Artificial Intelligence and Machine Learning in Arrhythmias and Cardiac Electrophysiology.

Artificial intelligence (AI) and machine learning (ML) in medicine are currently areas of intense exploration, showing potential to automate human tasks and even perform tasks beyond human capabilities. Literacy and understanding of AI/ML methods are becoming increasingly important to researchers and clinicians. The first objective of this review is to provide the novice reader with literacy of AI/ML methods and provide a foundation for how one might conduct an ML study. We provide a technical overview of some of the most commonly used terms, techniques, and challenges in AI/ML studies, with reference to recent studies in cardiac electrophysiology to illustrate key points. The second objective of this review is to use examples from recent literature to discuss how AI and ML are changing clinical practice and research in cardiac electrophysiology, with emphasis on disease detection and diagnosis, prediction of patient outcomes, and novel characterization of disease. The final objective is to highlight important considerations and challenges for appropriate validation, adoption, and deployment of AI technologies into clinical practice.

Advances in Atrial Fibrillation Ablation: Energy Sources Here to Stay.

Energy sources used for catheter ablation of atrial fibrillation (AF) ablation have undergone an exceptional journey over the past 50 years. Traditional energy sources, such as radiofrequency and cryoablation, have been the mainstay of AF ablation. Novel investigations have led to inclusion of other techniques, such as laser, high-frequency ultrasound, and microwave energy, in the armamentarium of electrophysiologists. Despite these modalities, AF has remained one of the most challenging arrhythmias. Advances in the understanding of electroporation promise to overcome the shortcomings of conventional energy sources. A thorough understanding of the biophysics and practical implications of the existing energy sources is paramount.

Year in Review in Cardiac Electrophysiology.

In the past year, there have been numerous advances in our understanding of arrhythmia mechanisms, diagnosis, and new therapies. We have seen advances in basic cardiac electrophysiology with data suggesting that secretoneurin may be a biomarker for patients at risk of ventricular arrhythmias, and we have learned of the potential role of an NPR-C (natriuretic peptide receptor-C) in atrial fibrosis and the role of an atrial specific 2-pore potassium channel TASK-1 as a therapeutic target for atrial fibrillation. We have seen studies demonstrating the role of sensory neurons in sleep apnea-related atrial fibrillation and the association between bariatric surgery and atrial fibrillation ablation outcomes. Artificial intelligence applied to electrocardiography has yielded estimates of age, sex, and overall health. We have seen new tools for collection of patient-centered outcomes following catheter ablation. There have been significant advances in the ability to identify ventricular tachycardia termination sites through high-density mapping of deceleration zones. We have learned that right ventricular dysfunction may be a predictor of survival benefit after implantable cardioverter-defibrillator implantation in patients with nonischemic cardiomyopathy. We have seen further insights into the role of His bundle pacing on improving outcomes. As our understanding of cardiac laminopathies advances, we may have new tools to predict arrhythmic event rates in gene carriers. Finally, we have seen numerous advances in the treatment of arrhythmias in patients with congenital heart disease.

Left sinus of Valsalva-Electroanatomic basis and outcomes with ablation for outflow tract arrhythmias.

INTRODUCTION: The 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. METHODS: PVC 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. RESULTS: A 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. CONCLUSION: The 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.

Modulation of the autonomic nervous system through mind and body practices as a treatment for atrial fibrillation.

Atrial fibrillation is the most common symptomatic arrhythmia that is associated with stroke. Contemporary management of the disease is focused on anticoagulation to prevent stroke, coupled with catheter ablation to limit symptoms and prevent deleterious cardiac remodeling. Emerging data highlights the importance of lifestyle modification by managing sleep apnea, increasing physical activity, and weight loss. There is significant data that supports a link between the autonomic nervous system, arrhythmia development, and atrial fibrillation therapy. It is likely that lifestyle modification through these techniques that are aimed to reduce stress may also mediate atrial fibrillation development through this mechanism. This review examines how mind and body practices such as meditation, yoga, and acupuncture may influence the autonomic nervous system and mitigate atrial fibrillation progression and regression. Available evidence from molecular and anatomical levels through to clinical observations and translational clinical trials were scrutinized and a case established for these interventions as potential powerful mediators of anti-arrhythmic benefit.

