Risk stratification of sudden cardiac death in asymptomatic female Brugada syndrome patients: A literature review.

BACKGROUND AND OBJECTIVES: Risk stratification in Brugada syndrome remains a difficult problem. Given the male predominance of this disease and their elevated risks of arrhythmic events, affected females have received less attention. It is widely known that symptomatic patients are at increased risk of sudden cardiac death (SCD) than asymptomatic patients, while this might be true in the male population; recent studies have shown that this association might not be significant in females. Over the past few decades, numerous markers involving clinical symptoms, electrocardiographic (ECG) indices, and genetic tests have been explored, with several risk-scoring models developed so far. The objective of this study is to review the current evidence of clinical and ECG markers as well as risk scores on asymptomatic females with Brugada syndrome. FINDINGS: Gender differences in ECG markers, the yield of genetic findings, and the applicability of risk scores are highlighted. CONCLUSIONS: Various clinical, electrocardiographic, and genetic risk factors are available for assessing SCD risk amongst asymptomatic female BrS patients. However, due to the significant gender discrepancy in BrS, the SCD risk amongst females is often underestimated, and there is a lack of research on female-specific risk factors and multiparametric risk scores. Therefore, multinational studies pooling female BrS patients are needed for the development of a gender-specific risk stratification approach amongst asymptomatic BrS patients.

The use of minimal fluoroscopy for cardiac electrophysiology procedures: A meta-analysis and review of the literature.

BACKGROUND: Conventional catheter ablation involves prolonged exposure to ionizing radiation, potentially leading to detrimental health effects. Minimal fluoroscopy (MF) represents a safer alternative, which should be explored. Data on the safety and efficacy of this technique are limited. HYPOTHESIS: Our hypothesis is that MF is of equal efficacy and safety to conventional catheter ablation with the use of fluoroscopy by performing a meta-analysis of both randomized controlled trials (RCTs) and real-world registry studies. METHODS: Pubmed and Embase were searched from their inception to July 2020 for RCTs, cohort and observational studies that assessed the outcomes of catheter ablation using a MF technique versus the conventional approach. RESULTS: Fifteen studies involving 3795 patients were included in this meta-analysis. There was a significant reduction in fluoroscopy and procedural time with no difference in acute success (odds ratio [OR]:0.74, 95% CI: 0.50-1.10, p = .14), long-term success (OR:0.92, 95% CI: 0.65-1.31, p = .38), arrhythmia recurrence (OR:1.24, 95% CI: 0.75-2.06, p = .97) or rate of complications. (OR:0.83, 95% CI: 0.46-1.48, p = .65). Additionally sub-group analysis for those undergoing catheter ablation for atrial fibrillation (AF) did not demonstrate a difference in success or complication rates (OR:0.86, 95% CI: 0.30-2.42, p = .77). Multivariate meta-regression did not identify the presence of moderator variables. CONCLUSION: This updated meta-analysis demonstrated an overall reduction in procedural and fluoroscopy time for those undergoing a minimal fluoroscopic approach. There was no significant difference in either acute or chronic success rates or complications between a MF approach and conventional approach for the management of all arrhythmias including those undergoing catheter ablation for AF.

Safety and Tolerability of Subcutaneous Methotrexate in Routine Clinical Practice.

OBJECTIVE: To show the safety and efficacy of subcutaneous (SC) methotrexate (MTX) compared to oral MTX, alternative disease-modifying antirheumatic drugs (DMARDs) monotherapy, biologic monotherapy, and combinations (conventional and biologic combination groups) in routine clinical practice. METHODS: Clinical and laboratory data were retrospectively analyzed for rheumatology clinic attendances at a large Northeast England hospital trust between January 2014 and January 2018. Rates of adverse events and stop events (transaminitis [serum alanine aminotransferase level of >80 units/liter] or neutropenia [neutrophil count of <2.0 × 109 /liter]) were calculated, with adjustment for duration of DMARD exposure. RESULTS: In the present study, 8,394 patients received DMARDs, with 2,093 patients receiving oral MTX and 949 patients receiving SC MTX. The median dose was 15 mg (interquartile range [IQR] 10-20 mg) for oral MTX, and 20 mg (IQR 15-25 mg) for SC MTX (P < 0.0001). Continuation rates were higher for SC MTX therapy when adjusted for follow-up duration, with a rate ratio (RR) of 1.54 (95% confidence interval [95% CI] 1.40-1.70) (P < 0.0001). For the time period assessed, 2,382 patients experienced 4,358 adverse events, with 1,711 incidents of transaminitis and 2,647 incidents of neutropenia recorded. Significantly fewer adverse events were observed in patients who received SC MTX monotherapy versus those who received biologic and combination DMARD therapies (P < 0.01). Compared to oral MTX, SC MTX was associated with a nonsignificant trend toward lower rates of neutropenia, but only a slightly higher rate of transaminitis (RR 1.26 [95% CI 1.07-1.48]) (P = 0.006), despite significantly higher doses of MTX. CONCLUSION: Subcutaneous MTX is safe in routine clinical practice. This is the largest study yet reported on SC MTX and provides observational data that SC MTX is continued longer and better tolerated in patients compared to other therapy groups, especially oral MTX.

