Continuous Atrial Fibrillation Monitoring From Photoplethysmography: Comparison Between Supervised Deep Learning and Heuristic Signal Processing.

BACKGROUND: Continuous monitoring for atrial fibrillation (AF) using photoplethysmography (PPG) from smartwatches or other wearables is challenging due to periods of poor signal quality during motion or suboptimal wearing. As a result, many consumer wearables sample infrequently and only analyze when the user is at rest, which limits the ability to perform continuous monitoring or to quantify AF. OBJECTIVES: This study aimed to compare 2 methods of continuous monitoring for AF in free-living patients: a well-validated signal processing (SP) heuristic and a convolutional deep neural network (DNN) trained on raw signal. METHODS: We collected 4 weeks of continuous PPG and electrocardiography signals in 204 free-living patients. Both SP and DNN models were developed and validated both on holdout patients and an external validation set. RESULTS: The results show that the SP model demonstrated receiver-operating characteristic area under the curve (AUC) of 0.972 (sensitivity 99.6%, specificity: 94.4%), which was similar to the DNN receiver-operating characteristic AUC of 0.973 (sensitivity 92.2, specificity: 95.5%); however, the DNN classified significantly more data (95% vs 62%), revealing its superior tolerance of tracings prone to motion artifact. Explainability analysis revealed that the DNN automatically suppresses motion artifacts, evaluates irregularity, and learns natural AF interbeat variability. The DNN performed better and analyzed more signal in the external validation cohort using a different population and PPG sensor (AUC, 0.994; 97% analyzed vs AUC, 0.989; 88% analyzed). CONCLUSIONS: DNNs perform at least as well as SP models, classify more data, and thus may be better for continuous PPG monitoring.

Validation of an algorithm for continuous monitoring of atrial fibrillation using a consumer smartwatch.

BACKGROUND: Consumer devices with broad reach may be useful in screening for atrial fibrillation (AF) in appropriate populations. However, currently no consumer devices are capable of continuous monitoring for AF. OBJECTIVE: The purpose of this study was to estimate the sensitivity and specificity of a smartwatch algorithm for continuous detection of AF from sinus rhythm in a free-living setting. METHODS: We studied a commercially available smartwatch with photoplethysmography (W-PPG) and electrocardiogram (W-ECG) capabilities. We validated a novel W-PPG algorithm combined with a W-ECG algorithm in a free-living setting, and compared the results to those of a 28-day continuous ECG patch (P-ECG). RESULTS: A total of 204 participants completed the free-living study, recording 81,944 hours with both P-ECG and smartwatch measurements. We found sensitivity of 87.8% (95% confidence interval [CI] 83.6%-91.0%) and specificity of 97.4% (95% CI 97.1%-97.7%) for the W-PPG algorithm (every 5-minute classification); sensitivity of 98.9% (95% CI 98.1%-99.4%) and specificity of 99.3% (95% CI 99.1%-99.5%) for the W-ECG algorithm; and sensitivity of 96.9% (95% CI 93.7%-98.5%) and specificity of 99.3% (95% CI 98.4%-99.7%) for W-PPG triggered W-ECG with a single W-ECG required for confirmation of AF. We found a very strong correlation of W-PPG in quantifying AF burden compared to P-ECG (r = 0.98). CONCLUSION: Our findings demonstrate that a novel algorithm using a commercially available smartwatch can continuously detect AF with excellent performance and that confirmation with W-ECG further enhances specificity. In addition, our W-PPG algorithm can estimate AF burden. Further research is needed to determine whether this algorithm is useful in screening for AF in select at-risk patients.

More unaffected first-degree relatives of essential tremor cases have mild cognitive deficits than age-matched controls.

BACKGROUND: In numerous case-control studies, essential tremor (ET) has been associated with cognitive impairment. ET is often familial. However, cognitive impairment has not been studied in family members of ET cases. Endophenotypes are measurable clinical characteristics that may be present in individuals with increased risk for disease; as such, they may be present before disease onset. We administered a global cognitive screen to first-degree relatives of ET cases (FD-ET) and age-matched controls (Co). METHODS: We administered the Montreal Cognitive Assessment (MoCA) to 156 FD-ET and 73 Co, none of whom were diagnosed with ET or reported tremor. MoCA <26 was considered suggestive of cognitive impairment. RESULTS: FD-ET and Co were similar with respect to age (60.1 ±â€¯8.3 vs. 60.9 ±â€¯7.4 years) and numerous demographic factors. FD-ET and Co also had similar MoCA scores; however, 34 of 156 (21.8%) FD-ET had a MoCA score <26 vs only 5 (6.9%) of 73 Co (p = 0.004). In a univariate logistic regression model, FD-ET were 3.79 times more likely to have a low (<26) MoCA than were Co (odds ratio = 3.79, p = 0.008). In a multivariate logistic regression model, adjusting for age and other covariates, FD-ET were 4.83 times more likely to have a low MoCA than were Co (odds ratio = 4.83, p = 0.003). CONCLUSION: More FD-ET had low MoCA scores when compared with Co. These data provide additional support for the scientific notions that (1) cognitive difficulties are a disease-associated feature of ET and (2) there may be a pre-tremor phase of illness in ET.

