residual stones in three cases (1 group 1 and 2 group 2) were asymptomatic and 4 mm or less, whereas stones increased in two cases of group 2. Among all factors studied, stone burden was significantly correlated to both intraoperative and postoperative complications. The occurrence of postoperative fever increased with large stone burden. Conclusions: PCNL is a therapeutic modality that is effective, feasible, and safe for a wide range of patients with concurrent medical issues. A steep curve is required to reduce intraoperative and postoperative complications. [ABSTRACT FROM AUTHOR]

Objectives: We assessed the association between hydroxychloroquine (HCQ) initiation and risk of arrhythmia among patients with incident rheumatoid arthritis (RA) or with incident systemic lupus erythematosus (SLE). Methods: All patients with incident RA or SLE and no arrhythmic events, not receiving antiarrhythmic medications, and not receiving HCQ prior to the index date of disease in British Columbia, Canada, between January 1996 and December 2014 were identified from administrative databases. We identified patients who were dispensed HCQ prescriptions (HCQ initiators) or were not dispensed HCQ prescriptions (HCQ noninitiators) during each study year; groups were matched 1:1 by propensity scores using baseline confounders on demographics, comorbidities, medications, and health care utilization. Outcomes were any new arrhythmias, atrial fibrillation, abnormal electrocardiograms, including long QT syndrome and conduction disorder, and other unspecified arrhythmias during follow‐up. We used cause‐specific Cox proportional hazards models with death as a competing event to assess the association between HCQ initiation and the outcomes. Results: We identified 11,518 propensity score–matched patients with RA or SLE in each group. Over the mean follow‐up of 8 years, there were 1,610 and 1,646 incident arrhythmias in the HCQ initiator group and the noninitiator group, respectively, with crude incidence rates of arrhythmia of 17.5 and 18.1 in 1,000 persons per year, respectively. The adjusted cause‐specific hazard ratio (cHR) for patients who received HCQ was 0.96 (95% confidence interval [95% CI] 0.89–1.03) compared with HCQ noninitiators, and the cHRs for patients who took HCQ and had arrhythmia subtypes of atrial fibrillation, abnormal electrocardiograms, and other unspecified arrhythmias were 0.93 (95% CI 0.83–1.04), 0.98 (95% CI 0.87–1.11), and 0.95 (95% CI 0.84–1.07), respectively. Conclusion: Risk of any type of arrhythmia was not increased among new users of HCQ. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the association between persistent early repolarization (ER) in healthy individuals and longterm cardiovascular events and mortality rates in a large cohort study. Methods: Demographic characteristics, medical records, 12-lead electrocardiograms (ECGs), and laboratory data were retrieved and analyzed from the Isfahan Cohort Study. The participants were followed up biannually via telephone interviews and 1 live structured interview in between until 2017. Individuals who had ER in all their ECGs were considered persistent ER cases. Study outcomes were cardiovascular events (unstable angina, myocardial infarction, stroke, and sudden cardiac death), cardiovascularrelated mortality, and all-cause mortality. The independent t test, the χ² test, the Mann-Whitney U test, and the Cox regression models were used for statistical analyses. Results: The study population consisted of 2696 subjects (50.5% female). Persistent ER was found in 203 subjects (7.5%), with a higher frequency in men (6.7% vs 0.8%; P<0.001). Cardiovascular events, cardiovascular-related mortality, and all-cause mortality occurred in 478 (17.7%), 101 (3.7%), and 241 (8.9%) individuals, respectively. After controlling for known cardiovascular risk factors, we found an association between ER and cardiovascular events (adjusted hazard ratio [95% confidence interval] =2.36 [1.19-4.68], P=0.014), cardiovascular-related mortality (4.97 [1.95-12.60], P=0.001), and all-cause mortality (2.50 [1.11-5.58], P=0.022) in women. No significant association was found between ER and any study outcomes in men. Conclusion: ER is common in young men with no apparent long-term cardiovascular risks. In women, ER is relatively rare, but it could be associated with long-term cardiovascular risks. [ABSTRACT FROM AUTHOR]

Objective: Atrial septal defect is a congenital heart disease usually diagnosed in childhood. This study aimed to evaluate the mid-term follow-up results of patients who underwent transcatheter closure of atrial septal defect by comparing the devices and methods used in the procedure and investigating the complications of this procedure in children. Materials and Methods: This study evaluated 232 patient files retrospectively. Of the 232 patients, 24 were excluded from the study due to missing files or data. Also, patients with multi-fenestrated atrial septal defect and aneurismatic septal tissue were excluded from the study. The following data were evaluated: follow-up time, patient complaints, symptoms, transthoracic echocardiography, and transesophageal echocardiography findings (if performed), the size of the defect as measured by balloon-sizing, the size of the device used in the procedure, and major and minor complications. Results: The study included 208 children who were diagnosed with atrial septal defect. The mean age of the patients was 88.0 ± 56.5 months. Of the patients, 170 (81.7%) had no complaints. The success rate of the procedure was found to be 95.7%. While device embolization was the most common major complication, arrhythmia was the most common minor complication. The complication rate was statistically different according to the device type used in the procedure. Conclusion: Transcatheter closure of atrial septal defect is a safe method for atrial septal defect closure in pediatric patients. The study found that defect diameters measured by different methods were not correlated with each other. The procedure complication rates differed according to device type. [ABSTRACT FROM AUTHOR]

Background: Sequencing Mendelian arrhythmia genes in individuals without an indication for arrhythmia genetic testing can identify carriers of pathogenic or likely pathogenic (P/LP) variants. However, the extent to which these variants are associated with clinically meaningful phenotypes before or after return of variant results is unclear. In addition, the majority of discovered variants are currently classified as variants of uncertain significance, limiting clinical actionability.Methods: The eMERGE-III study (Electronic Medical Records and Genomics Phase III) is a multicenter prospective cohort that included 21 846 participants without previous indication for cardiac genetic testing. Participants were sequenced for 109 Mendelian disease genes, including 10 linked to arrhythmia syndromes. Variant carriers were assessed with electronic health record-derived phenotypes and follow-up clinical examination. Selected variants of uncertain significance (n=50) were characterized in vitro with automated electrophysiology experiments in HEK293 cells.Results: As previously reported, 3.0% of participants had P/LP variants in the 109 genes. Herein, we report 120 participants (0.6%) with P/LP arrhythmia variants. Compared with noncarriers, arrhythmia P/LP carriers had a significantly higher burden of arrhythmia phenotypes in their electronic health records. Fifty-four participants had variant results returned. Nineteen of these 54 participants had inherited arrhythmia syndrome diagnoses (primarily long-QT syndrome), and 12 of these 19 diagnoses were made only after variant results were returned (0.05%). After in vitro functional evaluation of 50 variants of uncertain significance, we reclassified 11 variants: 3 to likely benign and 8 to P/LP.Conclusions: Genome sequencing in a large population without indication for arrhythmia genetic testing identified phenotype-positive carriers of variants in congenital arrhythmia syndrome disease genes. As the genomes of large numbers of people are sequenced, the disease risk from rare variants in arrhythmia genes can be assessed by integrating genomic screening, electronic health record phenotypes, and in vitro functional studies.Registration: URL: https://www.Clinicaltrials: gov; Unique identifier; NCT03394859. [ABSTRACT FROM AUTHOR]

Background: Recent studies have investigated dogs with presumed diet‐associated dilated cardiomyopathy (daDCM), but prospective studies of multiple breeds are needed. Hypothesis/Objectives: To evaluate baseline features and serial changes in echocardiography and cardiac biomarkers in dogs with DCM eating nontraditional diets (NTDs) or traditional diets (TDs), and in dogs with subclinical cardiac abnormalities (SCA) eating NTD. Animals: Sixty dogs with DCM (NTD, n = 51; TDs, n = 9) and 16 dogs with SCA eating NTDs. Methods: Echocardiography, electrocardiography, and measurement of taurine, cardiac troponin I, and N‐terminal pro‐B‐type natriuretic peptide were performed in dogs with DCM or SCA. Diets were changed for all dogs, taurine was supplemented in most, and echocardiography and cardiac biomarkers were reassessed (3, 6, and 9 months). Results: At enrollment, there were few differences between dogs with DCM eating NTDs or TDs; none had low plasma or whole blood taurine concentrations. Improvement in fractional shortening over time was significantly associated with previous consumption of a NTD, even after adjustment for other variables (P =.005). Median survival time for dogs with DCM was 611 days (range, 2‐940 days) for the NTD group and 161 days (range, 12‐669 days) for the TD group (P =.21). Sudden death was the most common cause of death in both diet groups. Dogs with SCA also had significant echocardiographic improvements over time. Conclusions and Clinical Importance: Dogs with DCM or SCA previously eating NTDs had small, yet significant improvements in echocardiographic parameters after diet changes. [ABSTRACT FROM AUTHOR]