Stellate ganglion block and cardiac sympathetic denervation in patients with inappropriate sinus tachycardia.

BACKGROUND: Inappropriate sinus tachycardia (IST) remains a clinical challenge because patients often are highly symptomatic and not responsive to medical therapy. OBJECTIVE: To study the safety and efficacy of stellate ganglion (SG) block and cardiac sympathetic denervation (CSD) in patients with IST. METHODS: Twelve 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. RESULTS: The 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. CONCLUSION: SG 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.

Elimination of Purkinje Fibers by Electroporation Reduces Ventricular Fibrillation Vulnerability.

Background The Purkinje network appears to play a pivotal role in the triggering as well as maintenance of ventricular fibrillation. Irreversible electroporation ( IRE ) using direct current has shown promise as a nonthermal ablation modality in the heart, but its ability to target and ablate the Purkinje tissue is undefined. Our aim was to investigate the potential for selective ablation of Purkinje/fascicular fibers using IRE . Methods and Results In an ex vivo Langendorff model of canine heart (n=8), direct current was delivered in a unipolar manner at various dosages from 750 to 2500 V, in 10 pulses with a 90-µs duration at a frequency of 1 Hz. The window of ventricular fibrillation vulnerability was assessed before and after delivery of electroporation energy using a shock on T-wave method. IRE consistently eradicated all Purkinje potentials at voltages between 750 and 2500 V (minimum field strength of 250-833 V/cm). The ventricular electrogram amplitude was only minimally reduced by ablation: 0.6±2.3 mV ( P=0.03). In 4 hearts after IRE delivery, ventricular fibrillation could not be reinduced. At baseline, the lower limit of vulnerability to ventricular fibrillation was 1.8±0.4 J, and the upper limit of vulnerability was 19.5±3.0 J. The window of vulnerability was 17.8±2.9 J. Delivery of electroporation energy significantly reduced the window of vulnerability to 5.7±2.9 J ( P=0.0003), with a postablation lower limit of vulnerability=7.3±2.63 J, and the upper limit of vulnerability=18.8±5.2 J. Conclusions Our study highlights that Purkinje tissue can be ablated with IRE without any evidence of underlying myocardial damage.

Feasibility of Performing Radiofrequency Catheter Ablation and Endomyocardial Biopsy in the Same Setting.

In patients with unexplained cardiomyopathy, electroanatomical mapping can identify abnormal tissue to target during electrophysiology-guided endomyocardial biopsy (EP-guided EMB). The objective of this study is to determine whether catheter ablation performed in the same setting as EP-guided EMB increases procedural risk. Sixty-seven patients (mean age 54.4 ± 13.8, 57% male) undergoing EP-guided EMB were included. Radiofrequency catheter ablation was performed in 17 patients (25%) for ventricular arrhythmias and in 2 (3%) for typical atrial flutter. Femoral arterial access was obtained in 90% ablation patients and 40% biopsy-only patients; vascular access complications were more common in the ablation group than in the EMB-only group (p = 0.02). There were no significant differences in rate of tricuspid regurgitation, thromboembolism, or pericardial effusion, whether procedural anticoagulation was used. In conclusion, catheter ablation and procedural anticoagulation can be combined with EP-guided EMB with an increased risk of vascular access complications, but no significant increase in intracardiac complications.

Mortality and Cerebrovascular Events After Heart Rhythm Disorder Management Procedures.