Association of NPAC score with survival after acute myocardial infarction.

BACKGROUND AND AIMS: Risk stratification in acute myocardial infarction (AMI) is important for guiding clinical management. Current risk scores are mostly derived from clinical trials with stringent patient selection. We aimed to establish and evaluate a composite scoring system to improve short-term mortality classification after index episodes of AMI, independent of electrocardiography (ECG) pattern, in a large real-world cohort. METHODS: Using electronic health records, patients admitted to our regional teaching hospital (derivation cohort, n = 1747) and an independent tertiary care center (validation cohort, n = 1276), with index acute myocardial infarction between January 2013 and December 2017, as confirmed by principal diagnosis and laboratory findings, were identified retrospectively. RESULTS: Univariate logistic regression was used as the primary model to identify potential contributors to mortality. Stepwise forward likelihood ratio logistic regression revealed that neutrophil-to-lymphocyte ratio, peripheral vascular disease, age, and serum creatinine (NPAC) were significant for 90-day mortality (Hosmer- Lemeshow test, p = 0.21). Each component of the NPAC score was weighted by beta-coefficients in multivariate analysis. The C-statistic of the NPAC score was 0.75, which was higher than the conventional Charlson's score (C-statistic = 0.63). Judicious application of a deep learning model to our dataset improved the accuracy of classification with a C-statistic of 0.81. CONCLUSIONS: The NPAC score comprises four items from routine laboratory parameters to basic clinical information and can facilitate early identification of cases at risk of short-term mortality following index myocardial infarction. Deep learning model can serve as a gatekeeper to facilitate clinical decision-making.

Figure Correction: Resting and Postexercise Heart Rate Detection From Fingertip and Facial Photoplethysmography Using a Smartphone Camera: A Validation Study.

[This corrects the article DOI: 10.2196/mhealth.7275.].

Electrocardiographic conduction and repolarization markers associated with sudden cardiac death: moving along the electrocardiography waveform.

The QT interval along with its heart rate corrected form (QTc) are well-established ECG markers that have been found to be associated with malignant ventricular arrhythmogenesis. However, extensive preclinical and clinical investigations over the years have allowed for novel clinical ECG markers to be generated as predictors of arrhythmogenesis and sudden cardiac death. Repolarization markers include the older QTc, QT dispersion and newer Tpeak - Tend intervals, (Tpeak - Tend) / QT ratios, T-wave alternans (TWA), microvolt TWA and T-wave area dispersion. Meanwhile, conduction markers dissecting the QRS complex, such as QRS dispersion (QRSD) and fragmented QRS, were also found to correlate conduction velocity and unidirectional block with re-entrant substrates in various cardiac conditions. Both repolarization and conduction parameters can be combined into the excitation wavelength (λ). A surrogate marker for λ is the index of Cardiac Electrophysiological Balance (iCEB: QT / QRSd). Other markers based on conduction-repolarization are [QRSD x (Tpeak-Tend) / QRSd] and [QRSD x (Tpeak-Tend) / (QRSd x QT)]. Advancement in technology permitted sophisticated electrophysiological analyses such as principal component analysis and periodic repolarization dynamics to further improve risk stratification. This was closely followed by other novel indices including ventricular ectopic QRS interval, the f99 index and EntropyXQT, which integrates mathematical and physical calculations for determining the risk markers. Though proven to be effective in limited patient cohorts, more clinical studies across different cardiac pathologies are required to confirm their validity. As such, this review seeks to encapsulate the development of old and new ECG markers along with their associated utility and shortcomings in clinical practice.

Tpeak-Tend, Tpeak-Tend/QT ratio and Tpeak-Tend dispersion for risk stratification in Brugada Syndrome: A systematic review and meta-analysis.

