P-wave alternans rebound following pulmonary vein isolation predicts atrial arrhythmia recurrence.

INTRODUCTION: Numerous P-wave indices have been explored as biomarkers to assess atrial fibrillation (AF) risk and the impact of therapy with variable success. OBJECTIVE: We investigated the utility of P-wave alternans (PWA) to track the effects of pulmonary vein isolation (PVI) and to predict atrial arrhythmia recurrence. METHODS: This medical records study included patients who underwent PVI for AF ablation at our institution, along with 20 control subjects without AF or overt cardiovascular disease. PWA was assessed using novel artificial intelligence-enabled modified moving average (AI-MMA) algorithms. PWA was monitored from the 12-lead ECG at ~1 h before and ~16 h after PVI (n = 45) and at the 4- to 17-week clinically indicated follow-up visit (n = 30). The arrhythmia follow-up period was 955 ± 112 days. RESULTS: PVI acutely reduced PWA by 48%-63% (p < .05) to control ranges in leads II, III, aVF, the leads with the greatest sensitivity in monitoring PWA. Pre-ablation PWA was ~6 µV and decreased to ~3 µV following ablation. Patients who exhibited a rebound in PWA to pre-ablation levels at 4- to 17-week follow-up (p < .01) experienced recurrent atrial arrhythmias, whereas patients whose PWA remained reduced (p = .85) did not, resulting in a significant difference (p < .001) at follow-up. The AUC for PWA's prediction of first recurrence of atrial arrhythmia was 0.81 (p < .01) with 88% sensitivity and 82% specificity. Kaplan-Meier analysis estimated atrial arrhythmia-free survival (p < .01) with an adjusted hazard ratio of 3.4 (95% CI: 1.47-5.24, p < .02). CONCLUSION: A rebound in PWA to pre-ablation levels detected by AI-MMA in the 12-lead ECG at standard clinical follow-up predicts atrial arrhythmia recurrence.

Competing risks of monomorphic vs. non-monomorphic ventricular arrhythmias in primary prevention implantable cardioverter-defibrillator recipients: Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study.

AIMS: Ablation of monomorphic ventricular tachycardia (MMVT) has been shown to reduce shock frequency and improve survival. We aimed to compare cause-specific risk factors for MMVT and polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF) and to develop predictive models. METHODS AND RESULTS: The multicentre retrospective cohort study included 2668 patients (age 63.1 ± 13.0 years; 23% female; 78% white; 43% non-ischaemic cardiomyopathy; left ventricular ejection fraction 28.2 ± 11.1%). Cox models were adjusted for demographic characteristics, heart failure severity and treatment, device programming, and electrocardiogram metrics. Global electrical heterogeneity was measured by spatial QRS-T angle (QRSTa), spatial ventricular gradient elevation (SVGel), azimuth, magnitude (SVGmag), and sum absolute QRST integral (SAIQRST). We compared the out-of-sample performance of the lasso and elastic net for Cox proportional hazards and the Fine-Gray competing risk model. During a median follow-up of 4 years, 359 patients experienced their first sustained MMVT with appropriate implantable cardioverter-defibrillator (ICD) therapy, and 129 patients had their first PVT/VF with appropriate ICD shock. The risk of MMVT was associated with wider QRSTa [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.01-1.34], larger SVGel (HR 1.17; 95% CI 1.05-1.30), and smaller SVGmag (HR 0.74; 95% CI 0.63-0.86) and SAIQRST (HR 0.84; 95% CI 0.71-0.99). The best-performing 3-year competing risk Fine-Gray model for MMVT [time-dependent area under the receiver operating characteristic curve (ROC(t)AUC) 0.728; 95% CI 0.668-0.788] identified high-risk (> 50%) patients with 75% sensitivity and 65% specificity, and PVT/VF prediction model had ROC(t)AUC 0.915 (95% CI 0.868-0.962), both satisfactory calibration. CONCLUSION: We developed and validated models to predict the competing risks of MMVT or PVT/VF that could inform procedural planning and future randomized controlled trials of prophylactic ventricular tachycardia ablation. CLINICAL TRIAL REGISTRATION: URL:www.clinicaltrials.gov Unique identifier:NCT03210883.

Limits of the spatial ventricular gradient and QRST angles in patients with normal electrocardiograms and no known cardiovascular disease stratified by age, sex, and race.

