Automated interpretations of single-lead electrocardiograms predict incident atrial fibrillation: The VITAL-AF trial.

BACKGROUND: Single-lead electrocardiograms (1L ECGs) are increasingly used for atrial fibrillation (AF) detection. Automated 1L ECG interpretation may have prognostic value for future AF in cases in which screening does not result in a short-term AF diagnosis. OBJECTIVE: We sought to investigate the association between automated 1L ECG interpretation and incident AF. METHODS: VITAL-AF was a randomized controlled trial investigating the effectiveness of screening for AF by 1L ECGs. For this study, participants were divided into 4 groups based on automated classification of 1L ECGs. Patients with prevalent AF were excluded. Associations between groups and incident AF were assessed by Cox proportional hazards models adjusted for risk factors. The start of follow-up was defined as 60 days after the latest 1L ECG (as some individuals had numerous screening 1L ECGs). RESULTS: The study sample included never screened (n = 16,306), normal (n = 10,914), other (n = 2675), and possible AF (n = 561). Possible AF had the highest AF incidence (5.91 per 100 person-years; 95% confidence interval [CI], 4.24-8.23). Possible AF was associated with greater hazard of incident AF compared with normal (adjusted hazard ratio, 2.48; 95% CI, 1.66-3.71). Other was associated with greater hazard of incident AF compared with normal (1.41; 95% CI, 1.04-1.90). CONCLUSION: In patients undergoing AF screening with 1L ECGs without prevalent AF or AF within 60 days of screening, presumptive positive and indeterminate 1L ECG interpretations were associated with future AF. Abnormal 1L ECG recordings may identify individuals at higher risk for future AF.

Accuracy and variability of cardiologist interpretation of single lead electrocardiograms for atrial fibrillation: The VITAL-AF trial.

BACKGROUND: Screening for atrial fibrillation (AF) using consumer-based devices capable of producing a single lead electrocardiogram (1L ECG) is increasing. There are limited data on the accuracy of physician interpretation of these tracings. The goal of this study is to assess the sensitivity, specificity, confidence, and variability of cardiologist interpretation of point-of-care 1L ECGs. METHODS: Fifteen cardiologists reviewed point-of-care handheld 1L ECGs collected from patients aged 65 years or older enrolled in the VITAL-AF clinical trial [NCT035115057] who underwent cardiac rhythm assessments with a 1L ECG using an AliveCor KardiaMobile device. Random sampling of 1L ECGs for cardiologist review was stratified by the AliveCor algorithm interpretation. A 12L ECG performed on the same day for clinical purposes was used as the gold standard. Cardiologists each reviewed a common sample of 200 1L ECG tracings and completed a survey associated with each tracing. Cardiologists were blinded to both the AliveCor algorithm and same day 12L ECG interpretation. For each tracing, study cardiologists were asked to assess the rhythm (sinus rhythm, AF, unclassifiable), report their assessment of the quality of the tracing, and rate their confidence in rhythm interpretation. The outcomes included the sensitivity, specificity, variability, and confidence in physician interpretation. Variables associated with each measure were identified using multivariable regression. RESULTS: The average sensitivity for AF was 77.4% (range 50%-90.6%, standard deviation [SD]=11.4%) and the average specificity was 73.0% (range 41.3%-94.6%, SD = 15.4%). The mean variability was 30.8% (range 0%-76.2%, SD = 23.2%). The average reviewer confidence of 1L ECG rhythm assessment was 3.6 out of 5 (range 2.5-4.2, SD = 0.6). Patient and tracing factors associated with sensitivity, specificity, variability, and confidence were identified and included age, body mass index, and presence of artifact. CONCLUSION: Cardiologist interpretation of point-of-care handheld 1L ECGs has modest diagnostic sensitivity and specificity with substantial variability for AF classification despite high confidence. Variability in cardiologist interpretation of 1L ECGs highlights the importance of confirmatory testing for diagnosing AF.

Cardiac Contractility Modulation for Heart Failure: Current and Future Directions.

Cardiac contractility modulation (CCM) is a Food and Drug Administration-approved device-based therapy for patients with heart failure. The system delivers biphasic electric stimulation to the ventricular myocardium during the absolute refractory period to augment left ventricular contraction. CCM therapy promotes acute and chronic changes at the cellular level, leading to favorable remodeling throughout the myocardium. CCM improves quality of life, New York Heart Association class, left ventricular ejection fraction, peak oxygen uptake, and the composite end point of cardiovascular death and heart failure hospitalizations. This review will focus on the biological basis, indications, and evidence for CCM, as well as the future applications of this technology.

Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus. METHODS AND RESULTS: In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%. CONCLUSION: Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC.

Cardiovascular Mortality After Type 1 and Type 2 Myocardial Infarction in Young Adults.

