P-Wave Duration/Amplitude Ratio Quantifies Atrial Low-Voltage Area and Predicts Atrial Arrhythmia Recurrence After Pulmonary Vein Isolation.

BACKGROUND: Atrial low-voltage areas (LVAs) in patients with atrial fibrillation increase the risk of atrial arrhythmia (AA) recurrence after pulmonary vein isolation (PVI). Contemporary LVA prediction scores (DR-FLASH, APPLE) do not include P-wave metrics. We aimed to evaluate the utility of P-wave duration/amplitude ratio (PWR) in quantifying LVA and predicting AA recurrence after PVI. METHODS: In 65 patients undergoing first-time PVI, 12-lead ECGs were recorded during sinus rhythm. PWR was calculated as the ratio between the longest P-wave duration and P-wave amplitude in lead I. High-resolution biatrial voltage maps were collected and LVAs included bipolar electrogram amplitudes < 0.5 mV or < 1.0 mV. An LVA quantification model was created with the use of clinical variables and PWR, and then validated in a separate cohort of 24 patients. Seventy-eight patients were followed for 12 months to evaluate AA recurrence. RESULTS: PWR strongly correlated with left atrial (LA) (< 0.5 mV: r = 0.60; < 1.0 mV: r = 0.68; P < 0.001) and biatrial LVA (< 0.5 mV: r = 0.63; < 1.0 mV: r = 0.70; P < 0.001). Addition of PWR to clinical variables improved model quantification of LA LVA at the < 0.5 mV (adjusted R2 = 0.59 to 0.68) and < 1.0 mV (adjusted R2 = 0.59 to 0.74) cutoffs. In the validation cohort, PWR model-predicted LVA correlated strongly with measured LVA (< 0.5 mV: r = 0.78; < 1.0 mV: r = 0.81; P < 0.001). PWR model was superior to DR-FLASH (area under the receiver operating characteristic curve [AUC] 0.90 vs 0.78; P = 0.030) and APPLE (AUC 0.90 vs 0.67; P = 0.003) at detecting LA LVA and similar at predicting AA recurrence after PVI (AUC 0.67 vs 0.65 and 0.60). CONCLUSION: Our novel PWR model accurately quantifies LVA and predicts AA recurrence after PVI. PWR model-predicted LVA may help guide patient selection for PVI.

Standard vs Augmented Ablation of Paroxysmal Atrial Fibrillation for Reduction of Atrial Fibrillation Recurrence: The AWARE Randomized Clinical Trial.

Importance: Recurrent atrial fibrillation (AF) commonly occurs after catheter ablation and is associated with patient morbidity and health care costs. Objective: To evaluate the superiority of an augmented double wide-area circumferential ablation (WACA) compared with a standard single WACA in preventing recurrent atrial arrhythmias (AA) (atrial tachycardia, atrial flutter, or atrial fibrillation [AF]) in patients with paroxysmal AF. Design, Setting, and Participants: This was a pragmatic, multicenter, prospective, randomized, open, blinded end point superiority clinical trial conducted at 10 university-affiliated centers in Canada. The trial enrolled patients 18 years and older with symptomatic paroxysmal AF from March 2015 to May 2017. Analysis took place between January and April 2022. Analyses were intention to treat. Interventions: Patients were randomized (1:1) to receive radiofrequency catheter ablation for pulmonary vein isolation with either a standard single WACA or an augmented double WACA. Main Outcomes and Measures: The primary outcome was AA recurrence between 91 and 365 days postablation. Patients underwent 42 days of ambulatory electrocardiography monitoring after ablation. Secondary outcomes included need for repeated catheter ablation and procedural and safety variables. Results: Of 398 patients, 195 were randomized to the single WACA (control) arm (mean [SD] age, 60.6 [9.3] years; 65 [33.3%] female) and 203 to the double WACA (experimental) arm (mean [SD] age, 61.5 [9.3] years; 66 [32.5%] female). Overall, 52 patients (26.7%) in the single WACA arm and 50 patients (24.6%) in the double WACA arm had recurrent AA at 1 year (relative risk, 0.92; 95% CI, 0.66-1.29; P = .64). Twenty patients (10.3%) in the single WACA arm and 15 patients (7.4%) in the double WACA arm underwent repeated catheter ablation (relative risk, 0.72; 95% CI, 0.38-1.36). Adjudicated serious adverse events occurred in 13 patients (6.7%) in the single WACA arm and 14 patients (6.9%) in the double WACA arm. Conclusions and Relevance: In this randomized clinical trial of patients with paroxysmal AF, additional ablation by performing a double ablation lesion set did not result in improved freedom from recurrent AA compared with a standard single ablation set. Trial Registration: ClinicalTrials.gov Identifier: NCT02150902.

Automated Quantification of Abnormal QRS Peaks From High-Resolution ECGs Predicts Late Ventricular Arrhythmias in Hypertrophic Cardiomyopathy: A 5-Year Prospective Multicenter Study.