INTRODUCTION: Measurement of the spatial ventricular gradient (SVG), spatial QRST angles, and other vectorcardiographic measures of myocardial electrical heterogeneity have emerged as novel risk stratification methods for sudden cardiac death and other adverse cardiovascular events. Prior studies of normal limits of these measurements included primarily young, healthy, White volunteers, but normal limits in older patients are unknown. The influence of race and body mass index (BMI) on these measurements is also unclear. METHODS: Normal 12-lead electrocardiograms (ECGs) from a single center were identified. Patients with abnormal cardiovascular, pulmonary, or renal history (assessed by International Classification of Disease [ICD-9/ICD-10] codes) or abnormal cardiovascular imaging were excluded. The SVG and QRST angles were measured and stratified by age, sex, and race. Multivariable linear regression was used to assess the influence of age, BMI, and heart rate (HR) on these measurements. RESULTS: Among 3292 patients, observed ranges of SVG and QRST angles (peak and mean) differed significantly based on sex, age, and race. Sex differences attenuated with increasing age. Men tended to have larger SVG magnitude (60.4 [46.1-77.8] vs. 52.5 [41.3-65.8] mv*ms, p < .0001) and elevation, and more anterior/negative SVG azimuth (-14.8 [-25.1 to -4.3] vs. 1.3 [-9.8 to 10.5] deg, p < .0001) compared to women. Men also had wider QRST angles. Observed ranges varied significantly with BMI and HR. SVG and QRST angle measurements were robust to different filtering bandwidths and moderate fiducial point annotation errors, but were heavily affected by changes in baseline correction. CONCLUSIONS: Age, sex, race, BMI, and HR significantly affect the range of SVG and QRST angles in patients with normal ECGs and no known cardiovascular disease, and should be accounted for in future studies. An online calculator for prediction of these "normal limits" given demographics is provided at https://bivectors.github.io/gehcalc/.

Individuals with chronic epilepsy have elevated P-wave heterogeneity comparable to patients with atrial fibrillation.

OBJECTIVE: Identification of epilepsy patients with elevated risk for atrial fibrillation (AF) is critical given the heightened morbidity and premature mortality associated with this arrhythmia. Epilepsy is a worldwide health problem affecting nearly 3.4 million people in the United States alone. The potential for increased risk for AF in patients with epilepsy is not well appreciated, despite recent evidence from a national survey of 1.4 million hospitalizations indicating that AF is the most common arrhythmia in people with epilepsy. METHODS: We analyzed inter-lead heterogeneity of P-wave morphology, a marker reflecting arrhythmogenic nonuniformities of activation/conduction in atrial tissue. The study groups consisted of 96 patients with epilepsy and 44 consecutive patients with AF in sinus rhythm before clinically indicated ablation. Individuals without cardiovascular or neurological conditions (n = 77) were also assessed. We calculated P-wave heterogeneity (PWH) by second central moment analysis of simultaneous beats from leads II, III, and aVR ("atrial dedicated leads") from standard 12-lead electrocardiography (ECG) recordings from admission day to the epilepsy monitoring unit (EMU). RESULTS: Female patients composed 62.5%, 59.6%, and 57.1% of the epilepsy, AF, and control subjects, respectively. The AF cohort was older (66 ± 1.1 years) than the epilepsy group (44 ± 1.8 years, p < .001). The level of PWH was greater in the epilepsy group than in the control group (67 ± 2.6 vs. 57 ± 2.5 µV, p = .046) and reached levels observed in AF patients (67 ± 2.6 vs. 68 ± 4.9 µV, p = .99). In multiple linear regression analysis, PWH levels in individuals with epilepsy were mainly correlated with the PR interval and could be related to sympathetic tone. Epilepsy remained associated with PWH after adjustments for cardiac risk factors, age, and sex. SIGNIFICANCE: Patients with chronic epilepsy have increased PWH comparable to levels observed in patients with AF, while being ~20 years younger, suggesting an acceleration in structural change and/or cardiac electrical instability. These observations are consistent with emerging evidence of an "epileptic heart" condition.

The spatial ventricular gradient is associated with adverse outcomes in acute pulmonary embolism.