Background: The PRAETORIAN trial (A Prospective, Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy) showed noninferiority of subcutaneous implantable cardioverter defibrillator (S-ICD) compared with transvenous implantable cardioverter defibrillator (TV-ICD) with regard to inappropriate shocks and complications. In contrast to TV-ICD, S-ICD cannot provide antitachycardia pacing for monomorphic ventricular tachycardia. This prespecified secondary analysis evaluates appropriate therapy and whether antitachycardia pacing reduces the number of appropriate shocks.Methods: The PRAETORIAN trial was an international, investigator-initiated randomized trial that included patients with an indication for implantable cardioverter defibrillator (ICD) therapy. Patients with previous ventricular tachycardia <170 bpm or refractory recurrent monomorphic ventricular tachycardia were excluded. In 39 centers, 849 patients were randomized to receive an S-ICD (n=426) or TV-ICD (n=423) and were followed for a median of 49.1 months. ICD programming was mandated by protocol. Appropriate ICD therapy was defined as therapy for ventricular arrhythmias. Arrhythmias were classified as discrete episodes and storm episodes (≥3 episodes within 24 hours). Analyses were performed in the modified intention-to-treat population.Results: In the S-ICD group, 86 of 426 patients received appropriate therapy, versus 78 of 423 patients in the TV-ICD group, during a median follow-up of 52 months (48-month Kaplan-Meier estimates 19.4% and 17.5%; P=0.45). In the S-ICD group, 83 patients received at least 1 shock, versus 57 patients in the TV-ICD group (48-month Kaplan-Meier estimates 19.2% and 11.5%; P=0.02). Patients in the S-ICD group had a total of 254 shocks, compared with 228 shocks in the TV-ICD group (P=0.68). First shock efficacy was 93.8% in the S-ICD group and 91.6% in the TV-ICD group (P=0.40). The first antitachycardia pacing attempt successfully terminated 46% of all monomorphic ventricular tachycardias, but accelerated the arrhythmia in 9.4%. Ten patients with S-ICD experienced 13 electrical storms, versus 18 patients with TV-ICD with 19 electrical storms. Patients with appropriate therapy had an almost 2-fold increased relative risk of electrical storms in the TV-ICD group compared with the S-ICD group (P=0.05).Conclusions: In this trial, no difference was observed in shock efficacy of S-ICD compared with TV-ICD. Although patients in the S-ICD group were more likely to receive an ICD shock, the total number of appropriate shocks was not different between the 2 groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01296022. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) may lead to acute respiratory disease; cardiovascular, gastrointestinal, and coagulation complications; and even death. One of the major complications is cardiovascular disorders, including arrhythmias, myocarditis, pericarditis, and acute coronary artery disease. The aim of this study was to evaluate the frequency of cardiovascular complications and to determine its association with the prognosis of COVID-19 patients. In a prospective analytic study, 137 hospitalized COVID-19 patients were enrolled. During hospitalization, an electrocardiogram (ECG) was performed every other day, and laboratory tests such as cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were done 0, 6, and 12 hours after admission. These tests were repeated for patients with chest pain or ECG changes. Patients were categorized into three groups (improved, complicated, and expired patients) and assessed for the rate and type of arrhythmias, cardiac complications, lab tests, and outcomes of treatments. There was no significant relationship among the three groups related to primary arrhythmia and arrhythmias during treatment. The most common arrhythmia during hospitalization and after treatment was ST-T fragment changes. There was a significant age difference between the three groups (P = 0.001). There was a significant difference among the three groups for some underlying diseases, including diabetes mellitus (P = 0.003) and hyperlipidemia (P = 0.004). In our study, different types of arrhythmias had no association with patients' outcomes but age over 60 years, diabetes mellitus, and hyperlipidemia played an important role in the prognosis of COVID-19 cases. [ABSTRACT FROM AUTHOR]

Background: Remimazolam, a novel benzodiazepine, has been reported to cause less hypotension than propofol during induction of anesthesia. Therefore, remimazolam might be a valuable option in elderly patients with severe aortic stenosis who are considered to be the most vulnerable to hemodynamic instability. We aimed to evaluate the feasibility and hemodynamic effects of remimazolam as an induction agent in elderly patients with severe aortic stenosis. Methods: This prospective, open-label, single-arm, observational pilot study was conducted in a university hospital between November 2020 and April 2021. We included 20 patients aged 65 years or older scheduled for transcatheter or surgical aortic valve replacement for severe aortic stenosis under general anesthesia. Patients were administered intravenous remimazolam infusion at 6 mg/kg/h combined with 0.25 μg/kg/min of remifentanil infusion. The primary outcome was the vasopressor dosage between the induction of anesthesia and the completion of tracheal intubation. The secondary outcomes included hemodynamic changes, bispectral index changes, and the time from the start of remimazolam infusion to loss of consciousness. We also recorded awareness during anesthesia induction and serious adverse events related to death, life-threatening events, prolonged hospitalizations, and disability due to permanent damage. Results: Twenty patients aged 84 [79–86] (median [interquartile range]) with American Society of Anesthesiologists physical status 4 were analyzed. Ephedrine 0 [0–4] mg and phenylephrine 0.1 [0–0.1] mg were administered to 14/20 patients (3 doses in 1 patient, 2 doses in 4 patients, and one dose in 9 patients). Loss of consciousness was achieved at 80 [69–86] s after the remimazolam infusion was started. The mean arterial pressure decreased gradually after loss of consciousness but recovered immediately after tracheal intubation. The bispectral index values gradually decreased and reached < 60 at 120 s after loss of consciousness. Neither awareness during induction of anesthesia nor serious adverse events, such as severe bradycardia (< 40 bpm), life-threatening arrhythmia, myocardial ischemia, or anaphylactic reactions were observed. Conclusions: Remimazolam could be used as an induction agent with timely bolus vasopressors in elderly patients with severe aortic stenosis. Trial registration: UMIN Clinical Trials Registry, identifier UMIN000042318. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of implantable cardioverter-defibrillators (ICDs) on reducing mortality has not been well studied in patients with long QT syndrome (LQTS).Objectives: This study aimed to assess the survival benefits of ICDs in the overall LQTS population and in subgroups defined by ICD indications.Methods: This study included 3,035 patients (597 with ICD) from the Rochester LQTS Registry with a QTc ≥470 milliseconds or confirmed LQTS mutation. Using multivariable Cox proportional hazards models, the risk of all-cause mortality, all-cause mortality before age 50 years, and sudden cardiac death (SCD) were estimated as functions of time-dependent ICD therapy. Indication subgroups examined included patients with: 1) nonfatal cardiac arrest; 2) syncope while on beta-blockers; and 3) a QTc ≥500 milliseconds and syncope while off beta-blockers.Results: During the 118,837 person-years of follow-up, 389 patients died (137 before age 50 years, and 116 experienced SCD). In the entire population, patients with ICDs had a lower risk of death (HR: 0.54; 95% CI: 0.34-0.86), death before age 50 years (HR: 0.29; 95% CI: 0.14-0.61), and SCD (HR: 0.22; 95% CI: 0.09-0.55) than patients without ICDs did. Patients with ICDs also had a lower risk of mortality among the 3 indication subgroups (HR: 0.14; 95% CI: 0.06-0.34; HR: 0.27; 95% CI: 0.10-0.72; and HR: 0.42; 95% CI: 0.19-0.96, respectively).Conclusions: ICD therapy was associated with a lower risk of all-cause mortality, all-cause mortality before age 50 years, and SCD in the LQTS population, as wells as with a lower risk of all-cause mortality in indication subgroups. This study provides evidence supporting ICD implantation in patients with high-risk LQTS. [ABSTRACT FROM AUTHOR]

Background: Myocardial fibrosis and left ventricular (LV) longitudinal strain are independently associated with adverse clinical outcomes. However, the relationship between tissue properties and strain indices as well as their collective impact on outcomes are yet to be fully elucidated. We aim to investigate the relationship between LV global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) with extracellular volume (ECV) and their collective impact. Methods: Consecutive patients referred for clinical cardiovascular magnetic resonance (CMR) due to cardiomyopathy were prospectively enrolled. All patients underwent CMR with T1 mapping. ECV was calculated incorporating native and post-contrast T1 as well as hematocrit. LV GLS, GCS, and GRS were assessed by feature tracking. Hazard ratios and Kaplan–Meier curves were produced to assess the association between strains and T1 mapping indices with a composite outcome of all-cause mortality and hospitalized heart failure. Results: The study consisted of 259 patients with mixed referring diagnoses of non-ischemic/ischemic cardiomyopathy and 21 normal controls. Decreased GLS, GCS and GRS were associated with increased ECV, increased native T1, and reduced post-contrast T1 in a dose dependent manner when T1 or ECV was in the abnormal range. After a mean follow-up of 31 ± 23 months, 41 events occurred including 37 heart failure admissions and 4 deaths. Kaplan–Meier plots demonstrated that reduced strains were associated with reduced event-free survival predominantly in patients with increased ECV (≥ 28.3%). The worst outcome was among those with both reduced strains and increased ECV. In the multivariable models, increased ECV, reduced post-contrast T1 and reduced strains in all 3 directions remained predictors of outcome risk, respectively. Conclusion: Our findings highlight the intrinsic link between altered CMR tissue properties and impaired myocardial mechanical performance and additionally demonstrate improved risk stratification by characterizing tissue property among patients with reduced strain. [ABSTRACT FROM AUTHOR]

