Assessment of facial video-based detection of atrial fibrillation across human complexion.

Background: Early self-detection of atrial fibrillation (AF) can help delay and/or prevent significant associated complications, including embolic stroke and heart failure. We developed a facial video technology, videoplethysmography (VPG), to detect AF based on the analysis of facial pulsatile signals. Objective: The purpose of this study was to evaluate the accuracy of a video-based technology to detect AF on a smartphone and to test the performance of the technology in AF patients across the whole spectrum of skin complexion and under various recording conditions. Methods: The performance of video-based monitoring depends on a set of factors such as the angle and the distance between the camera and the patient's face, the strength of illumination, and the patient's skin tone. We conducted a clinical study involving 60 subjects with a confirmed diagnosis of AF. A continuous electrocardiogram was used as the gold standard for cardiac rhythm annotation. The VPG technology was fine-tuned on a smartphone for the first 15 subjects. Validation recordings were then done using 7053 measurements collected from the remaining 45 subjects. Results: The VPG technology detected the presence of AF using the video camera from a common smartphone with sensitivity and specificity ≥90%. The ambient level of illumination needs to be ≥100 lux for the technology to deliver consistent performance across all skin tones. Conclusion: We demonstrated that facial video-based detection of AF provides accurate outpatient cardiac monitoring including high pulse rate accuracy and medical-grade performance for AF detection.

Challenges in implementing and obtaining acceptance for J-Tpeak assessment as the clinical component of CiPA.

INTRODUCTION: This paper is based on a presentation held at the Annual Safety Pharmacology Society meeting in September 2017, at which challenges for the clinical component of CiPA were presented. FDA has published an automated algorithm for measurement of the J-Tpeak interval on a median beat from a vector magnitude lead derived from a 12-lead ECG. CiPA proposes that J-Tpeak prolongation < 10 ms can be used for drugs with a QTc effect < 20 ms to differentiate between safe and unsafe delayed repolarization and to reduce the level of ECG monitoring in late stage clinical trials. METHODS: We applied FDA's algorithm, complemented with iCOMPAS, to moxifloxacin and dolasetron data from the IQ-CSRC study with 9 subjects on active and 6 on placebo. The effect on QTcF and corrected J-Tpeak (J-Tpeak_c) was analyzed using concentration-effect modeling. RESULTS: There was a good correlation between QTcF and J-Tpeak_c prolongation after oral dosing of 400 mg moxifloxacin with placebo-adjusted, change-from-baseline (ΔΔ) J-Tpeak_c of ~12 ms at concentrations that caused ΔΔQTcF of ~20 ms. On dolasetron, J-Tpeak_c was highly variable, no prolongation was seen and an effect on ΔΔJ-Tpeak_c > 10 ms could be excluded across the observed plasma concentration range. DISCUSSION: In this limited analysis performed on the IQ-CSRC study waveforms using FDA's automated algorithm, J-Tpeak prolongation was observed on moxifloxacin, but not on dolasetron, despite clinical observations of proarrhythmias with both drugs. Challenges for the implementation of the J-Tpeak interval as a replacement or complement to the QTc interval, include to demonstrate that the proposed clinical algorithm using a J-Tpeak threshold of 10 ms, can be used to categorize drugs with a QT effect up to ~20 ms as having low pro-arrhythmic risk.

Evaluation of the ECG based Selvester scoring method to estimate myocardial scar burden and predict clinical outcome in patients with left bundle branch block, with comparison to late gadolinium enhancement CMR imaging.

