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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.

Objectives This study sought to investigate the impact of the neurological status of sudden cardiac arrest (SCA) survivors on implantable cardioverter-defibrillator (ICD) insertion and long-term mortality. Background The neurological status of SCA survivors may impact the decision to insert an ICD insertion and influence long-term survival. Methods In 1,433 survivors of SCA between 2002 and 2012, we examined the neurological status immediately after the arrest using the Pittsburgh Cardiac Arrest Category (PCAC) and prior to hospital discharge using the cerebral performance category (CPC) score. Patients were followed up to the endpoints of ICD implantation and all-cause mortality. Results Over a median follow-up period of 3.6 years, 389 (27%) patients received an ICD, and 674 (47%) died. The PCAC (adjusted hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.69 to 0.90) and CPC (adjusted HR: 0.73; 95% CI: 0.64 to 0.84) scores were highly predictive of the time to ICD insertion and of all-cause mortality (PCAC score, adjusted HR: 1.39; 95% CI: 1.24 to 1.57; CPC score, adjusted HR: 2.03; 95% CI: 1.77 to 2.34). ICD therapy was associated with better survival even after adjusting for neurological status (HR: 0.56; 95% CI: 0.43 to 0.73). A significant proportion of patients in the worse CPC categories had a >1-year survival after the index SCA. Conclusions In SCA survivors, worse neurological performance was associated with lower likelihood of ICD insertion and higher mortality. ICD insertion was associated with improved survival even after accounting for neurological performance. ICD discussion should therefore not be omitted in these patients.

Objectives: This study aimed to evaluate the safety and acute effect on markers of cardiac autonomic tone following pulsed electric fields (PEF) delivered to epicardial ganglionated plexi (GP) during a cardiac surgical procedure. Background: Ablation of GP as a treatment for atrial fibrillation (AF) has shown promise but thermal ablation energy sources are limited by risk of inadvertent collateral tissue injury. Methods: In acute canine experiments, median sternotomy was performed to allow identification of 5 epicardial GP regions using an anatomy-guided approach. Each site was targeted with saline-irrigated PEF (1000 V, 100 µs, 10 ECG-synchronized pulse sequences). Atrial effective refractory period (AERP) and local electrogram (EGM) amplitude were measured before and after each treatment. Histology was performed post-treatment from samples of treatment adjacent structures. Results: In 5 animals, 30 (n=2) and 60 (n=3) pulses were successfully delivered to all 5 target sites). There was no difference in local atrial EGM amplitude before and after PEF at each site (1.83{plus minus}0.41 mV vs. 1.92{plus minus}0.53 mV; p = 0.72). Mean AERP increased from 97 {plus minus} 15 ms at baseline to 115 {plus minus} 7 ms following treatment at all sites (18.6% increase, 95% CI [1.9-35.2%]; p = 0.037). There were no sustained ventricular arrhythmias or acute evidence of ischemia following delivery. Histology showed complete preservation of adjacent atrial myocardium, phrenic nerves, pericardium, and esophagus. Conclusions: The use of PEF to target regions rich in cardiac GP in open-chest canine experiments was feasible and effective at acutely altering markers of cardiac autonomic tone.

Background Slowing electrical conduction by cooling the myocardium can be used for defibrillation. We previously demonstrated the efficacy of a small cold device placed in oblique sinus (OS) in terminating atrial fibrillation (AF). However, the parameters needed to achieve effective atrial defibrillation are unknown. Purpose Assess effect of the size of cooled myocardium on frequency of AF termination in acute canine animal models. Methods Sternotomy was performed under general anesthesia in 10 acute canine experiments. AF was induced using rapid atrial pacing and intra-myocardial epinephrine and acetylcholine injections. Once AF sustained for at least 30s, either a cool (7–9°C) or placebo (body temperature) device was placed in the OS. Four device sizes were tested; ½X½, ¾X¾, and 1X1 inch devices and two ¾X¾ inch devices placed side by side simultaneously. Time to AF termination was recorded. Chi-squared or Fisher's exact test were used to compare the frequency of arrhythmia termination with cooling versus placebo. Results A total of 166 applications were performed (89 cool vs 77 placebo) in 10 animal experiments. Overall, AF terminated in 82% of the cooling applications vs. 67.5% of placebo (P=0.03, Figure 1). For the ½X½ inch device 88% of cold applications restored sinus rhythm vs. 63.6% for placebo (P=0.05). The frequency of sinus restoration for cold ¾X¾, 1X1 and two ¾X¾ side by side devices was 86.7%, 83.3% and 70% respectively. Time to sinus restoration when achieved was within three minutes was also not significantly changed. Conclusion Placing a cool device in the oblique sinus can terminate AF and efficacy is not affected by the size of device. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): MediCool Technologies