Background: The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled.Objectives: The study sought to assess the prognostic impact of disease-causing genetic variants in DCM.Methods: Baseline and longitudinal clinical data from 1,005 genotyped DCM probands were retrospectively collected at 20 centers. A total of 372 (37%) patients had pathogenic or likely pathogenic variants (genotype positive) and 633 (63%) were genotype negative. The primary endpoint was a composite of major adverse cardiovascular events. Secondary endpoints were end-stage heart failure (ESHF), malignant ventricular arrhythmia (MVA), and left ventricular reverse remodeling (LVRR).Results: After a median follow-up of 4.04 years (interquartile range: 1.70-7.50 years), the primary endpoint had occurred in 118 (31.7%) patients in the genotype-positive group and in 125 (19.8%) patients in the genotype-negative group (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.17-1.94; P = 0.001). ESHF occurred in 60 (16.1%) genotype-positive patients and in 55 (8.7%) genotype-negative patients (HR: 1.67; 95% CI: 1.16-2.41; P = 0.006). MVA occurred in 73 (19.6%) genotype-positive patients and in 77 (12.2%) genotype-negative patients (HR: 1.50; 95% CI: 1.09-2.07; P = 0.013). LVRR occurred in 39.6% in the genotype-positive group and in 46.2% in the genotype-negative group (P = 0.047). Among individuals with baseline left ventricular ejection fraction ≤35%, genotype-positive patients exhibited more major adverse cardiovascular events, ESHF, and MVA than their genotype-negative peers (all P < 0.02). LVRR and clinical outcomes varied depending on the underlying affected gene.Conclusions: In this study, DCM patients with pathogenic or likely pathogenic variants had worse prognosis than genotype-negative individuals. Clinical course differed depending on the underlying affected gene. [ABSTRACT FROM AUTHOR]

Background and Aims: Atrial fibrillation frequently occurs in the postoperative period of cardiac surgery, associated with an increase in morbidity and mortality. The scores POAF, CHA2DS2-VASc and HATCH demonstrated a validated ability to predict atrial fibrillation after cardiac surgery (AFCS). The objective is to develop and validate a risk score to predict AFCS from the combination of the variables with highest predictive value of POAF, CHA2DS2-VASc and HATCH models.Methods: We conducted a single-center cohort study, performing a retrospective analysis of prospectively collected data. The study included consecutive patients undergoing cardiac surgery in 2010-2016. The primary outcome was the development of new-onset AFCS. The variables of the POAF, CHA2DS2-VASc and HATCH scores were evaluated in a multivariate regression model to determine the predictive impact. Those variables that were independently associated with AFCS were included in the final model.Results: A total of 3113 patients underwent cardiac surgery, of which 21% presented AFCS. The variables included in the new score COM-AF were: age (≥75: 2 points, 65-74: 1 point), heart failure (2 points), female sex (1 point), hypertension (1 point), diabetes (1 point), previous stroke (2 points). For the prediction of AFCS, COM-AF presented an AUC of 0.78 (95% CI 0.76-0.80), the rest of the scores presented lower discrimination ability (P < 0.001): CHA2DS2-VASc AUC 0.76 (95% CI 0.74-0.78), POAF 0.71 (95% CI 0.69-0.73) and HATCH 0.70 (95% CI: 0, 67-0.72). Multivariable analysis demonstrated that COM-AF score was an independent predictor of AFCS: OR 1,91 (IC 95% 1,63-2,23).Conclusion: From the combination of variables with higher predictive value included in the POAF, CHA2DS2-VASc, and HATCH scores, a new risk model system called COM-AF was created to predict AFCS, presenting a greater predictive ability than the original ones. Being necessary future prospective validations. [ABSTRACT FROM AUTHOR]

Background: Cardiac implantable electronic devices (CIED) are becoming more common for the management of underlying of cardiac dysrhythmias, and more patients with these devices are presenting for cardiac and noncardiac procedures.Methods: We performed a retrospective, cohort, single-center study at a tertiary teaching medical center, gathering 151 patients with CIED undergoing elective and emergent surgeries for the time period between November 2013 and December 2016. We aimed to determine whether patients with CIED had the device interrogated before surgery as recommended by the Heart Rhythm Society (HRS)/American Society of Anesthesiologists (ASA) consensus, whether this lack of compliance led to delay in the holding area before surgery and determine the presence of intra- or postoperative cardiac events in these patients.Results: A total of 76% of patients had interrogation of the device before surgery. Emergent cases were not interrogated as much as elective cases preoperatively (43% vs. 18%, respectively; P < 0.05). In total, 6% of cases had a CIED-related average holding area delay time of 54 minutes. Patients without preoperative device interrogation had more perioperative cardiac events than those who had the device checked (25% vs. 8%, respectively; odds ratio [OR] 0.26; 95% CI, 0.09-0.7, P < 0.013).Conclusions: Our findings suggest that preoperative interrogation of the device plays a significant role to minimize the incidence of perioperative cardiac adverse events. Institutional providers show a lack of compliance with HRS/ASA recommendations for preoperative CIED management. Further research is required to determine if improved compliance to recommendations will lead to enhanced outcomes. [ABSTRACT FROM AUTHOR]

The prevalence of type 2 diabetes (T2D) is increasing worldwide, but current treatments have limitations. miRNAs may play a key role in the development of T2D and can be targets for novel therapies. Here, we examined whether T2D is associated with altered expression and DNA methylation of miRNAs using adipose tissue from 14 monozygotic twin pairs discordant for T2D. Four members each of the miR-30 and let-7-families were downregulated in adipose tissue of subjects with T2D versus control subjects, which was confirmed in an independent T2D case-control cohort. Further, DNA methylation of five CpG sites annotated to gene promoters of differentially expressed miRNAs, including miR-30a and let-7a-3, was increased in T2D versus control subjects. Luciferase experiments showed that increased DNA methylation of the miR-30a promoter reduced its transcription in vitro. Silencing of miR-30 in adipocytes resulted in reduced glucose uptake and TBC1D4 phosphorylation; downregulation of genes involved in demethylation and carbohydrate/lipid/amino acid metabolism; and upregulation of immune system genes. In conclusion, T2D is associated with differential DNA methylation and expression of miRNAs in adipose tissue. Downregulation of the miR-30 family may lead to reduced glucose uptake and altered expression of key genes associated with T2D. [ABSTRACT FROM AUTHOR]

Background: Left ventricular noncompaction (LVNC) is a heterogeneous entity with uncertain prognosis.Objectives: This study sought to develop and validate a prediction model of major adverse cardiovascular events (MACE) and to identify LVNC cases without events during long-term follow-up.Methods: This is a retrospective longitudinal multicenter cohort study of consecutive patients fulfilling LVNC criteria by echocardiography or cardiovascular magnetic resonance. MACE were defined as heart failure (HF), ventricular arrhythmias (VAs), systemic embolisms, or all-cause mortality.Results: A total of 585 patients were included (45 ± 20 years of age, 57% male). LV ejection fraction (LVEF) was 48% ± 17%, and 18% presented late gadolinium enhancement (LGE). After a median follow-up of 5.1 years, MACE occurred in 223 (38%) patients: HF in 110 (19%), VAs in 87 (15%), systemic embolisms in 18 (3%), and 34 (6%) died. LVEF was the main variable independently associated with MACE (P < 0.05). LGE was associated with HF and VAs in patients with LVEF >35% (P < 0.05). A prediction model of MACE was developed using Cox regression, composed by age, sex, electrocardiography, cardiovascular risk factors, LVEF, and family aggregation. C-index was 0.72 (95% confidence interval: 0.67-0.75) in the derivation cohort and 0.72 (95% confidence interval: 0.71-0.73) in an external validation cohort. Patients with no electrocardiogram abnormalities, LVEF ≥50%, no LGE, and negative family screening presented no MACE at follow-up.Conclusions: LVNC is associated with an increased risk of heart failure and ventricular arrhythmias. LVEF is the variable most strongly associated with MACE; however, LGE confers additional risk in patients without severe systolic dysfunction. A risk prediction model is developed and validated to guide management. [ABSTRACT FROM AUTHOR]

Objectives. To observe and analyze the long-term change of different types of arrhythmias after transcatheter closure of perimembranous ventricular septal defect (pmVSD). Methods. We retrospectively collected the data of patients who underwent pmVSD closure in our institution from March 2002 to December 2010. Results. One hundred thirty-nine patients met the inclusion criteria, of which 265 (25.5%) had early arrhythmia. They were classified into two categories: conduction abnormality (191/1039; 18.4%) and origin abnormality (94/1039; 9.0%), including 20 patients with both types of arrhythmias. The median follow-up time was 84.5 months, and 103 patients (103/191; 53.9%) with early conduction block got permanent arrhythmias, while only three patients (3/94; 3.2%) with early anomalous origin arrhythmias still had an abnormal electrocardiogram. Serious arrhythmias (28/1039; 2.7%), including II° atrioventricular block (AVB), III° AVB, and complete left bundle branch block (CLBBB), can appear immediately in the early postoperative period (21 patients) or in the late outset (seven patients) after several months or even years (6 months to 8.3 years). Twenty patients (20/21; 95.2%) with serious arrhythmia in the early postoperative period improved after early treatment, but six patients relapsed or worsened during follow-up. At the endpoint, severe arrhythmia persisted in 13 patients, of which four patients got permanent pacemaker implanted, and one patient with recurrent CLBBB died from heart failure. Conclusions. The probability of delayed CAVB or bundle branch block after VSD closure is low but often occurs several years after surgery. Therefore, long-term ECG follow-up should last for several years or even decades. Serious arrhythmias that appear early after transcatheter pmVSD closure may impose a risk of recurrence although they have been cured already. Close attention should be paid to the changes of cardiac function in patients with CLBBB after VSD closure, and the severity of such arrhythmia should be taken seriously and reexamined. [ABSTRACT FROM AUTHOR]