BACKGROUND: Myocardial scar burden quantification is an emerging clinical parameter for risk stratification of sudden cardiac death and prediction of ventricular arrhythmias in patients with left ventricular dysfunction. We investigated the relationships among semiautomated Selvester score burden and late gadolinium enhancement-cardiovascular magnetic resonance (LGE-CMR) assessed scar burden and clinical outcome in patients with underlying heart failure, left bundle branch block (LBBB) and implantable cardioverter-defibrillator (ICD) treatment. METHODS: Selvester QRS scoring was performed on all subjects with ischemic and nonischemic dilated cardiomyopathy at Skåne University Hospital Lund (2002-2013) who had undergone LGE-CMR and 12-lead ECG with strict LBBB pre-ICD implantation. RESULTS: Sixty patients were included; 57% nonischemic dilated cardiomyopathy and 43% ischemic cardiomyopathy with mean left ventricular ejection fraction of 27.6% ± 11.7. All patients had scar by Selvester scoring. Sixty-two percent had scar by LGE-CMR (n = 37). The Spearman correlation coefficient for LGE-CMR and Selvester score derived scar was r = .35 (p = .007). In scar negative LGE-CMR, there was evidence of scar by Selvester scoring in all patients (range 3%-33%, median 15%). Fourteen patients (23%) had an event during the follow-up period; 11 (18%) deaths and six adequate therapies (10%). There was a moderate trend indicating that presence of scar increased the risk of clinical endpoints in the LGE-CMR analysis (p = .045). CONCLUSION: There is a modest correlation between LGE-CMR and Selvester scoring verified myocardial scar. CMR based scar burden is correlated to clinical outcome, but Selvester scoring is not. The Selvester scoring algorithm needs to be further refined in order to be clinically relevant and reliable for detailed scar evaluation in patients with LBBB.

A quantitative assessment of T-wave morphology in LQT1, LQT2, and healthy individuals based on Holter recording technology.

BACKGROUND: The clinical course and the precipitating risk factors in the congenital long QT syndrome (LQTS) are genotype specific. OBJECTIVES: The goal of this study was to develop a computer algorithm allowing for electrocardiogram (ECG)-based identification and differentiation of LQT1 and LQT2 carriers. METHODS: Twelve-lead ECG Holter monitor recordings were acquired in 49 LQT1 carriers, 25 LQT2 carriers, and 38 healthy subjects as controls. The cardiac beats were clustered based on heart-rate bin method. Scalar and vectorial repolarization parameters were compared for similar heart rates among study groups. The Q to Tpeak (QTpeak), the Tpeak to Tend interval, T-wave magnitude and T-loop morphology were automatically quantified using custom-made algorithms. RESULTS: QTpeak from lead II and the right slope of the T-wave were the most discriminant parameters for differentiating the 3 groups using prespecified heart rate bin (75.0 to 77.5 beats/min). The predictive model utilizing these scalar parameters was validated using the entire spectrum of heart rates. Both scalar and vectorcardiographic models provided very effective identification of tested subjects in heart rates between 60 and 100 beats/min, whereas they had limited performance during tachycardia and slightly better discrimination in bradycardia. In the 60 to 100 beats/min heart rate range, the best 2-variable model identified correctly 89% of healthy subjects, 84% of LQT1 carriers, and 92% of LQT2 carriers. A model including 3 parameters based purely on scalar ECG parameters could correctly identify 90% of the population (89% of healthy subjects, 90% of LQT1 carriers, and 92% of LQT2 carriers). CONCLUSION: Automatic algorithm quantifying T-wave morphology discriminates LQT1 and LQT2 carriers and healthy subjects with high accuracy. Such computerized ECG methodology could assist physicians evaluating subjects suspected for LQTS.

Preserved heart rate variability identifies low-risk patients with nonischemic dilated cardiomyopathy: results from the DEFINITE trial.