Background We have demonstrated that artificial intelligence interpretation of ECGs (AI-ECG) can estimate an individual's physiologic age and that the gap between AI-ECG and chronologic age (Age-Gap) is associated with increased mortality. We hypothesized that Age-Gap would predict long-term atherosclerotic cardiovascular disease (ASCVD) and that Age-Gap would refine the ACC/AHA Pooled Cohort Equations' (PCE) predictive abilities. Methods Using the Rochester Epidemiology Project (REP) we evaluated a community-based cohort of consecutive patients seeking primary care between 1998–2000 and followed through March 2016. Inclusion criteria were age 40–79 and complete data to calculate PCE. We excluded those with known ASCVD, AF, HF or an event within 30 days of baseline.A neural network, trained, validated, and tested in an independent cohort of ∼ 500,000 independent patients, using 10-second digital samples of raw, 12 lead ECGs. PCE was categorized as low Results We included 24,793 patients (54% women, 95% Caucasian) with mean follow up of 12.6±5.1 years. 2,366 (9.5%) developed ASCVD events and 3,401 (13.7%) the expanded ASCVD. Mean chronologic age was 53.6±11.6 years and the AI-ECG age was 54.5±10.9 years, R2=0.7865, p20%) age and sex adjusted HR 6.90, 95% CI 1.98–24.08, p-value=0.0006, when comparing those older to younger by ECG respectively (Figure 1B). Conclusion The difference between physiologic AI-ECG age and chronologic age is associated with long-term ASCVD, and enhances current risk calculators (PCE) ability to identify high and low risk individuals. This may help identify individuals who should or should not be treated with newer, expensive risk-reducing therapies. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Clinic

BACKGROUND: Although elevated body mass index (BMI) is a risk factor for cardiac disease, patients with elevated BMI have better survival in the context of severe illness, a phenomenon termed the “obesity paradox.” HYPOTHESIS: Higher BMI is associated with lower mortality in sudden cardiac arrest (SCA) survivors. METHODS: Data were collected on 1433 post‐SCA patients, discharged alive from the hospitals of the University of Pittsburgh Medical Center between 2002 and 2012. Of those, 1298 patients with documented BMI during the index hospitalization and follow‐up data constituted the study cohort. RESULTS: In the overall cohort, 30 patients were underweight (BMI

Clinical heart failure (HF) occurs frequently after ST-segment elevation myocardial infarction (STEMI), and is associated with increased mortality. We assessed the impact of remote ischemic peri-conditioning (RIPC) during inter-facility air medical transport of STEMI patients on clinical HF following primary percutaneous coronary intervention (pPCI).Data from Acute Coronary Treatment and Intervention Outcomes Network Registry®-Get With the Guidelines™ (ACTION Registry-GWTG) from two PCI-hospitals that are utilizing RIPC during inter-facility helicopter transport of STEMI patients for pPCI between March, 2013 and September, 2015 were used for this study. The analyses were limited to inter-facility STEMI patients transported by helicopter with LVEF55% after pPCI. The outcome measures were occurrence of clinical HF and serum level of brain-type natriuretic peptide (BNP).Out of the 150 STEMI patients in this analysis, 92 patients received RIPC and 58 did not. The RIPC and non-RIPC groups were generally similar in demographic and clinical characteristics except for lower incidence of cardiac arrest in the RIPC group (3/92 [3.3%] versus 13/58 [22.4%], p=0.002). STEMI patients who received RIPC were less likely to have in-hospital clinical HF compared to patients who did not receive RIPC (3/92 [3.3%] versus 7/58 [12.1%]; adjusted OR=0.22, 95% CI 0.05-0.92, p=0.038) after adjusting for baseline differences. In subgroup analysis, RIPC was associated with lower BNP (123 [interquartile range, 17.0-310] versus 319 [interquartile range, 106-552], p=0.029).RIPC applied during inter-facility air transport of STEMI patients for pPCI is associated with reduced incidence of clinical HF and serum BNP.