BACKGROUND: The spatial ventricular gradient (SVG) is a vectorcardiographic measurement that reflects cardiac loading conditions via electromechanical coupling. OBJECTIVES: We hypothesized that the SVG is correlated with right ventricular (RV) strain and is prognostic of adverse events in patients with acute pulmonary embolism (PE). METHODS: Retrospective, single-center study of patients with acute PE. Electrocardiogram (ECG), imaging, and outcome data were obtained. SVG components were regressed on tricuspid annular plane systolic excursion (TAPSE), qualitative RV dysfunction, and RV/left ventricular (LV) ratio. Odds of adverse outcomes (30-day mortality, vasopressor requirement, or advanced therapy) after PE were regressed on demographics, RV/LV ratios, traditional ECG signs of RV dysfunction, and SVG components using a logit model. RESULTS: ECGs from 317 patients (48% male, age 63.1 ± 16.6 years) with acute PE were analyzed; 36 patients (11.4%) experienced an adverse event. Worse RV hypokinesis, larger RV/LV ratio, and smaller TAPSE were associated with smaller SVG X and Y components, larger SVG Z components, and smaller SVG vector magnitude (p < .001 for all). In multivariable logistic regression, odds of adverse events after PE decreased with increasing SVG magnitude and TAPSE (OR 0.32 and 0.54 per standard deviation increase; p = .03 and p = .004, respectively). Receiver operating characteristic (ROC) analysis showed that, when combined with imaging, replacing traditional ECG criteria with the SVG significantly improved the area under the ROC from 0.70 to 0.77 (p = .01). CONCLUSION: The SVG is correlated with RV dysfunction and adverse outcomes in acute PE and has a better prognostic value than traditional ECG markers.

Risk Stratification for Sudden Cardiac Death After Myocardial Infarction.

Sudden cardiac death (SCD) accounts for ∼50% of mortality after myocardial infarction (MI). Most SCDs result from ventricular tachyarrhythmias, and the tachycardias that precipitate cardiac arrest result from multiple mechanisms. As a result, it is highly unlikely that any single test will identify all patients at risk for SCD. Current guidelines for use of implantable cardioverter-defibrillators (ICDs) to prevent SCD are based primarily on measurement of left ventricular ejection fraction (LVEF). Although reduced LVEF is associated with increased total cardiac mortality after MI, the focus of current guidelines on LVEF omits ∼50% of patients who die suddenly. In addition, there is no evidence of a mechanistic link between reduced LVEF and arrhythmias. Thus, LVEF is neither sensitive nor specific as a tool for post-MI risk stratification. Newer tests to screen for predisposition to ventricular arrhythmias and SCD examine abnormalities of ventricular repolarization, autonomic nervous system function, and electrical heterogeneity. These tests, as well as older methods such as programmed stimulation, the signal-averaged electrocardiogram, and spontaneous ventricular ectopy, do not perform well in patients with LVEF ≤30%. Recent observational studies suggest, however, that these tests may have greater utility in patients with LVEF >30%. Because SCD results from multiple mechanisms, it is likely that combinations of risk factors will prove more precise for risk stratification. Prospective trials that evaluate the performance of risk stratification schema to determine ICD use are necessary for cost-effective reduction of the incidence of SCD after MI.

Association between the Charlson comorbidity index and outcomes after implantable cardioverter defibrillator generator replacement.

BACKGROUND: Recipients of implantable cardioverter defibrillator (ICD) generator replacement with multiple medical comorbidities may be at higher risk of adverse outcomes that attenuate the benefit of ICD replacement. The aim of this investigation was to study the association between the Charlson comorbidity index (CCI) and outcomes after ICD generator replacement. METHODS: All patients undergoing first ICD generator replacement at Mayo Clinic, Rochester and Beth Israel Deaconess Medical Center, Boston between 2001 and 2011 were identified. Outcomes included: (a) all-cause mortality, (b) appropriate ICD therapy, and (c) death prior to appropriate therapy. Multivariable Cox regression analysis was performed to assess association between CCI and outcomes. RESULTS: We identified 1421 patients with mean age of 69.6 ± 12.1 years, 81% male and median (range) CCI of 3 (0-18). During a mean follow-up of 3.9 ± 3 years, 52% of patients died, 30.6% experienced an appropriate therapy, and 23.6% died without experiencing an appropriate therapy. In multivariable analysis, higher CCI score was associated with increased all-cause mortality (Hazard ratio, HR 1.10 [1.06-1.13] per 1 point increase in CCI, P < .001), death without prior appropriate therapy (HR 1.11 [1.07-1.15], P < .0001), but not associated with appropriate therapy (HR 1.01 [0.97-1.05], P = .53). Patients with CCI ≥5 had an annual risk of death of 12.2% compared to 8.7% annual rate of appropriate therapy. CONCLUSIONS: CCI is predictive of mortality following ICD generator replacement. The benefit of ICD replacement in patients with CCI score ≥5 should be investigated in prospective studies.