Transient, Isolated Head Tremor in "Unaffected" Individuals: Is Essential Tremor an Even More Prevalent Disease Than We Suppose?

Background: Mild and transient head tremor may sometimes be observed in otherwise tremor-free relatives of essential tremor (ET) cases, although its prevalence is unclear. A diagnostic question is whether this transient, isolated head tremor, often observed as no more than a wobble, is an early manifestation of ET or whether it is a normal finding. A direct comparison with controls is needed. Methods: Two hundred and forty-one first-degree relatives of ET cases (FD-ET) and 77 spousal controls (Co) were enrolled in a study of ET. Each underwent a detailed evaluation that included a tremor history and videotaped neurological examination. None of the enrollees reported tremor, had a prior diagnosis of ET, or had significant tremor on screening spirals. All videotaped examinations were initially reviewed by a movement disorder neurologist blinded to subject type, and among those with head tremor on examination, co-reviewed by two additional movement disorders neurologists. Results: Twenty-six (10.8, 95% Confidence interval [CI] = 7.5-15.3%) of 241 FD-ET vs. 2 (2.6, 95% CI = 0.7-9.0%) of 77 Co had isolated, transient head tremor (odds ratio = 4.54, 95% CI = 1.05-19.57, p = 0.04). No enrollee had significant upper extremity tremor and none met inclusion criteria for ET based on the presence of upper extremity tremor. With one exception, head tremor occurred during or after phonation. It was always transient (generally a single back and forth wobble) and rare (observed briefly on one or two occasions during the videotaped examination) and had a faster frequency, lower amplitude and a different quality than voluntary head shaking. Conclusion: The basis for the observed isolated head tremor is unknown, but it could be an early feature of ET in ET families.Indeed, one-in-ten otherwise unaffected first-degree relatives of ET cases exhibited such tremor. To a far lesser extent it was also observed in "unaffected" controls. In both, it is likely a sign of early, emerging, undiagnosed ET, although follow-up studies are needed to confirm this. If it were ET, it would indicate that the prevalence of ET may be considerably higher than previously suspected.

Caffeine Consumption in First-Degree Relatives of Essential Tremor Cases: Evidence of Dietary Modification Before Disease Onset.

BACKGROUND: Caffeine can exacerbate tremor. Reducing caffeine intake or switching to decaffeinated beverages can lessen tremor. Unaffected relatives of essential tremor (ET) cases often have mild, subclinical tremor. One question is whether the coffee and tea consumption pattern in these individuals differs from that of controls (Co). METHODS: We ascertained the patterns of coffee and tea intake using a structured questionnaire, and compared the use in unaffected first-degree relatives of ET cases (FD-ET) to the use in age-matched Co. Three measures of relative caffeinated coffee + tea to decaffeinated coffee + tea were constructed. Caffeine index 1 = (cups of caffeinated coffee + tea) - (cups of decaffeinated coffee + tea) consumed on the day of evaluation. Caffeine index 2 = (cups of caffeinated coffee + tea) - (cups of decaffeinated coffee + tea) consumed in a typical month. The percentage of coffee and tea that was caffeinated in a typical month was also calculated. RESULTS: There were 263 individuals (190 FD-ET, 73 Co). Caffeine index 1 in FD-ET was less than 1-half that of Co (p = 0.001). Caffeine index 2 was similarly lower in FD-ET than Co (p = 0.027). The percentage of coffee and tea that was caffeinated in a typical month was also significantly lower in FD-ET than Co (p = 0.018). CONCLUSION: The balance of caffeinated to decaffeinated beverages is different in FD-ET than Co. These data raise several intriguing questions. Among these is whether relatives of ET cases modify their caffeine consumption before disease onset.

Unaffected first-degree relatives of essential tremor cases have more imbalance than age-matched control subjects.

BACKGROUND: Endophenotypes are measurable clinical characteristics that may be present in individuals with increased risk for disease (e.g., unaffected family members). Endophenotypes are useful; they may clarify diagnosis in genetic studies and foster the development of animal models. In recent years, problems with balance and mild gait ataxia have been associated with essential tremor (ET). We compared gait and balance of first-degree relatives of ET cases (FD-ET) to that of age-matched controls (Co). METHODS: One-hundred-ninety FD-ET and 68 Co, none of whom reported tremor or were diagnosed with ET, underwent a standardized assessment of gait and balance. RESULTS: FD-ET reported more near-falls in the past year (p = 0.015) and lower balance confidence according to the Activities of Balance Confidence (ABC-6) Scale (p = 0.03). The specific ABC-6 items for which FD-ET reported lower balance confidence than Co were being bumped into by people while walking (p = 0.006) and walking outside on icy sidewalks (p = 0.007). On videotaped neurological examination, FD-ET were able to stand in the tandem position for fewer seconds than were Co (p = 0.048). The differences between FD-ET and Co, although statistically significant, were clinically mild. CONCLUSION: FD-ET reported more near-falls in the past year and a reduction in balance confidence; additionally, ability to maintain tandem stance was impaired compared to Co. These data suggest a more pervasive abnormality of cerebellar dysfunction than previously conceived, extending beyond ET cases themselves and manifesting in mild form in their unaffected family members.