Background: There are conflicting data on the impact of implantable cardioverter-defibrillator (ICD) shocks on subsequent mortality.Objectives: The aim of this study was to determine whether the arrhythmic substrate leading to ICD therapy or the therapy itself increases mortality.Methods: The study cohort included 5,516 ICD recipients who were enrolled in 5 landmark ICD trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, RAID). The authors evaluated the association of device therapy with subsequent mortality in 4 separate time-dependent models: model I, type of ICD therapy; model II, type of arrhythmia for which ICD therapy was delivered; model III, combined assessment of all arrhythmia and therapy types during follow-up; and model IV, incremental risk associated with repeated ICD shocks.Results: When analyzed by the type of ICD therapy (model I), a first appropriate ICD shock was associated with increased risk of subsequent mortality with or without concomitant occurrence of inappropriate shock during follow-up (hazard ratio [HR]: 2.78 and 2.31; p < 0.001 and p = 0.12), whereas inappropriate shock alone was not associated with mortality risk (HR: 1.23; p = 0.42). Similarly, ICD therapy for ventricular tachycardia (VT) ≥200 beats/min or ventricular fibrillation (VF) (model II) was associated with increased risk of death with or without concomitant therapy for VT <200 beats/min (HRs: 2.25 and 2.62; both p < 0.001), whereas appropriate therapy for VT <200 beats/min or inappropriate therapy (regardless of etiology) did not reach statistical significance (all p > 0.10). Combined assessment of all therapy and arrhythmia types during follow-up (model III) showed that appropriate ICD shocks for VF, shocks for fast VT (≥200 beats/min) without prior antitachycardia pacing (ATP), as well as shocks for fast VT delivered after failed ATP, were associated with the highest risk of subsequent death (HR: all >2.8; p < 0.001). Finally, 2 or more ICD appropriate shocks were not associated with incremental risk to the first appropriate ICD shock (model IV).Conclusion: The combined data from 5 landmark ICD trials suggest that the underlying arrhythmic substrate rather than the ICD therapy is the more important determinant of mortality in ICD recipients. [ABSTRACT FROM AUTHOR]

Background: The subcutaneous (S) implantable cardioverter-defibrillator (ICD) is safe and effective for sudden cardiac death prevention. However, patients in previous S-ICD studies had fewer comorbidities, had less left ventricular dysfunction, and received more inappropriate shocks (IAS) than in typical transvenous ICD trials. The UNTOUCHED trial (Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction) was designed to evaluate the IAS rate in a more typical, contemporary ICD patient population implanted with the S-ICD using standardized programming and enhanced discrimination algorithms.Methods: Primary prevention patients with left ventricular ejection fraction ≤35% and no pacing indications were included. Generation 2 or 3 S-ICD devices were implanted and programmed with rate-based therapy delivery for rates ≥250 beats per minute and morphology discrimination for rates ≥200 and <250 beats per minute. Patients were followed for 18 months. The primary end point was the IAS-free rate compared with a 91.6% performance goal, derived from the results for the ICD-only patients in the MADIT-RIT study (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy). Kaplan-Meier analyses were performed to evaluate event-free rates for IAS, all-cause shock, and complications. Multivariable proportional hazard analysis was performed to determine predictors of end points.Results: S-ICD implant was attempted in 1116 patients, and 1111 patients were included in postimplant follow-up analysis. The cohort had a mean age of 55.8±12.4 years, 25.6% were women, 23.4% were Black, 53.5% had ischemic heart disease, 87.7% had symptomatic heart failure, and the mean left ventricular ejection fraction was 26.4±5.8%. Eighteen-month freedom from IAS was 95.9% (lower confidence limit, 94.8%). Predictors of reduced incidence of IAS were implanting the most recent generation of device, using the 3-incision technique, no history of atrial fibrillation, and ischemic cause. The 18-month all-cause shock-free rate was 90.6% (lower confidence limit, 89.0%), meeting the prespecified performance goal of 85.8%. Conversion success rate for appropriate, discrete episodes was 98.4%. Complication-free rate at 18 months was 92.7%.Conclusions: This study demonstrates high efficacy and safety with contemporary S-ICD devices and programming despite the relatively high incidence of comorbidities in comparison with earlier S-ICD trials. The inappropriate shock rate (3.1% at 1 year) is the lowest reported for the S-ICD and lower than many transvenous ICD studies using contemporary programming to reduce IAS. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02433379. [ABSTRACT FROM AUTHOR]

Background: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the implantable cardioverter defibrillator (ICD) in this patient population remain scarce.Methods: A Nationwide French Registry including all patients with tetralogy of Fallot with an ICD was initiated in 2010 by the French Institute of Health and Medical Research. The primary time to event end point was the time from ICD implantation to first appropriate ICD therapy. Secondary outcomes included ICD-related complications, heart transplantation, and death. Clinical events were centrally adjudicated by a blinded committee.Results: A total of 165 patients (mean age, 42.2±13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (interquartile range) follow-up of 6.8 (2.5-11.4) years, 78 (47.3%) patients received at least 1 appropriate ICD therapy. The annual incidence of the primary outcome was 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively; P=0.03). Overall, 71 (43.0%) patients presented with at least 1 ICD complication, including inappropriate shocks in 42 (25.5%) patients and lead dysfunction in 36 (21.8%) patients. Among 61 (37.0%) patients in primary prevention, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with, respectively, 0, 1, 2, or ≥3 guidelines-recommended risk factors. QRS fragmentation was the only independent predictor of appropriate ICD therapies (hazard ratio, 3.47 [95% CI, 1.19-10.11]), and its integration in a model with current criteria increased the 5-year time-dependent area under the curve from 0.68 to 0.81 (P=0.006). Patients with congestive heart failure or reduced left ventricular ejection fraction had a higher risk of nonarrhythmic death or heart transplantation (hazard ratio, 11.01 [95% CI, 2.96-40.95]).Conclusions: Patients with tetralogy of Fallot and an ICD experience high rates of appropriate therapies, including those implanted in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria including QRS fragmentation might improve risk stratification. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03837574. [ABSTRACT FROM AUTHOR]

Background: Little is known about the risk stratification of patients with myocarditis undergoing ventricular tachycardia (VT) ablation.Objectives: This study sought to describe VT ablation results and identify factors associated with arrhythmia recurrences in a cohort of patients with myocarditis.Methods: The authors enrolled 125 consecutive patients with myocarditis, undergoing VT ablation. Before ablation, disease stage was evaluated, to identify active (AM) versus previous myocarditis (PM). The primary study endpoint was assessment of VT recurrences by 12-month follow-up. Predictors of VT recurrences were retrospectively identified.Results: All patients (age 51 ± 14 years, 91% men, left ventricular ejection fraction 52% ± 9%) had history of myocarditis diagnosed by endomyocardial biopsy (59%) and/or cardiac magnetic resonance (90%). Furthermore, all had multiple episodes of drug-refractory VTs. Multimodal pre-procedural staging identified 47 patients with AM (38%) and 78 patients with PM (62%). All patients showed low-voltage areas (LVA) at electroanatomical map (97% epicardial or endoepicardial); of them, 25 (20%) had wide borderzone (WBZ, constituting >50% of the whole LVA). VT recurrences were documented in 25 patients (20%) by 12 months, and in 43 (34%) by last follow-up (median 63 months; interquartile range: 39 to 87). At multivariable analysis, AM stage was the only predictor of VT recurrences by 12 months (hazard ratio: 9.5; 95% confidence interval: 2.6 to 35.3; p < 0.001), whereas both AM stage and WBZ were associated with arrhythmia recurrences anytime during follow-up. No VT episodes were found after redo ablation was performed in 23 patients during PM stage.Conclusion: Our findings suggest that VT ablation should be avoided during AM, but is often of benefit for recurrent VT after the acute phase of myocarditis. [ABSTRACT FROM AUTHOR]

Introduction: Atrial Fibrillation (AF) is the most common arrhythmia in clinical practice and imposes a great burden on health care resources. There is limited data regarding the impact of AF in our population. Aim: To estimate the mortality and Major adverse Cardiovascular events {(MACE)- Acute Coronary Syndrome (ACS), Stroke, Cardiac death} in AF patients in a tertiary care centre in South India. Materials and Methods: This prospective cohort study included all patients >18 years with newly diagnosed or previously documented evidence of AF in ECG. Transient reversible causes and critically ill patients were excluded. Total of 346 patients were recruited and prospectively, followed-up at 1, 3, 6 and 12 months for development of MACE, anticoagulation status, Prothrombin Time (PT), International Normalised Ratio (INR) and major bleeding events. Baseline data including clinical parameters, comorbidities and appropriate investigations such as Electrocardiography (ECG) and Echocardiogram (ECHO) parameters were collected with a structured questionnaire and analysed at one year using appropriate statistical tests. Results: Average age was 60.5 years (SD 11.5 years) and majority (74.6%) were between 50-75 years. Females were more (59.5% vs 40.5%). Most common AF risk factor was Hypertension (44.5%) followed by Rheumatic Heart Disease (RHD) in 27.2% of AF patients. AF was classified as permanent in 42.2%, persistent in 23.1% and paroxysmal in 34.7%. Valvular AF was present in 26.6% and non-valvular AF in 73.4%. At one year, 17 patients were lost to follow-up. CHA2DS2VASc score of ≥2 was present in 65.1%. During one year follow-up the MACE rate was 26.7% (ischemic stroke in 9.4%, ACS in 2.7% and cardiac mortality in 14.6 %). Mean time in Therapeutic Range (TTR) was 28.12%. TTR >60% (good control) was present in only 9.2%. Conclusion: AF continues to be a significant arrhythmia causing substantial morbidity and mortality. Non-valvular AF was thrice as common as valvular AF. Though 3/4th of the patients were on oral anticoagulants, <10% had their INR under good control which contributed to the higher events. To improve the outcomes in AF patients, treatment of risk factors and optimal anticoagulation plays a crucial role. [ABSTRACT FROM AUTHOR]