Clinical and regulatory considerations for novel electrophysiology mapping systems: Lessons from FIRM.

Atrial fibrillation (AF) presents a growing clinical and public health burden for which better rhythm control therapies are needed. Focal impulse and rotor mapping (FIRM), currently marketed as a part of the Topera Rotor Mapping system (Abbott Laboratories, Austin, TX, USA), represents a potentially transformational approach to guide the invasive treatment of AF. However, many years after its initial marketing clearance, the clinical utility of this technology remains uncertain. In this article, we review the scientific rationale for this novel approach to AF ablation, evaluate the current clinical evidence for FIRM-guided ablation, and characterize its premarket regulatory assessment. Lessons for clinicians considering adoption of newly marketed mapping systems are presented.

Global Electric Heterogeneity Risk Score for Prediction of Sudden Cardiac Death in the General Population: The Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies.

BACKGROUND: Asymptomatic individuals account for the majority of sudden cardiac deaths (SCDs). Development of effective, low-cost, and noninvasive SCD risk stratification tools is necessary. METHODS AND RESULTS: Participants from the Atherosclerosis Risk in Communities study and Cardiovascular Health Study (n=20 177; age, 59.3±10.1 years; age range, 44-100 years; 56% female; 77% white) were followed up for 14.0 years (median). Five ECG markers of global electric heterogeneity (GEH; sum absolute QRST integral, spatial QRST angle, spatial ventricular gradient [SVG] magnitude, SVG elevation, and SVG azimuth) were measured on standard 12-lead ECGs. Cox proportional hazards and competing risks models evaluated associations between GEH electrocardiographic parameters and SCD. An SCD competing risks score was derived from demographics, comorbidities, and GEH parameters. SCD incidence was 1.86 per 1000 person-years. After multivariable adjustment, baseline GEH parameters and large increases in GEH parameters over time were independently associated with SCD. Final SCD risk scores included age, sex, race, diabetes mellitus, hypertension, coronary heart disease, stroke, and GEH parameters as continuous variables. When GEH parameters were added to clinical/demographic factors, the C statistic increased from 0.777 to 0.790 (P=0.008), the risk score classified 10-year SCD risk as high (>5%) in 7.2% of participants, 10% of SCD victims were appropriately reclassified into a high-risk category, and only 1.4% of SCD victims were inappropriately reclassified from high to intermediate risk. The net reclassification index was 18.3%. CONCLUSIONS: Abnormal electrophysiological substrate quantified by GEH parameters is independently associated with SCD in the general population. The addition of GEH parameters to clinical characteristics improves SCD risk prediction.

Targeted Anticoagulation for Atrial Fibrillation Guided by Continuous Rhythm Assessment With an Insertable Cardiac Monitor: The Rhythm Evaluation for Anticoagulation With Continuous Monitoring (REACT.COM) Pilot Study.

INTRODUCTION: Chronic anticoagulation is recommended for patients with AF and additional stroke risk factors, even during long periods of sinus rhythm. Continuous rhythm assessment with an insertable cardiac monitor (ICM) and use of rapid onset novel oral anticoagulants (NOACs) allow for targeted anticoagulation only around an AF episode, potentially reducing bleeding complications without compromising stroke risk. METHODS: This multicenter, single-arm study enrolled patients on NOAC with nonpermanent AF and CHADS2 score 1 or 2. After a 60-day run-in with no AF episodes ≥ 1 hour, NOACs were discontinued but reinitiated for 30 days following any AF episode ≥ 1 hour diagnosed through daily ICM transmissions. Major endpoints included time on NOAC, stroke, and bleeding. RESULTS: Among 59 enrollees, 75% were male, age 67 ± 8 years, 76% paroxysmal AF, 69% had prior AF ablation, and mean CHADS2 score 1.3 ± 0.5. Over 466 ± 131 mean days of follow-up there were 24,004 ICM transmissions with a compliance rate of 98.7%. A total of 35 AF episodes ≥ 1 hour occurred in 18 (31%) patients, resulting in a total time on NOAC of 1,472 days. This represents a 94% reduction in the time on NOAC compared to chronic anticoagulation. There were three traumatic bleeds (all on aspirin), three potential transient ischemic attacks (all on aspirin with CHADS2 score of 1), and no strokes or deaths. CONCLUSIONS: A targeted strategy of ICM-guided intermittent NOAC administration is feasible. A large-scale trial is necessary to evaluate the safety of this approach.