BACKGROUND: Recognition of rates and causes of hard, patient-centered outcomes of death and cerebrovascular events (CVEs) after heart rhythm disorder management (HRDM) procedures is an essential step for the development of quality improvement programs in electrophysiology laboratories. Our primary aim was to assess and characterize death and CVEs (stroke or transient ischemic attack) after HRDM procedures over a 17-year period. METHODS: We performed a retrospective cohort study of all patients undergoing HRDM procedures between January 2000 and November 2016 at the Mayo Clinic. Patients from all 3 tertiary academic centers (Rochester, Phoenix, and Jacksonville) were included in the study. All in-hospital deaths and CVEs after HRDM procedures were identified and were further characterized as directly or indirectly related to the HRDM procedure. Subgroup analysis of death and CVE rates was performed for ablation, device implantation, electrophysiology study, lead extraction, and defibrillation threshold testing procedures. RESULTS: A total of 48 913 patients (age, 65.7±6.6 years; 64% male) who underwent a total of 62 065 HRDM procedures were included in the study. The overall mortality and CVE rates in the cohort were 0.36% (95% confidence interval [CI], 0.31-0.42) and 0.12% (95% CI, 0.09-0.16), respectively. Patients undergoing lead extraction had the highest overall mortality rate at 1.9% (95% CI, 1.34-2.61) and CVE rate at 0.62% (95% CI, 0.32-1.07). Among patients undergoing HRDM procedures, 48% of deaths directly related to the HDRM procedure were among patients undergoing device implantation procedures. Overall, cardiac tamponade was the most frequent direct cause of death (40%), and infection was the most common indirect cause of death (29%). The overall 30-day mortality rate was 0.76%, with the highest being in lead extraction procedures (3.08%), followed by device implantation procedures (0.94%). CONCLUSIONS: Half of the deaths directly related to an HRDM procedure were among the patients undergoing device implantation procedures, with cardiac tamponade being the most common cause of death. This highlights the importance of the development of protocols for the quick identification and management of cardiac tamponade even in procedures typically believed to be lower risk such as device implantation.

Effect of Ventricular Arrhythmia Ablation in Patients With Heart Mate II Left Ventricular Assist Devices: An Evaluation of Ablation Therapy.

BACKGROUND: Patients with advanced heart failure (HF) are predisposed to ventricular arrhythmias (VAs), particularly following implantation of a left ventricular assist device (LVAD). There is minimal evidence for appropriate management strategies. OBJECTIVES: This study aimed to compare the burden of VA and response to ablation performed either before or following LVAD implantation. METHODS: We created a retrospective cohort of patients who underwent both VA ablation and Heart Mate II (Thoratec, Pleasanton, CA, USA) LVAD implantation at Mayo Clinic (Rochester, MN, USA). Patients were stratified based on whether they underwent VA ablation before (pre-LVAD) or after LVAD (post-LVAD) implantation. Descriptive analyses assessed 6-month arrhythmia burden in relation to LVAD implantation and VA ablation. RESULTS: A total of 9 patients underwent both LVAD implantation and VA ablation. There were 3 and 6 patients, respectively, in the pre-LVAD and post-LVAD cohorts. Among patients in the pre-LVAD cohort, the median number of VAs tended to increase after ablation (9 vs. 72) and decreased after LVAD implantation (72 vs. 63). Similarly among patients in the post-LVAD cohort, the median burden of VAs increased after LVAD implantation (1 vs. 22) and the median burden decreased after ablation (22 vs. 13). Two of 6 patients had substrate related to the LVAD inflow cannula site, while other substrate was not related directly to the cannula. CONCLUSIONS: In patients with progressive HF and LVAD implantation, ablation is associated with reduced VA rates. In LVAD patients, most VAs arise from substrate unrelated to the inflow cannula site.

Blood Pressure Responses to Endovascular Stimulation: A Potential Therapy for Autonomic Disorders With Vasodilatation.