Background: In the few studies of clinical experience available, cigarette smoking may be associated with ischemic heart disease and acute coronary events, which can be reflected in the electrocardiogram (ECG). However, there is no formal proof of a significant relationship between cigarette smoking and electrocardiogram results. In this study, we therefore investigate and prove the relationship between electrocardiogram and smoking using unsupervised neural network techniques.Methods: In this research, a combination of two techniques of pattern recognition; feature extraction and clustering neural networks, is specifically investigated during the diagnostic classification of cigarette smoking based on different electrocardiogram feature extraction methods, such as the reduced binary pattern (RBP) and Wavelet features. In this diagnostic system, several neural network models have been obtained from the different training subsets by clustering analysis. Unsupervised neural network of clustering cigarette smoking was then implemented based on the self-organizing map (SOM) with the best performance.Results: Two ECG datasets were investigated and analysed in this prospective study. One is the public PTB diagnostic ECG databset with 290 samples (age 17-87, mean 57.2; 209 men and 81 women; 73 smoking and 133 non-smoking). The other ECG database is from Taichung Veterans General Hospital (TVGH) and includes 480 samples (240 smoking, and 240 non-smoking). The diagnostic accuracy regarding smoking and non-smoking in the PTB dataset reaches 80.58% based on the RBP feature, and 75.63% in the second dataset based on Wavelet feature.Conclusions: The electrocardiogram diagnostic system performs satisfactorily in the cigarette smoking habit analysis task, and demonstrates that cigarette smoking is significantly associated with the electrocardiogram. [ABSTRACT FROM AUTHOR]

Background: Clinical trials have shown the cardiovascular protective effect of sodium–glucose cotransporter-2 (SGLT2) inhibitors and reduced hospitalization for heart failure. However, no study has investigated the association between SGLT2 inhibitors and the risk of arrhythmias. This study aimed to evaluate the risk of new-onset arrhythmias (NOA) and all-cause mortality with the use of SGLT2 inhibitors. Methods: This was a population-based cohort study utilizing Taiwan's National Health Insurance Research Database. Each patient aged 20 years and older who took SGLT2 inhibitors was assigned to the SGLT2 inhibitor group, whereas sex-, age-, diabetes mellitus duration-, drug index date-, and propensity score-matched randomly selected patients without SGLT2 inhibitors were assigned to the non-SGLT2 inhibitor group. The study outcome was all-cause mortality and NOA. Results: A total of 399,810 patients newly diagnosed with type 2 DM were enrolled. A 1:1 matching propensity method was used to match 79,150 patients to 79,150 controls in the non-SGLT2 inhibitors group for analysis. The SGLT2 inhibitor group was associated with a lower risk of all-cause mortality [adjusted hazard ratio (aHR) 0.547; 95% confidence interval (CI) 0.482–0.621; P = 0.0001] and NOA (aHR 0.830; 95% CI 0.751–0.916; P = 0.0002). Conclusions: Patients with type 2 DM prescribed with SGLT2 inhibitors were associated with a lower risk of all-cause mortality and NOA compared with those not taking SGLT2 inhibitors in real-world practice. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to examine whether altered heart rate variability (HRV) could predict the risk of diabetes in Asians.Research Design and Methods: A cohort study was conducted in 54,075 adults without diabetes who underwent 3-min HRV measurement during health checkups between 2011 and 2014 at Kangbuk Samsung Hospital. We analyzed the time domain (SD of the normal-to-normal interval [SDNN] and root mean square differences of successive normal-to-normal intervals [RMSSD]) and the frequency domain (total power, normalized low-frequency power [LF], and normalized high-frequency power [HF] and LF/HF ratio). We compared the risk of diabetes until 2017 according to tertiles of heart rate and HRV variables, with tertile 1 serving as the reference group.Results: During 243,758.2 person-years, 1,369 subjects were diagnosed with diabetes. Both time and frequency domain variables were lower in the group with diabetes, with the exception of those with normalized LF and LF/HF ratio. In Cox analysis, as SDNN, RMSSD, and normalized HF tertiles increased, the risk of diabetes decreased (hazard ratios [95% CIs] of tertile 3: 0.81 [0.70-0.95], 0.76 [0.65-0.90], and 0.78 [0.67-0.91], respectively), whereas the risk of diabetes increased in the case of heart rate, normalized LF, and LF/HF ratio (hazard ratios [95% CIs] of tertile 3: 1.41 [1.21-1.65], 1.32 [1.13-1.53], and 1.31 [1.13-1.53), respectively) after adjusting for age, sex, BMI, smoking, drinking, systolic blood pressure, lipid level, CRP, and HOMA of insulin resistance.Conclusions: Abnormal HRV, especially decreased vagal activity and deviation in sympathovagal imbalance to sympathetic activity, might precede incident diabetes. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) can lead to cardiac complications: brady and tachyarrhythmias and sudden cardiac death. Continuous positive airway pressure (CPAP) is the gold standard for the treatment of OSA. The present study aims to demonstrate the efficiency of CPAP in the treatment of cardiac arrhythmias in patients with OSA. The study also recorded the frequency of arrhythmias in patients with untreated OSA and assessed the association between the severity of OSA and the occurrence of arrhythmias. Materials and Methods: This is a prospective cohort study. Ninety-three patients with OSA were included, aged 60 (58--64) years, with female/male sex ratio of 1:4. They were subjected simultaneously to home respiratory polygraphy examination and Holter electrocardiogram monitoring, in two different stages: at diagnosis and at the 3-month checkup after CPAP treatment. The presence of supraventricular and ventricular arrhythmias was noted. Respiratory parameter values were also recorded. Results: Statistically significant decrease in the occurrence of supraventricular (P < 0.001) and ventricular extrasystoles (P < 0.001), atrial fibrillation (AF) (P = 0.03), nonsustained ventricular tachycardia (NSVT) (P = 0.03), and sinus pauses (P < 0.001) was observed 3 months after treatment with CPAP, compared with baseline. The apnea--hypopnea index (AHI) was correlated with the ventricular extrasystoles (r = 0.273; P = 0.008). The ejection fraction of the left ventricle was inversely correlated with the episodes of NSVT (r = -0.425; P < 0.001). AF was associated with the longest apnea (r = 0.215; P = 0.04). Cardiac activity pauses were correlated with AHI (r = 0.320; P = 0.002), longest apnea (r = 0.345; P = 0.01), and oxygen desaturation index (r = 0.325; P = 0.04). Conclusion: The prevalence of cardiac arrhythmias in patients with OSA was reduced after 3 months of CPAP therapy. Cardiac arrhythmias were correlated with the severity of OSA. [ABSTRACT FROM AUTHOR]

Background: Ventricular arrhythmias (VAs) have never been systematically investigated in patients with myocarditis at different stages.Objectives: The purpose of this study was to compare baseline and follow-up characteristics of VAs in patients with active myocarditis (AM) versus previous myocarditis (PM).Methods: A total of 185 consecutive patients (69% males, age 44 ± 15 years, left ventricular ejection fraction 49 ± 14%) with myocarditis and VA at index hospitalization, including ventricular fibrillation, ventricular tachycardia (VT), nonsustained ventricular tachycardia (NSVT), and Lown's grade ≥2 premature ventricular complexes, were enrolled. AM and PM groups were defined based on endomyocardial biopsy and cardiac magnetic resonance findings. A subset of patients (n = 46, 25%) also underwent electroanatomic mapping and VA transcatheter ablation.Results: At presentation, AM patients (n = 123, 66%) more commonly had ventricular fibrillation (8 cases vs. 0 cases; p = 0.053), and both irregular (61% vs. 11%; p < 0.001) and polymorphic VA (NSVT and VT: 19% vs. 2%; p = 0.002; premature ventricular complexes: 63% vs. 16%; p < 0.001). Only in PM patients with NSVT or VT, the dominant morphology (right-bundle branch block with superior axis) was 100% predictive of abnormal LV inferoposterior substrate at both cardiac magnetic resonance and electroanatomic mapping. At 27 ± 7 months prospective follow-up, 55 patients (30%) experienced malignant VA (AM vs. PM, p = 0.385). Although a prevalence of polymorphic and irregular VA was confirmed in AM patients with persistent inflammation in follow-up (58%), a predominance of monomorphic and regular VA was found in AM patients after myocarditis healing (42%), as well as in PM patients (all p < 0.001).Conclusions: In myocarditis patients, polymorphic and irregular VA are more common during the active inflammatory phase, whereas monomorphic and regular VA are associated with healed myocarditis. [ABSTRACT FROM AUTHOR]