Objective To assess the impact of remote ischemic peri-conditioning (RIPC) during inter-facility air medical transport of ST-segment elevation myocardial infarction (STEMI) patients on the incidence of acute kidney injury (AKI) following primary percutaneous coronary intervention (pPCI). Background STEMI patients who receive pPCI have an increased risk of AKI for which there is no well-defined prophylactic therapy in the setting of emergent pPCI. Methods Using the ACTION Registry-GWTG, we evaluated the impact of RIPC applied during inter-facility helicopter transport of STEMI patients from non-PCI capable hospitals to 2 PCI-hospitals in the United States between March, 2013 and September, 2015 on the incidence of AKI following pPCI. AKI was defined as ≥0.3 mg/dL increase in creatinine within 48–72 hours after pPCI. Results Patients who received RIPC (n = 127), compared to those who did not (n = 92), were less likely to have AKI (11 of 127 patients [8.7%] vs. 17 of 92 patients [18.5%]; adjusted odds ratio = 0.32, 95% CI 0.12–0.85, P = 0.023) and all-cause in-hospital mortality (2 of 127 patients [1.6%] vs. 7 of 92 patients [7.6%]; adjusted odds ratio = 0.14, 95% CI 0.02–0.86, P = 0.034) after adjusting for socio-demographic and clinical characteristics. There was no difference in hospital length of stay (3 days [interquartile range, 2–4] vs. 3 days [interquartile range, 2–5], P = 0.357) between the 2 groups. Conclusion RIPC applied during inter-facility helicopter transport of STEMI patients for pPCI is associated with lower incidence of AKI and in-hospital mortality. The use of RIPC for renal protection in STEMI patients warrants further in depth investigation.

The vast majority of pacemaker systems are implanted through the transvenous approach which conveys many potential challenges and complications. The benefits of ventricular resynchronization are well established and there is mounting evidence for the use of atrial resynchronization in heart failure

Artificial intelligence interpretation of ECGs can estimate ECG Age. This can vary from chronologic age (AGE) and may reflect random error, comorbidities or physiologic age. We assessed if ECG Age minus AGE (Age-Gap) correlates with mortality, an outcome measure of physiologic aging. We developed a

BACKGROUND There is insufficient information about the long-term prognosis of sudden cardiac arrest (SCA) survivors. We therefore derived a clinical score (Sudden Cardiac Arrest-mortality score, SCA-MS) that predicts long-term mortality in patients surviving to hospital discharge and validated it in an independent cohort of SCA survivors. METHODS A total of 1433 SCA survivors data were collected, who were discharged from the hospitals of the University of Pittsburgh Medical Center between 2002 and 2012. The overall cohort was randomly divided into two near equal cohorts used for the derivation and validation of the SCA-MS, respectively. RESULTS The derivation cohort included 768 patients and identified serum potassium level>4.2 mg/dL at admission, the presence of atrial fibrillation at any time during the index hospitalization, and the presence of asystole or pulseless electrical activity as the initial documented rhythm as independent predictors of long-term mortality. Based on the multivariable modeling result, one point was assigned to each one of these variables to create the SCA-MS that ranged from 0 to 3. In the validation cohort, the SCA-MS was predictive of long-term mortality (hazards ratio = 1.69, 95% confidence interval 1.50-1.91, P

Background: Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy in survivors of sudden cardiac arrest (SCA), except in those with completely reversible causes. We sought to examine the impact of ICD therapy on mortality in survivors of SCA associated with reversible causes. Methods and Results: We evaluated the records of 1433 patients managed at our institution between 2000 and 2012 who were discharged alive after SCA. A reversible and correctable cause was identified in 792 (55%) patients. Reversible SCA cause was defined as significant electrolyte or metabolic abnormality, evidence of acute myocardial infarction or ischemia, recent initiation of antiarrhythmic drug or illicit drug use, or other reversible circumstances. Of the 792 SCA survivors because of a reversible and correctable cause (age 61±15 years, 40% women), 207 (26%) patients received an ICD after their index SCA. During a mean follow-up of 3.8±3.1 years, 319 (40%) patients died. ICD implantation was highly associated with lower all-cause mortality ( P P P Conclusions: In survivors of SCA because of a reversible and correctable cause, ICD therapy is associated with lower all-cause mortality except if the SCA was because of myocardial infarction. These data deserve further investigation in a prospective multicenter randomized controlled trial, as they may have important and immediate clinical implications.

Patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) have a markedly increased risk of developing acute kidney injury (AKI), and diabetic patients have worse outcomes. Recent studies suggest that remote ischemic peri