BACKGROUND: We have previously shown that sympathetic ganglia stimulation via the renal vein rapidly increases blood pressure. This study further investigated the optimal target sites and effective energy levels for stimulation of the renal vasculatures and nearby sympathetic ganglia for rapid increase in blood pressure. METHODS: The pre-study protocol for endovascular stimulations included 2 minutes of stimulation (1-150 V and 10 pulses per second) and at least 2 minutes of rest during poststimulation. If blood pressure and/or heart rate were changed during the stimulation, time to return to baseline was allowed prior to the next stimulation. RESULTS: In 11 acute canine studies, we performed 85 renal artery, 30 renal vein, and 8 hepatic vasculature stimulations. The mean arterial pressure (MAP) rapidly increased during stimulation of renal artery (95 ± 18 mmHg vs. 103 ± 15 mmHg; P < 0.0001), renal vein (90 ± 16 mmHg vs. 102 ± 20 mmHg; P = 0.001), and hepatic vasculatures (74 ± 8 mmHg vs. 82 ± 11 mmHg; P = 0.04). Predictors of a significant increase in MAP were energy >10 V focused on the left renal artery, bilateral renal arteries, and bilateral renal veins (especially the mid segment). Overall, heart rate was unchanged, but muscle fasciculation was observed in 22.0% with an output >10 V (range 15-150 V). Analysis after excluding the stimulations that resulted in fasciculation yielded similar results to the main findings. CONCLUSIONS: Stimulation of intra-abdominal vasculatures promptly increased the MAP and thus may be a potential treatment option for hypotension in autonomic disorders. Predictors of optimal stimulation include energy delivery and the site of stimulation (for the renal vasculatures), which informs the design of subsequent research.

Endomyocardial biopsy-integrating electrode at the bioptome tip.

BACKGROUND: The addition of electroanatomic mapping to a standard echo-guided endomyocardial biopsy could identify areas of abnormal pathology and increase the diagnostic yield of the procedure. METHODS AND RESULTS: In this demonstration of a novel technique, a 45-year-old woman with clinical suspicion for cardiac sarcoidosis underwent right ventricular bipolar electroanatomical mapping with identification of areas of signal fractionation and low voltage. A bioptome, configured to record an electrogram from the tip, was then visualized on the three-dimensional electroanatomic mapping (3DEAM) system, and directed to these areas. The biopsy was assisted by the use of a steerable introducer sheath, and by recording unipolar and extended bipolar signals from the bioptome tip. A prominent change in the signal was detected by the electrode at the bioptome tip when the jaws closed on the endomyocardial tissue. Patient tolerated the procedure without complications, and the biopsied samples were appropriate for pathological analysis. CONCLUSIONS: Using existing technology, the 3DEAM, which integrates unipolar and bipolar signal from the bioptome tip, is feasible, and can be safely added to a standard echocardiographically guided endomyocardial biopsy. Future studies should investigate whether such a technique could increase the safety and diagnostic yield of endomyocardial biopsies in patients with suspected cardiomyopathies.

Electrogram guidance: a method to increase the precision and diagnostic yield of endomyocardial biopsy for suspected cardiac sarcoidosis and myocarditis.

OBJECTIVES: The aim of this study was to describe the method used to perform electrogram-guided EMB and correlate electrogram characteristics with pathological and clinical outcomes. BACKGROUND: Endomyocardial biopsy (EMB) is valuable in determining the underlying etiology of a cardiomyopathy. The sensitivity, however, for focal disorders, such as lymphocytic myocarditis and cardiac sarcoidosis (CS), is low. The sensitivity of routine fluoroscopically guided EMB is low. Abnormal intracardiac electrograms are seen at sites of myocardial disease. However, the exact value of electrogram-guided EMB is unknown. METHODS: We report 11 patients who underwent electrogram-guided EMB for evaluation of myocarditis and CS. RESULTS: Of 40 total biopsy specimens taken from 11 patients, 19 had electrogram voltage <5 mV, all of which resulted in histopathologic abnormality (100% specificity and positive predictive value). A voltage amplitude cutoff value of 5 mV had substantially higher sensitivity (70% vs. 26%) and negative predictive value (62%) than 1.5 mV. Abnormal electrogram appearance at biopsy site had good sensitivity (67%) and specificity (92%) in predicting abnormal myocardium. Normal signals with voltage >5 mV signified normal myocardium with no significant diagnostic yield. Biopsy results guided therapy in all patients, including 5 with active myocarditis or CS, all of whom subsequently received immunosuppressive therapy. There were no procedural complications. CONCLUSIONS: In patients with suspected myocarditis or CS, electrogram-guided EMB targeting sites with abnormal or low-amplitude electrograms may increase the diagnostic yield for detecting abnormal pathological findings.