Background. Evidence regarding the relationship between body mass index (BMI) and 1-year unplanned readmission was limited. Therefore, the objective of this research is to investigate whether BMI was independently related to 1-year unplanned readmission in Chinese patients with acute myocardial infarction (AMI) after percutaneous transluminal coronary intervention (PCI) after adjusting for other covariates. Methods. The present study was a cohort study. A total of 214 participants with AMI after PCI were involved in a hospital in China from 1st January 2017 to 1st January 2018. The target independent variable and the dependent variable were BMI measured at baseline and 1-year unplanned readmission, respectively. Covariates involved in this study included age, gender, TC, triglyceride, HDL-C, LDL-C, PT, APTT, INR, creatinine, HGB, LVEF, discharge medication, marital status, educational level, COPD, diabetes mellitus, heart failure, history of ischemic stroke, history of hemorrhagic stroke, arrhythmia, and hypertension. Results. The average age of 172 selected participants was 60.2 ± 10.8 years old, and about 68.6% of them was male. The rate of readmission in patients with AMI was 26.14%. The result of fully adjusted binary logistic regression showed BMI was negatively associated with risk of readmission after adjusting confounders (hazard ratio (HR) = 1.1, 95% CI 0.93–1.29). Nonlinear relationship was detected between BMI and 1-year unplanned readmission, whose point was 29.3. The effect sizes and the confidence intervals of the left and right sides of inflection point were 0.9 (0.7–1.2, P for nonlinearity = 0.530) and 2.8 (1.3–5.8, P for nonlinearity = 0.008), respectively. Conclusion. BMI has a nonlinear relationship with 1-year unplanned readmission in patients with myocardial infarction. The 1-year unplanned readmission rate of overweight patients (BMI > 29.3 kg/m2) has increased significantly. Obesity paradox does not exist in terms of readmission of Chinese patients with myocardial infarction after PCI. [ABSTRACT FROM AUTHOR]

Background: Type 2 myocardial infarction (T2MI) occurs because of an acute imbalance in myocardial oxygen supply and demand in the absence of atherothrombosis. Despite being frequently encountered in clinical practice, the population-based incidence and trends remain unknown, and the long-term outcomes are incompletely characterized.Methods: We prospectively recruited residents of Olmsted County, Minnesota, who experienced an event associated with a cardiac troponin T >99th percentile of a normal reference population (≥0.01 ng/mL) between January 1, 2003, and December 31, 2012. Events were retrospectively classified into type 1 myocardial infarction (T1MI, atherothombotic event), T2MI, or myocardial injury (troponin rise not meeting criteria for myocardial infarction [MI]) using the universal definition. Outcomes were long-term all-cause and cardiovascular mortality and recurrent MI. T2MI was further subclassified by the inciting event for supply/demand mismatch.Results: A total of 5460 patients had at least one cardiac troponin T ≥0.01 ng/mL; 1365 of these patients were classified as index T1MI (age, 68.5±14.8 years; 63% male) and 1054 were classified as T2MI (age, 73.7±15.8 years; 46% male). The annual incidence of T1MI decreased markedly from 202 to 84 per 100 000 persons between 2003 and 2012 (P<0.001), whereas the incidence of T2MI declined from 130 to 78 per 100 000 persons (P=0.02). In comparison with patients with T1MI, patients with T2MI had higher long-term all-cause mortality after adjustment for age and sex, driven by early and noncardiovascular death. Rates of cardiovascular death were similar after either type of MI (hazard ratio, 0.8 [95% CI, 0.7-1.0], P=0.11). Subclassification of T2MI by cause demonstrated a more favorable prognosis when the principal provoking mechanism was arrhythmia, in comparison with postoperative status, hypotension, anemia, and hypoxia. After index T2MI, the most common MI during follow-up was a recurrent T2MI, whereas the occurrence of a new T1MI was relatively rare (estimated rates at 5 years, 9.7% and 1.7%).Conclusions: There has been an evolution in the type of MI occurring in the community over a decade, with the incidence of T2MI now being similar to T1MI. Mortality after T2MI is higher and driven by early and noncardiovascular death. The provoking mechanism of supply/demand mismatch affects long-term survival. These findings underscore the healthcare burden of T2MI and provide benchmarks for clinical trial design. [ABSTRACT FROM AUTHOR]

Objective: Patients with diabetes mellitus (DM) have elevated levels of high-sensitivity cardiac troponin (hs-cTn). We investigated the diagnostic performance of the European Society of Cardiology (ESC) algorithms to rule out or rule in acute myocardial infarction (AMI) without ST-elevation in patients with DM.Research Design and Methods: We prospectively enrolled 3,681 patients with suspected AMI and stratified those by the presence of DM. The ESC 0/1-h and 0/3-h algorithms were used to calculate negative and positive predictive values (NPV, PPV). In addition, alternative cutoffs were calculated and externally validated in 2,895 patients.Results: In total, 563 patients (15.3%) had DM, and 137 (24.3%) of these had AMI. When the ESC 0/1-h algorithm was used, the NPV was comparable in patients with and without DM (absolute difference [AD] -1.50 [95% CI -5.95, 2.96]). In contrast, the ESC 0/3-h algorithm resulted in a significantly lower NPV in patients with DM (AD -2.27 [95% CI -4.47, -0.07]). The diagnostic performance for rule-in of AMI (PPV) was comparable in both groups: 0/1-h (AD 6.59 [95% CI -19.53, 6.35]) and 0/3-h (AD 1.03 [95% CI -7.63, 9.7]). Alternative cutoffs increased the PPV in both algorithms significantly, while improvements in NPV were only subtle.Conclusions: Application of the ESC 0/1-h algorithm revealed comparable safety to rule out AMI comparing patients with and without DM, while this was not observed with the ESC 0/3-h algorithm. Although alternative cutoffs might be helpful, patients with DM remain a high-risk population in whom identification of AMI is challenging and who require careful clinical evaluation. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: To investigate the association between estimated cardiorespiratory fitness (eCRF) and risk of atrial fibrillation (AF), and examine how long-term changes in eCRF affects the AF risk. Methods: This prospective cohort study includes data of 39,844 men and women from the HUNT2 (August 15, 1995 to June 18, 1997) and the HUNT3 study (October 3, 2006 to June 25, 2008). The follow-up period was from HUNT3 until AF diagnosis or November 30, 2015. The AF diagnoses were retrieved from hospital registers and validated by medical doctors. A nonexercise test based on age, waist circumference, resting heart rate and self-reported physical activity was used to estimate CRF. Cox regression was performed to assess the association between eCRF and AF. Results: The mean age was 50.6 ± 14.6 yr for men and 50.2 ± 15.2 yr for women. Mean follow-up time was 8.1 yr. One thousand fifty-seven cases of AF were documented. For men, the highest risk reduction of AF was 31% in the fourth quintile of eCRF when compared with the first quintile (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.53–0.89). For women, the highest risk reduction was 47% in the fifth quintile when compared with the first quintile (HR, 0.53; 95% CI, 0.38–0.74). One metabolic equivalent increase in eCRF over a 10-yr period was associated with 7% lower risk of AF (HR, 0.93; 95% CI, 0.86–1.00). Participants with improved eCRF had 44% lower AF risk compared with those with decreased eCRF (HR, 0.56; 95% CI, 0.36–0.87). Conclusions: The eCRF was inversely associated with AF, and participants with improved eCRF over a 10-yr period had less risk of AF. These findings support the hypothesis that fitness may prevent AF. [ABSTRACT FROM AUTHOR]

Aims: To estimate the incidence of direct oral anticoagulant drug (DOAC) use in patients with nonvalvular atrial fibrillation and to describe user and treatment characteristics in 8 European healthcare databases representing 6 European countries. Methods: Longitudinal drug utilization study from January 2008 to December 2015. A common protocol approach was applied. Annual period incidences and direct standardisation by age and sex were performed. Dose adjustment related to change in age and by renal function as well as concomitant use of potentially interacting drugs were assessed. Results: A total of 186 405 new DOAC users (age ≥18 years) were identified. Standardized incidences varied from 1.93–2.60 and 0.11–8.71 users/10 000 (2011–2015) for dabigatran and rivaroxaban, respectively, and from 0.01–8.12 users/10 000 (2012–2015) for apixaban. In 2015, the DOAC incidence ranged from 9 to 28/10 000 inhabitants in SIDIAP (Spain) and DNR (Denmark) respectively. There were differences in population coverage among the databases. Only 1 database includes the total reference population (DNR) while others are considered a population representative sample (CPRD, BIFAP, SIDIAP, EGB, Mondriaan). They also varied in the type of drug data source (administrative, clinical). Dose adjustment ranged from 4.6% in BIFAP (Spain) to 15.6% in EGB (France). Concomitant use of interacting drugs varied between 16.4% (SIDIAP) and 70.5% (EGB). Cardiovascular comorbidities ranged from 25.4% in Mondriaan (The Netherlands) to 82.9% in AOK Nordwest (Germany). Conclusion: Overall, apixaban and rivaroxaban increased its use during the study period while dabigatran decreased. There was variability in patient characteristics such as comorbidities, potentially interacting drugs and dose adjustment. (EMA/2015/27/PH). [ABSTRACT FROM AUTHOR]