Incidence and risk factors for symptomatic heart failure after catheter ablation of atrial fibrillation and atrial flutter.

AIMS: To determine the incidence and risk factors for development of symptomatic heart failure (HF) following catheter ablation for atrial fibrillation (AF) and atrial flutter. METHODS AND RESULTS: We prospectively enrolled consecutive patients undergoing pulmonary vein isolation (PVI) or cavotricuspid isthmus (CTI) ablation between November 2013 and June 2014. Post-discharge symptoms were assessed via telephone follow-up and clinic visits. The primary outcome was symptomatic HF requiring treatment with new/increased diuretic dosing. Secondary outcomes were prolonged index hospitalization and readmission for HF ≤30 days. Univariate and multivariable logistic regressions were used to assess the relationship between patient/procedural characteristic and post-ablation HF. Among 111 PVI patients [median age 62.0 years; left ventricular ejection fraction (LVEF) 55%], 29 patients (26.1%) developed symptomatic HF, 6 patients (5.4%) required prolonged index hospitalization, and 8 patients (7.2%) were readmitted for HF. In univariate analyses, persistent AF [odds ratio (OR) 2.97, P = 0.02], AF at start of the procedure (OR 2.99, P = 0.01), additional ablation lines (OR 11.07, P < 0.0001), and final left atrial pressure (OR 1.10 per 1 mmHg increase, P = 0.02) were associated with HF development. Peri-procedural diuresis, net fluid balance, and LVEF were not correlated. In multivariable analyses, only additional ablation lines (ORadj 9.17, P = 0.007) were independently associated with post-ablation HF. Six patients (16.7%) developed HF after CTI ablation. CONCLUSION: A 26.1% of patients undergoing PVI and 16.7% of patients undergoing CTI ablation developed symptomatic HF when prospectively and uniformly assessed. 12.6% of patients experienced prolonged index hospitalizations or readmission for management of HF within 1 week after PVI. Improved understanding of risk factors for post-ablation HF may be critical in developing strategies to address during AF ablation.

Global electrical heterogeneity: A review of the spatial ventricular gradient.

The ventricular gradient, an electrocardiographic concept calculated by integrating the area under the QRS complex and T-wave, represents the degree and direction of myocardial electrical heterogeneity. Although the concept of the ventricular gradient was first introduced in the 1930s, it has not yet found a place in routine electrocardiography. In the modern era, it is relatively simple to calculate the ventricular gradient in three dimensions (the spatial ventricular gradient (SVG)), and there is now renewed interest in using the SVG as a tool for risk stratification of ventricular arrhythmias and sudden cardiac death. This manuscript will review the history of the ventricular gradient, describe its electrophysiological meaning and significance, and discuss its clinical utility.

Electrocardiographic predictors of mortality and sudden cardiac death in patients with end stage renal disease on hemodialysis.

Patients with end stage renal disease (ESRD) on hemodialysis experience a high incidence of cardiovascular mortality, and sudden cardiac death (SCD) accounts for approximately 25% of all deaths in this patient population. Despite this high risk of SCD, many non-invasive SCD risk stratification tools that are frequently applied to other patient populations (such as those with prior myocardial infarction and reduced left ventricular systolic function) may be less useful markers of increased SCD risk in ESRD. Improved SCD risk stratification tools for use specifically in patients on hemodialysis are therefore necessary to optimally target use of primary prevention interventions aimed at decreasing SCD incidence. Electrocardiography is an effective, non-invasive SCD risk stratification tool in hemodialysis patients. This article reviews data supporting the association between various ECG parameters (QT interval, spatial QRS-T angle, signal averaged ECG, heart rate variability, and T-wave alternans) and mortality/SCD in the dialysis population. Despite the association between abnormal ECG parameters and SCD, it remains unclear if these abnormal parameters (such as prolonged QT interval) are mechanistically related to SCD and/or ventricular arrhythmias, or if they are simply markers for more severe cardiac disease, such as left ventricular hypertrophy, that may independently predispose to SCD. Current obstacles that impair widespread implementation of ECG risk stratification in the hemodialysis population are also discussed.