BACKGROUND: Type 2 myocardial infarction (MI) and myocardial injury are associated with increased short-term mortality. However, data regarding long-term mortality are lacking. OBJECTIVES: This study compared long-term mortality among young adults with type 1 MI, type 2 MI, or myocardial injury. METHODS: Adults age 50 years or younger who presented with troponin >99th percentile or the International Classification of Diseases code for MI over a 17-year period were identified. All cases were adjudicated as type 1 MI, type 2 MI, or myocardial injury based on the Fourth Universal Definition of MI. Cox proportional hazards models were constructed for survival free from all-cause and cardiovascular death. RESULTS: The cohort consisted of 3,829 patients (median age 44 years; 30% women); 55% had type 1 MI, 32% had type 2 MI, and 13% had myocardial injury. Over a median follow-up of 10.2 years, mortality was highest for myocardial injury (45.6%), followed by type 2 MI (34.2%) and type 1 MI (12%) (p < 0.001). In an adjusted model, type 2 MI was associated with higher all-cause (hazard ratio: 1.8; 95% confidence interval: 1.2 to 2.7; p = 0.004) and cardiovascular mortality (hazard ratio: 2.7; 95% confidence interval: 1.4 to 5.1; p = 0.003) compared with type 1 MI. Those with type 2 MI or myocardial injury were younger and had fewer cardiovascular risk factors but had more noncardiovascular comorbidities. They were significantly less likely to be prescribed cardiovascular medications at discharge. CONCLUSIONS: Young patients who experience a type 2 MI have higher long-term all-cause and cardiovascular mortality than those who experience type 1 MI, with nearly one-half of patients with myocardial injury and more than one-third of patients with type 2 MI dying within 10 years. These findings emphasize the need to provide more aggressive secondary prevention for patients who experience type 2 MI and myocardial injury.

Novel calmodulin mutations associated with congenital long QT syndrome affect calcium current in human cardiomyocytes.

BACKGROUND: Calmodulin (CaM) mutations are associated with cardiac arrhythmia susceptibility including congenital long QT syndrome (LQTS). OBJECTIVE: The purpose of this study was to determine the clinical, genetic, and functional features of 2 novel CaM mutations in children with life-threatening ventricular arrhythmias. METHODS: The clinical and genetic features of 2 congenital arrhythmia cases associated with 2 novel CaM gene mutations were ascertained. Biochemical and functional investigations were conducted on the 2 mutations. RESULTS: A novel de novo CALM2 mutation (D132H) was discovered by candidate gene screening in a male infant with prenatal bradycardia born to healthy parents. Postnatal course was complicated by profound bradycardia, prolonged corrected QT interval (651 ms), 2:1 atrioventricular block, and cardiogenic shock. He was resuscitated and was treated with a cardiac device. A second novel de novo mutation in CALM1 (D132V) was discovered by clinical exome sequencing in a 3-year-old boy who suffered a witnessed cardiac arrest secondary to ventricular fibrillation. Electrocardiographic recording after successful resuscitation revealed a prolonged corrected QT interval of 574 ms. The Ca(2+) affinity of CaM-D132H and CaM-D132V revealed extremely weak binding to the C-terminal domain, with significant structural perturbations noted for D132H. Voltage-clamp recordings of human induced pluripotent stem cell-derived cardiomyocytes transiently expressing wild-type or mutant CaM demonstrated that both mutations caused impaired Ca(2+)-dependent inactivation of voltage-gated Ca(2+) current. Neither mutant affected voltage-dependent inactivation. CONCLUSION: Our findings implicate impaired Ca(2+)-dependent inactivation in human cardiomyocytes as the plausible mechanism for long QT syndrome associated with 2 novel CaM mutations. The data further expand the spectrum of genotype and phenotype associated with calmodulinopathy.

Prevalence and predictors of atrial fibrillation among patients undergoing bariatric surgery.

BACKGROUND: While AF is a disease of the elderly, it can occur earlier in the presence of risk factors such as obesity. Bariatric surgery patients are significantly younger and more obese than previously described populations with AF. Therefore, it remains to be determined whether current estimates of the prevalence and predictors for AF remain true in the bariatric surgery population. METHODS: We performed a cross-sectional analysis of 1,341 consecutive patients who underwent bariatric surgery from January 2008 to October 2012. Baseline characteristics were compared between patients with and without AF. For additional comparison, 176 patients with AF and body mass index (BMI) >40 kg/m(2) were identified from the Vanderbilt AF Registry. A multivariable logistic regression was performed to identify predictors of AF within the bariatric surgery cohort. RESULTS: The prevalence of AF in the bariatric surgery cohort was 1.9 % (25/1,341). Patients with AF were older (median 56 years (interquartile range [52-64) vs.46 [38-56] years, p < 0.001), were more often male (48 vs. 23 %, p = 0.004), had more comorbidities, but had no difference in BMI (50 kg/m(2) [44-58] vs. 48 [43-54], p = 0.4). In multivariable analysis, the odds of AF increased 2.2-fold by age per decade (95 % CI, 1.4-3.5; p < 0.001) and 2.4-fold by male gender (1.1-5.4, p = 0.03) when adjusted for BMI. BMI was not independently associated with AF (OR 1.15 [95 % CI, 0.98-1.41], p = 0.09). CONCLUSIONS: The prevalence of AF is 1.9 % among patients undergoing bariatric surgery. Risk of AF was found to increase with age and male gender, but not with higher BMI.