Voltage mapping for delineating inexcitable dense scar in patients undergoing atrial fibrillation ablation: a new end point for enhancing pulmonary vein isolation.

BACKGROUND: Characterization of left atrial scar using bipolar voltage (BiV) mapping is not well defined. We have previously shown that the BiV range of 0.2-0.45 mV can identify chronic scar from prior pulmonary vein isolation (PVI). OBJECTIVE: This study sought to determine a BiV range that can identify atrial inexcitable dense scar (IDS) in patients acutely and chronically after PVI. METHODS: Thirty consecutive patients undergoing first time (n = 15) or redo (n = 15) PVI were included. A left atrial shell was created using electroanatomic mapping, and IDS was defined by inability to capture at an output of 10 mA and a pulse width of 2 ms in sinus rhythm, circumferentially at the edge of PVI-related scar (≤5 mm). At each pacing site, BiV amplitude and atrial capture were recorded. RESULTS: Overall, 837 pacing sites were assessed. BiV predicted IDS (receiver operating characteristic curve area 0.93 for first time PVI and 0.90 for redo PVI). In first time PVI, the best BiV value to predict IDS was 0.45 mV for the left pulmonary vein-left atrial appendage (LAA-LPV) ridge (sensitivity 0.98; specificity 1.0) and 0.2 mV for other localizations (sensitivity 0.91; specificity 0.86). In redo PVI, the best BiV value to predict IDS was 0.2 mV for the LAA-LPV ridge (sensitivity 0.77; specificity 1.0) and 0.15 mV for other localizations (sensitivity 0.81; specificity 0.82). CONCLUSION: BiV reproducibly identifies acute and chronic IDS using a cutoff value of 0.2 mV (0.45 mV for the LAA-LPV ridge) in patients undergoing first time PVI and 0.15 mV (0.2 mV for the LAA-LPV ridge) in patients undergoing redo PVI. IDS thus identified may be a rigorous tool for validating PVI.

Characterization of trans-septal activation during septal pacing: criteria for identification of intramural ventricular tachycardia substrate in nonischemic cardiomyopathy.

BACKGROUND: Identification of intramural basal-septal ventricular tachycardia (VT) substrate is challenging in nonischemic cardiomyopathy. We sought to (1) characterize normal/abnormal trans-septal right ventricular (RV) to left ventricular activation; (2) assess the effect of opposite RV pacing on left ventricular septal bipolar electrograms (EGMs); and (3) establish criteria for the identification of intramural septal VT substrate. METHODS AND RESULTS: Endocardial activation mapping and local EGM assessment of the left interventricular septum was performed during RV basal septal pacing in 40 patients undergoing VT ablation with no evidence of septal scar (group 1, n=14) and with septal scar (group 2, n=26) defined by low septal unipolar voltage (<8.3 mV) and delayed enhancement on cardiac MRI with/without abnormal bipolar voltage (<1.5 mV) in sinus rhythm. Left ventricular trans-septal activation time was prolonged in Group 2 compared with Group 1 (55.3±33.0 versus 25.7±8.8 ms; P=0.003). In 6 group 2 patients, left ventricular septal breakthrough was displaced to the scar border. During RV pacing, group 2 had fractionated (8.8%), late (2.8%), and split (5.7%) EGMs not seen in group 1. Trans-septal activation >40 ms (sensitivity 60%, specificity 100%; P<0.001) and EGM duration >95 ms during pacing (sensitivity 22%, specificity 91%; P<0.001) identified septal scar (13/26 pts). CONCLUSIONS: In patients with nonischemic cardiomyopathy, VT and septal scar, delayed transmural conduction time (>40 ms) and fractionated, late, split, and wide (>95 ms) bipolar EGMs during RV basal pacing identify intramural VT substrate. In select cases, the basal septum appears compartmentalized as the stimulated wavefront is rerouted to the scar border.