Risk stratification for sudden cardiac death in North America - current perspectives.

Sudden cardiac death (SCD) accounts for approximately 360,000 deaths annually in the United States, and is the cause of half of all cardiovascular deaths. In patients with severely depressed left ventricular ejection fraction (LVEF), implantable cardioverter-defibrillators (ICDs) have been shown to significantly reduce total mortality, but many factors beyond LVEF influence the relative benefit afforded by ICD implantation. In fact, among patients with prior myocardial infarction, approximately half of all SCDs occur in patients without severe LV dysfunction, and in analyses of large ICD trials, certain patient subgroups derive no benefit to ICD implantation despite having low LVEF, often due to competing non-arrhythmic mortality. Improved risk stratification tools to help select patients who are likely to derive the most benefit from ICD implantation are therefore needed. This manuscript will review studies evaluating use of ICDs in patients with mild LV systolic dysfunction and LVEF >35%, currently available ICD risk stratification models, and the rationale for designing a cohort study to prospectively validate use of an ICD risk stratification score.

Quantitative Assessment of Vectorcardiographic Loop Morphology.

Vectorcardiography (VCG), developed 100years ago, characterizes clinically important electrophysiological properties of the heart. In this study, VCG QRS loop roundness, planarity, thickness, rotational angle, and dihedral angle were measured in 81 healthy control subjects (39.0±14.2y; 51.8% male; 94% white), and 8 patients with infarct-cardiomyopathy and sustained monomorphic ventricular tachycardia (VT) (68.0±7.8y, 37.5% male). The angle between two consecutive QRS vectors was defined as the rotational angle, while dihedral angle quantified planar alteration over the QRS loop. In VT subjects, planarity index decreased (0.63±0.22 vs. 0.88±0.10; P=0.014), and dihedral angle was significantly more variable (variance of dihedral angle, median (IQR): 897(575-1450) vs. 542(343-773); P=0.029; rMSSD: 47.7±12.7 vs. 35.1±13.1; P=0.027). Abnormal electrophysiological substrate in VT patients is characterized by the appearance of QRS loop folding, likely due to local conduction block. The presence of fragmented QRS complexes on the 12-lead ECG had low sensitivity (31%) for detecting QRS loop folding on the VCG.

Influence of renal function on mortality and ventricular arrhythmias in patients undergoing first implantable cardioverter-defibrillator generator replacement.

BACKGROUND: Impaired renal function is associated with increased mortality among patients with implantable cardioverter-defibrillators (ICDs). The relationship between renal function at time of ICD generator replacement and subsequent appropriate ICD therapies is not known. METHODS AND RESULTS: We identified 441 patients who underwent first ICD generator replacement between 2000 and 2011 and had serum creatinine measured within 30 days of their procedure. Patients were divided into tertiles based on estimated glomerular filtration rate (eGFR). Adjusted Cox proportional hazard and competing risk models were used to assess relationships between eGFR and subsequent mortality and appropriate ICD therapy. Median eGFR was 37.6, 59.3, and 84.8 mL/min/1.73 m(2) for tertiles 1-3, respectively. Five-year Kaplan-Meier survival probability was 34.8%, 61.4%, and 84.5% for tertiles 1-3, respectively (P < 0.001). After multivariable adjustment, compared to tertile 3, worse eGFR tertile was associated with increased mortality (HR 2.84, 95% CI [1.36-5.94] for tertile 2; HR 3.84, 95% CI [1.81-8.12] for tertile 1). At 5 years, 57.0%, 58.1%, and 60.2% of patients remained free of appropriate ICD therapy in tertiles 1-3, respectively (P = 0.82). After adjustment, eGFR tertile was not associated with future appropriate ICD therapy. Results were unchanged in an adjusted competing risk model accounting for death. CONCLUSIONS: At time of first ICD generator replacement, lower eGFR is associated with higher mortality, but not with appropriate ICD therapies. The poorer survival of ICD patients with reduced eGFR does not appear to be influenced by arrhythmia status, and there is no clear proarrhythmic effect of renal dysfunction, even after accounting for the competing risk of death.