Apolipoprotein (APOE) ε4 allele has been associated with a number of age-related diseases but previous studies failed to identify any link with Frailty syndrome. The aim of the present study is to investigate the association between APOE ε4 allele and frailty syndrome. We operationalised Frailty according to the Fried definition, and we determined the APOE genotype in 1234 participants of the hellenic longitudinal investigation of ageing and diet study. Logistic regression analyses were performed to examine the association between APOE ε4 allele and frailty. Models were adjusted for age, education, sex, presence (or absence) of hypertension, diabetes, myocardial infraction, coronary disease, congestive heart failure, arrhythmia or other heart disease, family history of dementia and current smoking. The same models were performed after exclusion of patients with dementia and participants with APOE ε2/ε4 genotype. In the fully adjusted model, carriers of APOE ε4 allele had 2.753 higher odds of frailty relative to non-carriers. After trichotomization of APOE genotype, APOE ε4 heterozygotes had 2.675 higher risk of frailty compared to non-carriers while exclusion of patients with dementia or/and APOE ε2/ε4 genotype did not alter the association. The APOE ε4 allele may be a significant biomarker of frailty with diagnostic and prognostic capacity. [ABSTRACT FROM AUTHOR]

Introduction: There is scarce literature regarding the clinical course, comorbidities and long-term outcomes after myasthenic crisis (MC). The natural history of myasthenia gravis (MG) in this subset remains uncertain. Methods: The study included a cohort admitted with MC (2007–2017) in a tertiary care hospital. The comorbidities, outcomes after discharge, and prognostic factors were analyzed. Results: Sixty-two patients (89 episodes of MC) were included. Demographic data was comparable between the early- (<50 years) and late-onset (≥50 years) groups. Comorbidities included stress cardiomyopathy (14.5%), arrhythmias (6.4%), neuropathy (17.7%), pancytopenia (12.9%), encephalopathy (11.2%), neuromyotonia (4.8%), myelopathy (3.2%), and myositis (3.2%). Pulmonary embolism (P < 0.008), dysautonomia (P < 0.002), sepsis (P < 0.008), neuropathy (P < 0.002), and phrenic dysfunction (P < 0.016) were associated with prolonged ventilation. Majority of the patients (42, 67.7%) had a favorable outcome (disease status) as defined by remission/minimal manifestations at the time of last follow-up (median 36 months, IQR 15–66). Persistent bulbar weakness (P < 0.001), neuropsychiatric illness (P < 0.001), and comorbidities (P < 0.017) were associated with refractory MG. Eighteen patients (29%) had recurrent crisis. Eleven patients succumbed in the cohort. The main predictors of mortality were tumor progression (P < 0.001) and cardiac illness (P < 0.004). Discussion: A comprehensive treatment approach in MC will translate to good short- and long-term outcomes. The main cornerstones of therapy will include (1) Identification of refractory MG with the implementation of phenotype-based therapy; (2) Addressing comorbidities including cardiac autonomic neuropathy, bulbar weakness, phrenic dysfunction; and (3) Meticulous tumor surveillance. [ABSTRACT FROM AUTHOR]

Aim: To examine the longitudinal trends of cardiometabolic diseases in a large sample of adults with cerebral palsy (CP).Method: The Optum Clinformatics Data Mart is a de-identified nationwide claims database of beneficiaries from a single private payer. Beneficiaries were included if they had an International Classification of Diseases, Ninth Revision, Clinical Modification code for a diagnosis of CP. Adults with at least 3 years of continuous enrollment on a single plan between 2002 and 2009 were included in the final analyses (n=2659). We examined the longitudinal trends of incident diabetes mellitus, hypercholesterolemia, hypertension, cardiac dysrhythmias, and atherosclerosis, stratified by age categories: 18 to 39 years, 40 to 59 years, and 60 years and over. Kaplan-Meier product-limit survival curves were compared across age categories for each of the cardiometabolic outcomes, and a Cox proportional hazards regression was run to determine adjusted hazard ratios.Results: The cumulative incidence of each of the cardiometabolic diseases ranged from 6.0% for atherosclerosis to 34.4% for hypercholesterolemia at 3 years and over. Risk-adjusted Cox proportional hazard models revealed that age was a robust predictor of survival for each outcome, with higher hazard ratio ranges in middle age (hazard ratio 1.41-2.72) and older adults (hazard ratio 2.20-5.93) compared with young adults.Interpretation: Adults with CP have high rates of cardiometabolic diseases; and disease-free survival shortens significantly with higher ages.What This Paper Adds: Adults with cerebral palsy have high rates of cardiometabolic diseases. Disease-free survival of all cardiometabolic diseases shortens significantly with higher ages. The highest rates were for hypercholesterolemia and hypertension. [ABSTRACT FROM AUTHOR]

Background: The optimal duration of cardiac rhythm monitoring after emergency department (ED) presentation for syncope is poorly described. We sought to describe the incidence and time to arrhythmia occurrence to inform decisions regarding duration of monitoring based on ED risk stratification.Methods: We conducted a prospective cohort study with enrolled adult patients (≥16 years old) presenting within 24 hours of syncope at 6 EDs. We collected baseline characteristics, time of syncope and ED arrival, and the Canadian Syncope Risk Score (CSRS) risk category. We followed subjects for 30 days, and our adjudicated primary outcome was serious arrhythmic conditions (arrhythmias, interventions for arrhythmias, and unexplained death). After excluding patients with an obvious serious condition on ED presentation and those with missing CSRS predictors, we used Kaplan-Meier analysis to describe the time to serious arrhythmic outcomes.Results: A total of 5581 patients (mean age, 53.4 years; 54.5% females; 11.6% hospitalized) were available for analysis, including 346 (6.2%) for whom the 30-day follow-up was incomplete and who were censored at the last follow-up time. A total of 417 patients (7.5%) experienced serious outcomes, 207 of which (3.7%; 95% CI, 3.3%-4.2%) were arrhythmic (161 arrhythmias, 30 cardiac device implantations, 16 unexplained deaths). Overall, 4123 (73.9%) were classified as CSRS low risk, 1062 (19.0%) medium risk, and 396 (7.1%) high risk. The CSRS accurately stratified subjects as low risk (0.4% risk for 30-day arrhythmic outcome), medium risk (8.7% risk), and high risk (25.3% risk). One-half of arrhythmic outcomes were identified within 2 hours of ED arrival in low-risk patients and within 6 hours in medium- and high-risk patients, and the residual risk after these cut points were 0.2% for low-risk, 5.0% for medium-risk, and 18.1% for high-risk patients. Overall, 91.7% of arrhythmic outcomes among medium- and high-risk patients, including all ventricular arrhythmias, were identified within 15 days. None of the low-risk patients experienced ventricular arrhythmia or unexplained death, whereas 0.9% of medium-risk patients and 6.3% of high-risk patients experienced them ( P<0.0001).Conclusions: Serious underlying arrhythmia was often identified within the first 2 hours of ED arrival for CSRS low-risk patients and within 6 hours for CSRS medium- and high-risk patients. Outpatient cardiac rhythm monitoring for 15 days for selected medium-risk patients and all high-risk patients discharged from the hospital should also be considered. [ABSTRACT FROM AUTHOR]

Background: Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy, although prospective data are lacking.Methods: We conducted a prospective phase I/II trial of noninvasive cardiac radioablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs). Arrhythmogenic scar regions were targeted by combining noninvasive anatomic and electric cardiac imaging with a standard stereotactic body radiation therapy workflow followed by delivery of a single fraction of 25 Gy to the target. The primary safety end point was treatment-related serious adverse events in the first 90 days. The primary efficacy end point was any reduction in VT episodes (tracked by indwelling implantable cardioverter defibrillators) or any reduction in PVC burden (as measured by a 24-hour Holter monitor) comparing the 6 months before and after treatment (with a 6-week blanking window after treatment). Health-related quality of life was assessed using the Short Form-36 questionnaire.Results: Nineteen patients were enrolled (17 for VT, 2 for PVC cardiomyopathy). Median noninvasive ablation time was 15.3 minutes (range, 5.4-32.3). In the first 90 days, 2/19 patients (10.5%) developed a treatment-related serious adverse event. The median number of VT episodes was reduced from 119 (range, 4-292) to 3 (range, 0-31; P<0.001). Reduction was observed for both implantable cardioverter defibrillator shocks and antitachycardia pacing. VT episodes or PVC burden were reduced in 17/18 evaluable patients (94%). The frequency of VT episodes or PVC burden was reduced by 75% in 89% of patients. Overall survival was 89% at 6 months and 72% at 12 months. Use of dual antiarrhythmic medications decreased from 59% to 12% ( P=0.008). Quality of life improved in 5 of 9 Short Form-36 domains at 6 months.Conclusions: Noninvasive electrophysiology-guided cardiac radioablation is associated with markedly reduced ventricular arrhythmia burden with modest short-term risks, reduction in antiarrhythmic drug use, and improvement in quality of life.Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02919618. [ABSTRACT FROM AUTHOR]

