Kapa, Suraj

Abstract Background We have demonstrated that a neural network is able to predict a person’s age from the electrocardiogram (ECG) [artificial intelligence (AI) ECG age]. However, some discrepancies were observed between ECG-derived and chronological ages. We assessed whether the difference between AI ECG and chronological age (Age-Gap) represents biological ageing and predicts long-term outcomes. Methods and results We previously developed a convolutional neural network to predict chronological age from ECGs. In this study, we used the network to analyse standard digital 12-lead ECGs in a cohort of 25 144 subjects ≥30 years who had primary care outpatient visits from 1997 to 2003. Subjects with coronary artery disease, stroke, and atrial fibrillation were excluded. We tested whether Age-Gap was correlated with total and cardiovascular mortality. Of 25 144 subjects tested (54% females, 95% Caucasian) followed for 12.4 ± 5.3 years, the mean chronological age was 53.7 ± 11.6 years and ECG-derived age was 54.6 ± 11 years (R2 = 0.79, P < 0.0001). The mean Age-Gap was small at 0.88 ± 7.4 years. Compared to those whose ECG-derived age was within 1 standard deviation (SD) of their chronological age, patients with Age-Gap ≥1 SD had higher all-cause and cardiovascular disease (CVD) mortality. Conversely, subjects whose Age-Gap was ≤1 SD had lower all-cause and CVD mortality. Results were unchanged after adjusting for CVD risk factors and other survival influencing factors. Conclusion The difference between AI ECG and chronological age is an independent predictor of all-cause and cardiovascular mortality. Discrepancies between these possibly reflect disease independent biological ageing.

Background An artificial intelligence algorithm that detects age using the 12‐lead ECG has been suggested to signal “physiologic age.” This study aimed to investigate the association of peripheral microvascular endothelial function (PMEF) as an index of vascular aging, with accelerated physiologic aging gauged by ECG‐derived artificial intelligence–estimated age. Methods and Results This study included 531 patients who underwent ECG and a noninvasive PMEF assessment using reactive hyperemia peripheral arterial tonometry. Abnormal PMEF was defined as reactive hyperemia peripheral arterial tonometry index ≤2.0. Accelerated or delayed physiologic aging was calculated by the Δ age (ECG‐derived artificial intelligence–estimated age minus chronological age), and the association between Δ age and PMEF as well as its impact on composite major adverse cardiovascular events were investigated. Δ age was higher in patients with abnormal PMEF than in patients with normal PMEF (2.3±7.8 versus 0.5±7.7 years; P =0.01). Reactive hyperemia peripheral arterial tonometry index was negatively associated with Δ age after adjustment for cardiovascular risk factors (standardized β coefficient, –0.08; P =0.048). The highest quartile of Δ age was associated with an increased risk of major adverse cardiovascular events compared with the first quartile of Δ age in patients with abnormal PMEF, even after adjustment for cardiovascular risk factors (hazard ratio, 4.72; 95% CI, 1.24–17.91; P =0.02). Conclusions Vascular aging detected by endothelial function is associated with accelerated physiologic aging, as assessed by the artificial intelligence–ECG Δ age. Patients with endothelial dysfunction and the highest quartile of accelerated physiologic aging have a marked increase in risk for cardiovascular events.