Effect of ranolazine on atrial fibrillation in patients with non-ST elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 trial.

AIMS: To determine the effect of ranolazine, an anti-ischaemic agent with anti-arrhythmic properties, on the overall burden of atrial fibrillation (AF) in acute coronary syndromes (ACS) and determine whether ranolazine reduces the long-term incidence of clinical AF after ACS. METHODS AND RESULTS: MERLIN-TIMI 36 randomized patients with non-ST elevation ACS to ranolazine or placebo. Atrial fibrillation episodes detected on continuous electrocardiogram (cECG) monitoring were reviewed in 6351 patients (97% of trial). Atrial fibrillation burden was categorized according to the time in AF: clinically insignificant AF (<0.01% of time), paroxysmal AF (>0.01-98%), or predominantly persistent AF (>98%). Clinical AF events were identified through adverse event reporting for a median 1-year follow-up. Overall, patients assigned to ranolazine had a trend towards fewer episodes of AF [75 (2.4%) vs. 55 (1.7%) patients, P = 0.08] detected on cECG during the first 7 days after randomization. The pattern of new-onset AF differed between ranolazine vs. placebo: clinically insignificant AF (five patients in ranolazine vs. seven in placebo), paroxysmal AF (18 vs. 48 patients), and predominantly chronic AF (28 vs. 20 patients, three-way P < 0.01). Among patients with a paroxysmal AF pattern, the overall burden was lower with ranolazine than with placebo (median 4.4 vs.16.1%, P = 0.015). Over the median 1-year follow-up, fewer patients treated with ranolazine experienced an AF event compared with placebo (2.9 vs. 4.1%, RR 0.71, P = 0.01). CONCLUSION: Ranolazine, an anti-anginal agent with electrophysiological effects, may reduce the frequency of paroxysmal AF in patients with non-ST elevation ACS with a pattern of lower overall AF burden in this group. Ranolazine reduced the overall 1-year incidence of clinical AF events. These atrial-specific anti-arrhythmic properties of ranolazine may be of clinical interest and warrant additional investigation. CLINICAL TRIAL REGISTRATION: NCT00099788.

Targeting Wavefront Discontinuity Lines for Scar-Related Ventricular Tachycardia Ablation: A Novel Functional Substrate Ablation Approach.

BACKGROUND: The boundaries of critical isthmuses for re-entrant ventricular tachycardia (VT) are formed by wave-front discontinuities (fixed lines of block, slow propagation, and rotational propagation) seen during baseline rhythm. It is unknown whether wavefront discontinuities can be automatically identified and targeted for ablation using electroanatomic mapping systems. OBJECTIVES: The purpose of this study was to assess the electrophysiologic characteristics of automatically projected wavefront discontinuity lines (WADLs) and outcomes of an ablation strategy targeting WADLs in a mixed cohort of VT patients. METHODS: Late activation substrate maps were analyzed from 1 or more baseline rhythm wavefronts. WADLs were identified using the Carto Extended Early Meets Late module. Number, total length, and distance to critical VT sites were measured. VT recurrence and VT-free survival were followed. RESULTS: In total, 49 patients underwent 52 ablations with 71 unique substrate maps analyzed (18.8% epicardial; 62.0% right ventricular paced, 28.2% sinus rhythm, 9.9% left ventricular paced). A total of 28 VT critical sites were identified in 24 patients. WADLs were present in 49 of 71 (69.0%) maps. WADLs were present regardless of cardiomyopathy etiology, mapping wavefront, or surface. At a WADL threshold of 30%, 73.9% of critical VT sites were in close proximity (≤15 mm) to a WADL. VT-free survival was 62% at 1 year, with a competing risk model estimating a 1-year risk of VT recurrence of 23%. CONCLUSIONS: WADLs can be automatically projected in a majority of patients in a mixed cohort of cardiomyopathy etiology, mapped wavefronts, and myocardial surfaces mapped. Targeting WADLs results in low rate of VT recurrence at 1 year.

Recovery and safety with prolonged high-frequency jet ventilation for catheter ablation of atrial fibrillation: A hospital registry study from a New England healthcare network.