Knowledge about Essential Tremor: A Study of Essential Tremor Families.

BACKGROUND: Essential tremor (ET) is among the most common neurological diseases and it often runs in families. How knowledgeable ET patients and their families are about their disease has been the subject of surprisingly little scholarship. METHODS: To fill this gap in knowledge, we administered a comprehensive 32-item survey (i.e., questions about etiology, pathophysiology, symptoms and signs, natural history, and treatments) to 427 participants, including 76 ET probands, 74 affected relatives (AFRs), 238 unaffected relatives, and 39 spouses of unaffected relatives, all of whom were participating in two ET family studies. We hypothesized that there would be gaps in knowledge about ET and furthermore, that probands and AFRs would be the most knowledgeable, followed by unaffected relatives and then spouses of unaffected relatives, who would be the least knowledgeable. RESULTS: Overall, ET patients lacked knowledge about their disease. Nearly one-third of probands answered "yes" or "do not know" to the question, "is ET the same or different from the type of tremor that many normal people can get when they become old and frail?" A similar proportion did not know whether children could get ET or they responded "no." Nearly one-fourth of affecteds (i.e., probands and AFRs) did not know whether or to what degree (e.g., very well, moderately well, not well) the symptoms of ET could be medically controlled, and 38.0% either reported that there was no brain surgery for ET or reported that they did not know. Nearly 17% of affecteds did not endorse genes as a cause for ET, which was surprising given the fact that this was a family study of ET. Probands and AFRs were the most knowledgeable, followed by unaffected relatives. Spouses of unaffected relatives were the least knowledgeable. CONCLUSION: We targeted a large group of ET patients and their families, as this group is perhaps most likely to be informed about the disease. ET patients and their AFRs were more knowledgeable about the features of ET than their family members without ET. Overall, however, knowledge of ET was very limited and this lack of knowledge encompassed all aspects of the disease including its underlying causes, the nature of the symptoms and signs, its natural history and its treatment. Further ET awareness education and programs targeting both families of ET patients and the public would help alleviate this gap in knowledge.

Comparative Burden of Subclinical Tremor in a Cohort of Normal Individuals Stratified by Familial Risk for Essential Tremor.

BACKGROUND: The burden of mild (i.e., subclinical) tremor within essential tremor (ET) families is not fully understood. We assessed the burden of mild tremor in a cohort of 287 adults, none of whom reported tremor or were diagnosed with ET. METHODS: We recruited adults in 2 groups based on the familial risk for ET: 244 high-risk individuals (i.e., reporting one or more first-degree relative with ET) and 43 low-risk individuals (i.e., reporting no relatives with ET). Tremor was objectively assessed on 4 hand-drawn spirals (total spiral score = 0-12). Mild tremor was defined using 3 different cut points. RESULTS: The prevalence rates of mild tremor among high-risk individuals ranged from 41.4 to 98.4% and were highly dependent on the cut point. Above a certain threshold (i.e., a total spiral score ≥5), 1-in-5 (i.e., 19.7%) high-risk individuals exhibited mild tremor, whereas no low-risk individuals did. High-risk individuals were 3.09-4.50 times more likely than low-risk individuals to exhibit mild tremor. CONCLUSION: The burden of ET extends beyond the boundaries of the clinically defined disease, and partially expressed forms of ET are abundant in ET families. This fact greatly complicates gene-finding studies and epidemiological studies whose goal is to detect disease-linked associations.

Early Head Tremor in Essential Tremor: A Case Series and Commentary.

BACKGROUND: Classically, the onset of head tremor in essential tremor (ET) patients follows that of hand tremor, such that there is a somatotopic spread of involved areas. Here we present a series of seven self-reportedly "unaffected" relatives of ET cases. These seven were clinically asymptomatic and had normal levels of arm tremor on examination, yet each evidenced a transient head wobble on examination. We estimate the prevalence of this phenotype within the two studies from which cases were ascertained. METHODS: ET cases and their self-reportedly affected and unaffected relatives, enrolled in two family studies, underwent a medical history and videotaped neurological examination. RESULTS: In seven self-reportedly "unaffected" relatives, a transient and subtle head wobble was seen, always during sustained phonation, speech, or reading aloud. Total tremor score (a measure of arm tremor) ranged from 5 to 12 (i.e., mild tremor within the range of normal). The prevalence of this phenotype of early head tremor was 3.7% in one study and 23.1% in the other. DISCUSSION: We present a series of seven individuals who had early head tremor in an evolving transition state from normal to ET. These cases raise a number of broad clinical, phenotypic, and pathophysiological issues about ET.