Background The prognosis of left ventricular noncompaction (LVNC) remains elusive despite its recognition as a clinical entity for >30 years. We sought to identify clinical and imaging characteristics and risk factors for mortality in patients with LVNC. Methods and Results 339 adults with LVNC seen between 2000 and 2016 were identified. LVNC was defined as end‐systolic noncompacted to compacted myocardial ratio >2 (Jenni criteria) and end‐diastolic trough of trabeculation‐to‐epicardium (X):peak of trabeculation‐to‐epicardium (Y) ratio <0.5 (Chin criteria) by echocardiography; and end‐diastolic noncompacted:compacted ratio >2.3 (Petersen criteria) by magnetic resonance imaging. Median age was 47.4 years, and 46% of patients were female. Left ventricular ejection fraction <50% was present in 57% of patients and isolated apical noncompaction in 48%. During a median follow‐up of 6.3 years, 59 patients died. On multivariable Cox regression analysis, age (hazard ratio [HR] 1.04; 95% CI, 1.02–1.06), left ventricular ejection fraction <50% (HR, 2.37; 95% CI, 1.17–4.80), and noncompaction extending from the apex to the mid or basal segments (HR, 2.11; 95% CI, 1.21–3.68) were associated with all‐cause mortality. Compared with the expected survival for age‐ and sex‐matched US population, patients with LVNC had reduced overall survival ( P <0.001). However, patients with LVNC with preserved left ventricular ejection fraction and patients with isolated apical noncompaction had similar survival to the general population. Conclusions Overall survival is reduced in patients with LVNC compared with the expected survival of age‐ and sex‐matched US population. However, survival rate in those with preserved left ventricular ejection fraction and isolated apical noncompaction was comparable with that of the general population.

Abstract Aims An artificial intelligence-augmented electrocardiogram (AI-ECG) algorithm can identify left ventricular systolic dysfunction (LVSD). We sought to determine whether this AI-ECG algorithm could stratify mortality risk in cardiac intensive care unit (CICU) patients, independent of the presence of LVSD by transthoracic echocardiography (TTE). Methods and results We included 11 266 unique Mayo Clinic CICU patients admitted from 2007 to 2018 who underwent AI-ECG after CICU admission. Left ventricular ejection fraction (LVEF) data were extracted for patients with a TTE during hospitalization. Hospital mortality was analysed using multivariable logistic regression. Mean age was 68 ± 15 years, including 37% females. Higher AI-ECG probability of LVSD remained associated with higher hospital mortality [adjusted odds ratio (OR) 1.05 per 0.1 higher, 95% confidence interval (CI) 1.02–1.08, P = 0.003] after adjustment for LVEF, which itself was inversely related with the risk of hospital mortality (adjusted OR 0.96 per 5% higher, 95% CI 0.93–0.99, P = 0.02). Patients with available LVEF data (n = 8242) were divided based on the presence of predicted (by AI-ECG) vs. observed (by TTE) LVSD (defined as LVEF ≤ 35%), using TTE as the gold standard. A stepwise increase in hospital mortality was observed for patients with a true negative, false positive, false negative, and true positive AI-ECG. Conclusion The AI-ECG prediction of LVSD is associated with hospital mortality in CICU patients, affording risk stratification in addition to that provided by echocardiographic LVEF. Our results emphasize the prognostic value of electrocardiographic patterns reflecting underlying myocardial disease that are recognized by the AI-ECG.

AbstractIntroductionTherapies for substrate‐related arrhythmias include ablation or drugs targeted at altering conductive properties or disruption of slow zones in heterogeneous myocardium. Conductive compounds such as carbon nanotubes may provide a novel personalizable therapy for arrhythmia treatment by allowing tissue homogenization.MethodsA nanocellulose carbon nanotube‐conductive hydrogel was developed to have conduction properties similar to normal myocardium. Ex vivo perfused canine hearts were studied. Electroanatomic activation mapping of the epicardial surface was performed at baseline, after radiofrequency ablation, and after uniform needle injections of the conductive hydrogel through the injured tissue. Gross histology was used to assess distribution of conductive hydrogel in the tissue.ResultsThe conductive hydrogel viscosity was optimized to decrease with increasing shear rate to allow expression through a syringe. The direct current conductivity under aqueous conduction was 4.3 × 10−1 S/cm. In four canine hearts, when compared with the homogeneous baseline conduction, isochronal maps demonstrated sequential myocardial activation with a shift in direction of activation to surround the edges of the ablated region. After injection of the conductive hydrogel, isochrones demonstrated conduction through the ablated tissue with activation restored through the ablated tissue. Gross specimen examination demonstrated retention of the hydrogel within the tissue.ConclusionsThis proof‐of‐concept study demonstrates that conductive hydrogel can be injected into acutely disrupted myocardium to restore conduction. Future experiments should focus on evaluating long‐term retention and biocompatibility of the hydrogel through in vivo experimentation.