STUDY OBJECTIVE: To investigate post-procedural recovery as well as peri-procedural respiratory and hemodynamic safety parameters with prolonged use of high-frequency jet ventilation (HFJV) versus conventional ventilation in patients undergoing catheter ablation for atrial fibrillation. DESIGN: Hospital registry study. SETTING: Tertiary academic teaching hospital in New England. PATIENTS: 1822 patients aged 18 years and older undergoing catheter ablation between January 2013 and June 2020. INTERVENTIONS: HFJV versus conventional mechanical ventilation. MEASUREMENTS: The primary outcome was post-anesthesia care unit (PACU) length of stay. In secondary analyses we assessed the effect of HFJV on intra-procedural hypoxemia, defined as the occurrence of peripheral hemoglobin oxygen saturation (SpO2) <90%, post-procedural respiratory complications (PRC) as well as intra-procedural hypocarbia and hypotension. Multivariable negative binomial and logistic regression analyses, adjusted for patient and procedural characteristics, were applied. MAIN RESULTS: 1157 patients (63%) received HFJV for a median (interquartile range [IQR]) duration of 307 (253-360) minutes. The median (IQR) length of stay in the PACU was 244 (172-370) minutes in patients who underwent ablation with conventional mechanical ventilation and 226 (163-361) minutes in patients receiving HFJV. In adjusted analyses, patients undergoing HFJV had a longer PACU length of stay (adjusted absolute difference: 37.7 min; 95% confidence interval [CI] 9.7-65.8; p = 0.008). There was a higher risk of intra-procedural hypocarbia (adjusted odds ratio [ORadj] 5.90; 95%CI 2.63-13.23; p < 0.001) and hypotension (ORadj 1.88; 95%CI 1.31-2.72; p = 0.001) in patients undergoing HFJV. No association was found between the use of HFJV and intra-procedural hypoxemia or PRC (p = 0.51, and p = 0.97, respectively). CONCLUSION: After confounder adjustment, HFJV for catheter ablation procedures for treatment of atrial fibrillation was associated with a longer length of stay in the PACU. It was further associated with an increased risk of intra-procedural abnormalities including abnormal carbon dioxide homeostasis, as well as intra-procedural arterial hypotension.

Deep neural networks detect regional wall motion abnormalities and preclinical cardiovascular disease from 12-lead ECGs.

Background: Identifying regional wall motion abnormalities (RWMAs) is critical for diagnosing and risk stratifying patients with cardiovascular disease, particularly ischemic heart disease. We hypothesized that a deep neural network could accurately identify patients with regional wall motion abnormalities from a readily available standard 12-lead electrocardiogram (ECG). Methods: This observational, retrospective study included patients who were treated at Beth Israel Deaconess Medical Center and had an ECG and echocardiogram performed within 14 days of each other between 2008 and 2019. We trained a convolutional neural network to detect the presence of RWMAs, qualitative global right ventricular (RV) hypokinesis, and varying degrees of left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤50%, LVEF ≤40%, and LVEF ≤35%) identified by echocardiography, using ECG data alone. Patients were randomly split into development (80%) and test sets (20%). Model performance was assessed using area under the receiver operating characteristic curve (AUC). Cox proportional hazard models adjusted for age and sex were performed to estimate the risk of future acute coronary events. Results: The development set consisted of 19,837 patients (mean age 66.7±16.4; 46.7% female) and the test set comprised of 4,953 patients (mean age 67.5±15.8 years; 46.5% female). On the test dataset, the model accurately identified the presence of RWMA, RV hypokinesis, LVEF ≤50%, LVEF ≤40%, and LVEF ≤35% with AUCs of 0.87 (95% CI 0.858-0.882), 0.888 (95% CI 0.878-0.899), 0.923 (95% CI 0.914-0.933), 0.93 (95% CI 0.921-0.939), and 0.876 (95% CI 0.858-0.896), respectively. Among patients with normal biventricular function at the time of the index ECG, those classified as having RMWA by the model were 3 times the risk (age- and sex-adjusted hazard ratio, 2.8; 95% CI 1.9-3.9) for future acute coronary events compared to those classified as negative. Conclusions: We demonstrate that a deep neural network can help identify regional wall motion abnormalities and reduced LV function from a 12-lead ECG and could potentially be used as a screening tool for triaging patients who need either initial or repeat echocardiographic imaging.