BACKGROUND: The recent expansion of indications for prophylactic implantable cardioverter-defibrillator (ICD) placement in subjects with nonischemic dilated cardiomyopathy has raised concerns about the cost-effectiveness of this therapy. OBJECTIVES: The purpose of this study was to identify low-risk patients with nonischemic dilated cardiomyopathy who may not require prophylactic ICD placement. METHODS: This was a prospective study of 274 participants in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, a randomized controlled trial that evaluated the role of prophylactic ICD placement in patients with nonischemic dilated cardiomyopathy. The patients underwent 24-hour Holter recording for analysis of heart rate variability (HRV). The primary HRV variable was the standard deviation of normal R-R intervals (SDNN). Patients with atrial fibrillation and frequent ventricular ectopy (>25% of beats) were excluded from HRV analysis (23% of patients). SDNN was categorized in tertiles, and Kaplan-Meier analysis was performed to compare survival in the three tertiles and excluded patients. RESULTS: The study population was 73% male, with a mean age of 59 +/- 12 years and mean left ventricular ejection fraction of 21% +/- 6%. After 3-year follow-up, significant differences in mortality rates were observed: SDNN >113 ms: 0 (0%), SDNN 81-113 ms: 5 (7%), SDNN <81 ms: 7 (10%), excluded patients: 11 (17%) (P = .03). There were no deaths in the tertile with SDNN >113 ms regardless of treatment assignment (ICD vs control). CONCLUSION: Patients with nonischemic dilated cardiomyopathy and preserved HRV have an excellent prognosis and may not benefit from prophylactic ICD placement. Patients with severely depressed HRV and patients who are excluded from HRV analysis because of atrial fibrillation and frequent ventricular ectopy have the highest mortality.

Assessment of the stability of the individual-based correction of QT interval for heart rate.

BACKGROUND: Modeling the relationship between QT intervals and previous R-R values remains a challenge of modern quantitative electrocardiography. The technique based on an individual regression model computed from a set of QT-R-R measurements is presented as a promising alternative. However, a large set of QT-R-R measurements is not always available in clinical trials and there is no study that has investigated the minimum number of QT-R-R measurements needed to obtain a reliable individual QT-R-R model. In this study, we propose guidelines to ensure appropriate use of the regression technique for heart rate correction of QT intervals. METHOD: Holter recordings from 205 healthy subjects were included in the study. QT-R-R relationships were modeled using both linear and parabolic regression techniques. Using a bootstrapping technique, we computed the stability of the individual correction models as a function of the number of measurements, the range of heart rate, and the variance of R-R values. RESULTS: The results show that the stability of QT-R-R individual models was dependent on three factors: the number of measurements included in its design, the heart-rate range used to design the model, and the T-wave amplitude. Practically our results showed that a set of 400 QT-R-R measurements with R-R values ranging from 600 to 1000 ms ensure a stable and reliable individual correction model if the amplitude of the T wave is at least 0.3 mV. Reducing the range of heart rate or the number of measurements may significantly impact the correction model. CONCLUSION: We demonstrated that a large number of QT-R-R measurements (approximately 400) is required to ensure reliable individual correction of QT intervals for heart rate.

Electrocardiographic identification of drug-induced QT prolongation: assessment by different recording and measurement methods.

BACKGROUND: Careful assessment of QT interval prolongation is required before novel drugs are approved by regulatory authorities. The choice of the most appropriate method of electrocardiogram (ECG) acquisition and QT/RR interval measurement in clinical trials requires better understanding of the differences among currently available approaches. This study compared standard and Holter-derived 12-lead ECGs for utility in detecting sotalol-induced QT/QTc and RR changes. Manual methods (digitizing pad and digital on-screen calipers) were compared for precision of QT and RR interval measurement. METHODS AND RESULTS: Sixteen hundred pairs of serial 12-lead digital ECGs were recorded simultaneously by standard resting ECG device and by continuous 12-lead digital Holter over 3 days in 39 healthy male and female volunteers. No therapy was given on the 1st day followed by 160 mg and 320 mg of sotalol on the 2nd and 3rd day, respectively. Holter-derived and standard ECGs produced nearly identical sotalol-induced QT/QTc and RR changes from baseline, as did the manual digipad and on-screen caliper measurements. The variability of on-screen QT measurement in this study was greater than that of digipad. CONCLUSIONS: Digital 12-lead Holter and standard 12-lead ECG recorders, as well as the manual digitizing pad and digital on-screen calipers, are of equal utility for the assessment of drug-induced change from baseline in QT and RR interval, although the variability of the on-screen method in this study was greater than of the digipad.