BACKGROUND: Brugada syndrome is an ion channelopathy that predisposes affected subjects to ventricular tachycardia/fibrillation (VT/VF), potentially leading to sudden cardiac death (SCD). Tpeak-Tend intervals, (Tpeak-Tend)/QT ratio and Tpeak-Tend dispersion have been proposed for risk stratification, but their predictive values in Brugada syndrome have been challenged recently. METHODS: A systematic review and meta-analysis was conducted to examine their values in predicting arrhythmic and mortality outcomes in Brugada Syndrome. PubMed and Embase databases were searched until 1 May 2018, identifying 29 and 57 studies. RESULTS: Nine studies involving 1740 subjects (mean age 45 years old, 80% male, mean follow-up duration was 68 ± 27 months) were included. The mean Tpeak-Tend interval was 98.9 ms (95% CI: 90.5-107.2 ms) for patients with adverse events (ventricular arrhythmias or SCD) compared to 87.7 ms (95% CI: 80.5-94.9 ms) for those without such events, with a mean difference of 11.9 ms (95% CI: 3.6-20.2 ms, P = 0.005; I 2 = 86%). Higher (Tpeak-Tend)/QT ratios (mean difference = 0.019, 95% CI: 0.003-0.036, P = 0.024; I 2 = 74%) and Tpeak-Tend dispersion (mean difference = 7.8 ms, 95% CI: 2.1-13.4 ms, P = 0.007; I 2 = 80%) were observed for the event-positive group. CONCLUSION: Tpeak-Tend interval, (Tpeak-Tend)/QT ratio and Tpeak-Tend dispersion were higher in high-risk than low-risk Brugada subjects, and thus offer incremental value for risk stratification.

Resting and Postexercise Heart Rate Detection From Fingertip and Facial Photoplethysmography Using a Smartphone Camera: A Validation Study.

BACKGROUND: Modern smartphones allow measurement of heart rate (HR) by detecting pulsatile photoplethysmographic (PPG) signals with built-in cameras from the fingertips or the face, without physical contact, by extracting subtle beat-to-beat variations of skin color. OBJECTIVE: The objective of our study was to evaluate the accuracy of HR measurements at rest and after exercise using a smartphone-based PPG detection app. METHODS: A total of 40 healthy participants (20 men; mean age 24.7, SD 5.2 years; von Luschan skin color range 14-27) underwent treadmill exercise using the Bruce protocol. We recorded simultaneous PPG signals for each participant by having them (1) facing the front camera and (2) placing their index fingertip over an iPhone's back camera. We analyzed the PPG signals from the Cardiio-Heart Rate Monitor + 7 Minute Workout (Cardiio) smartphone app for HR measurements compared with a continuous 12-lead electrocardiogram (ECG) as the reference. Recordings of 20 seconds' duration each were acquired at rest, and immediately after moderate- (50%-70% maximum HR) and vigorous- (70%-85% maximum HR) intensity exercise, and repeated successively until return to resting HR. We used Bland-Altman plots to examine agreement between ECG and PPG-estimated HR. The accuracy criterion was root mean square error (RMSE) ≤5 beats/min or ≤10%, whichever was greater, according to the American National Standards Institute/Association for the Advancement of Medical Instrumentation EC-13 standard. RESULTS: We analyzed a total of 631 fingertip and 626 facial PPG measurements. Fingertip PPG-estimated HRs were strongly correlated with resting ECG HR (r=.997, RMSE=1.03 beats/min or 1.40%), postmoderate-intensity exercise (r=.994, RMSE=2.15 beats/min or 2.53%), and postvigorous-intensity exercise HR (r=.995, RMSE=2.01 beats/min or 1.93%). The correlation of facial PPG-estimated HR was stronger with resting ECG HR (r=.997, RMSE=1.02 beats/min or 1.44%) than with postmoderate-intensity exercise (r=.982, RMSE=3.68 beats/min or 4.11%) or with postvigorous-intensity exercise (r=.980, RMSE=3.84 beats/min or 3.73%). Bland-Altman plots showed better agreement between ECG and fingertip PPG-estimated HR than between ECG and facial PPG-estimated HR. CONCLUSIONS: We found that HR detection by the Cardiio smartphone app was accurate at rest and after moderate- and vigorous-intensity exercise in a healthy young adult sample. Contact-free facial PPG detection is more convenient but is less accurate than finger PPG due to body motion after exercise.