To our knowledge, natural history has not been reported for cardiac sarcoidosis (CS) diagnosed by pathologic evaluation of the apical core at left ventricular assist device (LVAD) implantation or cardiac transplantation. We retrospectively identified 232 consecutive patients meeting CS criteria. Of these patients, 54 were diagnosed by pathologic confirmation of CS, 10 after evaluation of the apical core (LVAD implant) or explanted heart (transplant). We compared clinical characteristics at initial evaluation and outcomes for these 10 patients with those of 10 patients with known CS before LVAD implant/transplant. In the study group, five patients (50%) had confirmed extracardiac sarcoidosis before LVAD implant/transplant; five had not been diagnosed with sarcoidosis. Mean (standard deviation) left ventricular ejection fraction at initial evaluation was 23% (16%), and left ventricular end-diastolic dimension was 61 (10) mm. Four patients died during follow-up; however, no survival difference was found for the 10 patients diagnosed incidentally and the group with a previous diagnosis or institutional LVAD/transplant cohorts. Patients diagnosed with CS on pathological examination of the apical core/explanted heart may have severe dilated cardiomyopathy as the initial presentation. Outcomes for patients with CS after advanced heart failure therapies may be comparable with those of non-CS patients.

AbstractAims The Food and Drug Administration (FDA) approval of the Watchman device [percutaneous left atrial appendage occlusion (LAAO)] has resulted in the widespread use of this procedure in many centres across the USA. We sought to estimate the nationwide utilization and frequency of adverse outcomes associated with Watchman device implantation. The objective of this study was to evaluate the Watchman device implantation peri-procedural complications and comparison of the results with the previous studies.Methods and results The National Inpatient Sample (NIS) was queried for all hospitalizations with a primary diagnosis of atrial fibrillation or atrial flutter during the year 2016 with percutaneous LAAO during the same admission (ICD-10 code—02L73DK). The frequency of peri-procedural complications, including mortality, procedure-related stroke, major bleeding requiring blood transfusion, and pericardial effusion, was assessed. We compared the complication rates with the published randomized controlled trials and the European Watchman registry. An estimated 5175 LAAO procedures were performed in 2016. The majority of procedures was performed in males (59.1%), age ≥75 years (58.7%), and White (83.1%). The overall complication rate was 1.9%. The in-hospital mortality was 0.29%. Pericardial effusion requiring pericardiocentesis was the most frequent complication (0.68%). Bleeding requiring transfusion was noted in 0.1% of device implants. The rates of post-procedure stroke and systemic embolism were 0% and 0.29%, respectively.Conclusion Percutaneous LAAO with the Watchman device in the USA is associated with low in-hospital complications and a similar safety profile to a recently published EWOLUTION cohort. The complication rates were lower than those reported in the major randomized clinical trials (RCTs). We report the frequency of peri-procedural complications of the LAAO using the Watchman device from the NIS database. We also compare the frequency of peri-procedural complications with the previously published RCTs and EWOLUTION cohort. Our findings are in concordance with findings from EWOLUTION cohort and compare favourably with RCTs.