Background: : Autonomic dysfunction (AD) is infrequently evaluated preoperatively despite having profound perioperative implications. The ANSiscope™ is a monitoring device that quantifies AD. This study aims to determine the potential of the device to predict hypotension following anesthetic induction, occurrence of arrhythmias, and inotrope requirement for patients undergoing off-pump coronary artery bypass surgery (OPCAB).Study Design: : Prospective observational double-blinded study.Materials and Methodology: Seventy-five patients undergoing OPCAB had their autonomic function assessed by ANSiscope™. They were classified into four groups based on their AD and compared to perioperative adverse events.Results: Patients with diabetes had a higher ANSindex (P = 0.0263). They had a greater decrease in systolic blood pressure (P = 0.001) and mean arterial pressure (P = 0.004) postinduction, had an increased incidence of arrhythmias (P = 0.009), required higher inotropic support immediately (P = 0.010) and at 24 h after surgery (P = 0.018), and longer duration of postoperative ventilation (P < 0.001). They also had a higher incidence of emergency conversion of OPCAB to on-pump surgery (P = 0.009).Conclusions: An increased association between AD as quantified by the ANSiscope™ and perioperative adverse outcomes was observed. An increased rate of emergency conversion of OPCAB to on-pump surgery with higher dysfunction was noted. The authors opine that the threshold for conversion must be lower in patients deemed to be at a higher risk. Proper evaluation of the autonomic nervous system empowers the anesthesiologist to anticipate and adequately prepare for complications. [ABSTRACT FROM AUTHOR]

Background: Evaluating outcome and identifying predictors of major complications among children undergoing cardiac surgery are essential to improve care. We evaluated short-term outcomes of postcardiac surgery and predictors of major complications in a national referral hospital in Indonesia. Methods: A prospective cohort study was conducted from April 2014 to March 2015 on all children undergoing cardiac surgery. Participants were followed up from the time of surgery until hospital discharge and 30-day mortality. We performed univariate and multivariate logistic regression using STATA 12-1 to identify predictors of postsurgical major complications. Results: A total of 257 patients (median age: 36 months) were recruited; 217 (84.1%) had complications, including low cardiac output syndrome (19.8%), arrhythmia (18.6%), sepsis (17.4%), and pleural effusion (14.8%). Forty-nine (19%) patients had major complications, including cardiac arrest (5%), need for emergency chest opening (3.9%), and multiple organ failure (7.4%). 12.8% died during hospital stay, and 30-day mortality was 13.6%. Predictors of major complications were cyanotic congenital heart disease (odds ratio [OR]: 4.6, 95% confidence interval [CI]: 1.5–14.2), longer duration of cardiopulmonary bypass (CPB, OR: 4.4, 95% CI: 1.5–13.4), high inotropes (OR: 13.1, 95% CI: 3.2–54.2), and increase in lactate >0.75 mmol/L/h or more in the first 24 h (OR: 37.1, 95% CI: 10.1–136.3). Conclusion: One-fifth of children undergoing cardiac surgery experienced major complications with around 13% mortality. Cyanotic congenital heart disease, longer duration of CPB, high inotropes on leaving operating theater, and increase in blood lactate are associated with major complications in children after cardiac surgery. [ABSTRACT FROM AUTHOR]

Aims: Cardiac sarcoidosis (CS) often presents with ventricular arrhythmias, heart block, and cardiomyopathy. The prognosis of CS with contemporary management is uncertain. We estimated the impact of baseline and treatment variables on left ventricular ejection fraction (LVEF), ventricular assist device placement, heart transplant, and death.Methods and Results: We identified patients with CS seen from 1994-2014 at two large academic medical centres. All met the 2014 Heart Rhythm Society expert consensus criteria for diagnosis. From the 574 patients identified, 91 met inclusion criteria. Twenty-two (24.2%) were diagnosed by endomyocardial biopsy. Cardiomyopathy was the primary presentation in 47 patients (51.6%). Within 90 days of diagnosis, 41 patients (45.0%) received prednisone alone, 29 (31.9%) received alternative immunosuppression with or without prednisone, and 21 (23.1%) received no immunosuppression. During follow-up, 31 of 47 cardiomyopathy patients experienced improvement in LVEF, while 23 experienced decline in LVEF or clinical exacerbation, and 15 of 22 patients presenting with ventricular arrhythmia had recurrence. These results did not differ by treatment group. During a median follow-up of 44 months for our cohort, 14 patients reached the composite endpoint of ventricular assist device placement, heart transplant, or death. Survival without the composite outcome did not differ by treatment group, but was worse among patients presenting with cardiomyopathy (log-rank = 0.005).Conclusion: In a large series of CS subjects, rates of ventricular arrhythmia and heart failure events remain high with no treatment regimen clearly associated with better outcome. Patients with cardiomyopathy at diagnosis were more likely to reach the composite endpoint. [ABSTRACT FROM AUTHOR]

Background: Holter monitoring (HM) is an important tool used to evaluate symptoms suspected to be caused by arrhythmias. This study was aimed at determining the diagnostic yield of Holter monitoring among symptomatic and asymptomatic patients undergoing HM at the Korle-Bu Teaching Hospital. Methods: This was a prospective study among 400 consecutive symptomatic and asymptomatic patients undergoing HM from August 2006 to December, 2009 at the Korle-Bu Teaching Hospital. Data from the Holter study were analyzed, and symptoms linked to arrhythmias were evaluated to determine the diagnostic yield of HM in symptomatic and asymptomatic patients. Results: The mean age of the patients was 51.81 ± 16 years. The most common indications (symptoms) for HM were palpitation (62.9%) and dizziness (34.0%); about half (53.3%) of the symptomatic patients had only one indication. Among the symptomatic group, 28 in 115 symptoms were linked to arrhythmias giving a diagnostic yield of 24.3% whereas in the asymptomatic group 1 in 33 of symptom was linked to arrhythmia giving a diagnostic yield of 3.0%. The study found an overall diagnostic yield of 19.6%. Conclusion: HM as a regular health check for the general population (asymptomatic cohorts) is not cost effective and does not provide significant data to influence care except when the subject is found to have symptoms. [ABSTRACT FROM AUTHOR]

Objective: Diagnosing fetal heart failure remains challenging because it is difficult to know how well the fetal myocardium will perform as loading conditions change. In adult cardiology, natriuretic peptides (NPs) are established markers of heart failure. However, the number of studies investigating NP levels in fetuses is quite limited. The aim of this study was to evaluate the significance of plasma NP levels in the assessment of heart failure in fetuses with a congenital heart defect (CHD) and/or arrhythmia.Methods: This was a prospective observational study conducted at a tertiary pediatric cardiac center. A total of 129 singletons with CHD and/or arrhythmia and 127 controls were analyzed between 2012 and 2015. Umbilical cord plasma atrial NP, brain NP and N-terminal pro-brain NP levels at birth were compared with ultrasonography findings indicating fetal heart failure, such as cardiovascular profile (CVP) score and morphological characteristics.Results: Fetuses with CHD and/or arrhythmia had higher NP levels than did controls (P < 0.01). NP levels of fetuses with CHD and/or arrhythmia were correlated inversely with CVP score (P for trend < 0.01). No differences in NP levels were found in fetuses with CHD and/or arrhythmia and a CVP score of ≥ 8 in comparison to controls. Multivariate analysis showed that a CVP score of ≤ 5, tachy- or bradyarrhythmia at birth, preterm birth and umbilical artery pH < 7.15 were associated independently with high NP levels (P < 0.01). Among fetuses with a CVP score of ≤ 7, abnormal venous Doppler sonography findings were significantly more common and more severe in fetuses with tachy- or bradyarrhythmia than in those with CHD, and those with tachy- or bradyarrhythmia had higher NP levels than did those with CHD (P = 0.01). Fetuses with right-heart defect and moderate or severe tricuspid valve regurgitation had significantly higher NP levels than did fetuses with other types of CHD (P < 0.01).Conclusions: Plasma NP levels in fetuses with CHD and/or arrhythmia are correlated with the severity of fetal heart failure. Elevated NP levels are attributed mainly to an increase in central venous pressure secondary to arrhythmia or atrioventricular valve regurgitation due to CHD, rather than to the morphological abnormality itself. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Relation between atrial fibrillation (AF) and cancer is known but not very well understood. The purpose of this prospective study was to find out whether subjects with cancer were at greater risk of AF than subjects without cancer. Materials and methods: The study was based on the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) material and had 1045 subjects and the mean follow-up time of 16.3 years. During the follow-up AF and cancer diagnosis were made (atrial flutter included) if these events were listed in the National Death Registry and/or hospital discharge registry. Results: In this study 130 subjects (12%) had cancer and 19% of these had AF, whereas only 9% of those without cancer experienced AF during the follow-up (p<0.001). Subjects in the cancer group had greater probability of developing atrial fibrillation during the follow-up time in comparison to the subjects without cancer (Hazard ratio (HR) 2.47 (95%CI) 1.57–3.88) in multivariate model including relevant confounding factors. Conclusion: The main finding of this OPERA study was that cancer is an independent risk factor of atrial fibrillation. Still it remains unclear whether this association is causative or whether cancer and atrial fibrillation just share the same pathophysiologic mechanisms. [ABSTRACT FROM AUTHOR]