AbstractBackgroundMagnetic resonance imaging (MRI) in patients with legacy cardiovascular implantable electronic devices (CIEDs) in situ is likely underutilized. We hypothesized the clinical benefit of MRI would outweigh the risks in legacy CIED patients.MethodsThis is a single‐center retrospective study that evaluated and classified the utility of MRI using a prospectively maintained database. The outcomes were classified as aiding in diagnosis, treatment, or both for the patients attributable to the MRI. We then assessed the incidence of adverse effects (AE) when the MRI was performed.ResultsIn 668, MRIs performed on 479 patients, only 13 (1.9%) MRIs did not aid in the diagnosis or treatment of the patient. Power‐on reset events without clinical sequelae in three scans (0.45%) were the only AE. The probability of an adverse event happening without any benefit from the MRI scan was 1.1 × 10−4. A maximum benefit in diagnosis using MRI was obtained in ruling out space‐occupying lesions (121/185 scans, 65.4%). Scans performed in patients for elucidating answers to queries in treatment were most frequently done for disease staging at long term follow‐up (167/470 scans, 35.5%). Conservative treatment (184/470 scans, 39%) followed by medication changes (153/470 scans, 28.7%) were the most common treatment decisions made.ConclusionsThe utility of MRI in patients with non‐MRI‐conditional CIEDs far outweighs the risk of adverse events when imaging is done in the context of a multidisciplinary program that oversees patient safety.

AbstractIntroductionThe ablation of outflow tract premature ventricular contractions (PVCs) is generally safe and effective. In some patients, successful ablation sites may not correlate with the earliest activation. We sought to evaluate mechanistic and anatomic relevance of the region below the left sinus of Valsalva in variable morphology outflow tract ventricular arrhythmias.MethodsPVC cases where ablation was in the region inferior to the left sinus of Valsalva were identified. Procedural and demographic information and long‐term outcomes were obtained. Cadaver dissections to evaluate regional anatomy were done as well.ResultsA total of 51 cases were included (age 53 ± 10; 37 [73%] males). Ablation was done for high PVC burden (>20%; mean 27% ± 8%) and presence of symptoms (73%) or ejection fraction less than 50% (78%). QRS morphology included either R wave (8; 16%), Rs (9; 18%), or rS (67%) in lead I, no precordial transition (40; 78%), V2 transition, (7; 14%), or V3 transition (4; 8%). In 31 (61%), the site just below the left coronary cusp was the earliest site, while the remainder had another site earlier. Ablation was acutely successful in 50 of 51 (98%). After 3 months, success was noted in 48 of 51 (94%). In two patients, repeat ablation in the same region resulted in durable suppression.ConclusionThe cases presented emphasize the importance of a region centered below the left sinus of Valsalva, where multivariable morphology QRS may be successfully ablated. Consideration of mapping and ablation even when signals are late in this region may be warranted in previously failed ablation attempts or first‐line evaluation.

AbstractBackgroundInappropriate sinus tachycardia (IST) remains a clinical challenge because patients often are highly symptomatic and not responsive to medical therapy.ObjectiveTo study the safety and efficacy of stellate ganglion (SG) block and cardiac sympathetic denervation (CSD) in patients with IST.MethodsTwelve consecutive patients who had drug‐refractory IST (10 women) were studied. According to a prospectively initiated protocol, five patients underwent an electrophysiologic study before and after SG block (electrophysiology study group). The subsequent seven patients had ambulatory Holter monitoring before and after SG block (ambulatory group). All patients underwent SG block on the right side first, and then on the left side. Selected patients who had heart rate reduction ≥15 beats per minute (bpm) were recommended to consider CSD.ResultsThe mean (SD) baseline heart rate (HR) was 106 (21) bpm. The HR significantly decreased to 93 (20) bpm (P = .02) at 10 minutes after right SG block and remained significantly slower at 97(19) bpm at 60 minutes. Left SG block reduced HR from 99 (21) to 87(16) bpm (P = .02) at 60 minutes. SG block had no significant effect on blood pressure or HR response to isoproterenol or exercise (all P > .05). Five patients underwent right (n = 4) or bilateral (n = 1) CSD. The clinical outcomes were heterogeneous: one patient had complete and two had partial symptomatic relief, and two did not have improvement.ConclusionSG blockade modestly reduces resting HR but has no significant effect on HR during exercise. Permanent CSD may have a modest role in alleviating symptoms in selected patients with IST.