Background Patients with hypertrophic cardiomyopathy (HCM) are at risk of ventricular arrhythmia (VA) attributed to abnormal electrical activation arising from myocardial fibrosis and myocyte disarray. We sought to quantify intra-QRS peaks (QRSp) in high-resolution ECGs as a measure of abnormal activation to predict late VA in patients with HCM. Methods and Results Prospectively enrolled patients with HCM (n=143, age 53±14 years) with prophylactic implantable cardioverter-defibrillators had 3-minute, high-resolution (1024 Hz), digital 12-lead ECGs recorded during intrinsic rhythm. For each precordial lead, QRSp was defined as the total number of peaks detected in the QRS complex that deviated from a smoothing filtered version of the QRS. The VA end point was appropriate implantable cardioverter-defibrillator therapy during 5-year prospective follow-up. After 5 years, 21 (16%) patients had VA. Patients who were VA positive had greater QRSp (6.0 [4.0-7.0] versus 4.0 [2.0-5.0]; P<0.01) and lower left ventricular ejection fraction (57±11 versus 62±9; P=0.038) compared with patients who were VA negative, but had similar established HCM risk metrics. Receiver operating characteristic analysis revealed that QRSp discriminated VA (area under the curve=0.76; P<0.001), with a QRSp ≥4 achieving 91% sensitivity and 39% specificity. The annual VA rate was greater in patients with QRSp ≥4 versus QRSp <4 (4.4% versus 0.98%; P=0.012). In multivariable Cox regression, age <50 years (hazard ratio [HR], 2.53; P=0.009) and QRSp (HR per QRS peak, 1.41; P=0.009) predicted VA after adjusting for established HCM risk metrics. In patients aged <50 years, the annual VA rate was 0.0% for QRSp <4 compared with 6.9% for QRSp ≥4 (P=0.012). Conclusions QRSp predicted VA in patients with HCM who were eligible for an implantable cardioverter-defibrillator after adjusting for established HCM risk metrics, such that each additional QRS peak increases VA risk by 40%. QRSp <4 was associated with a <1% annual VA risk in all patients, and no VA risk among those aged <50 years. This novel ECG metric may improve patient selection for prophylactic implantable cardioverter-defibrillator therapy by identifying those with low VA risk. These findings require further validation in a lower risk HCM cohort. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02560844.

Use of Wearable Technology and Deep Learning to Improve the Diagnosis of Brugada Syndrome.

BACKGROUND: The diagnosis of Brugada syndrome by 12-lead electrocardiography (ECG) is challenging because the diagnostic type 1 pattern is often transient. OBJECTIVES: This study sought to improve Brugada syndrome diagnosis by using deep learning (DL) to continuously monitor for Brugada type 1 in 24-hour ambulatory 12-lead ECGs (Holters). METHODS: A convolutional neural network was trained to classify Brugada type 1. The training cohort consisted of 10-second standard/high precordial leads from 12-lead ECGs (n = 1,190) and 12-lead Holters (n = 380) of patients with definite and suspected Brugada syndrome. The performance of the trained model was evaluated in 2 testing cohorts of 10-second standard/high precordial leads from 12-lead ECGs (n = 474) and 12-lead Holters (n = 716). RESULTS: DL achieved a receiver-operating characteristic area under the curve of 0.976 (95% CI: 0.973-0.979) in classifying Brugada type 1 from 12-lead ECGs and 0.975 (95% CI: 0.966-0.983) from 12-lead Holters. Compared with cardiologist reclassification of Brugada type 1, DL had similar performance and produced robust results in experiments evaluating scalability and explainability. When DL was applied to consecutive 10-second, clean ECGs from 24-hour 12-lead Holters, spontaneous Brugada type 1 was detected in 48% of patients with procainamide-induced Brugada syndrome and in 33% with suspected Brugada syndrome. DL detected no Brugada type 1 in healthy control patients. CONCLUSIONS: This novel DL model achieved cardiologist-level accuracy in classifying Brugada type 1. Applying DL to 24-hour 12-lead Holters significantly improved the detection of Brugada type 1 in patients with procainamide-induced and suspected Brugada syndrome. DL analysis of 12-lead Holters may provide a robust, automated screening tool before procainamide challenge to aid in the diagnosis of Brugada syndrome.

Augmented wide area circumferential catheter ablation for reduction of atrial fibrillation recurrence (AWARE) trial: Design and rationale.

BACKGROUND: Recurrence of atrial fibrillation (AF) after a pulmonary vein isolation procedure is often due to electrical reconnection of the pulmonary veins. Repeat ablation procedures may improve freedom from AF but are associated with increased risks and health care costs. A novel ablation strategy in which patients receive "augmented" ablation lesions has the potential to reduce the risk of AF recurrence. OBJECTIVE: The Augmented Wide Area Circumferential Catheter Ablation for Reduction of Atrial Fibrillation Recurrence (AWARE) Trial was designed to evaluate whether an augmented wide-area circumferential antral (WACA) ablation strategy will result in fewer atrial arrhythmia recurrences in patients with symptomatic paroxysmal AF, compared with a conventional WACA strategy. METHODS/DESIGN: The AWARE trial was a multicenter, prospective, randomized, open, blinded endpoint trial that has completed recruitment (ClinicalTrials.gov NCT02150902). Patients were randomly assigned (1:1) to either the control arm (single WACAlesion set) or the interventional arm (augmented- double WACA lesion set performed after the initial WACA). The primary outcome was atrial tachyarrhythmia (AA; atrial tachycardia [AT], atrial flutter [AFl] or AF) recurrence between days 91 and 365 post catheter ablation. Patient follow-up included 14-day continuous ambulatory ECG monitoring at 3, 6, and 12 months after catheter ablation. Three questionnaires were administered during the trial- the EuroQuol-5D (EQ-5D) quality of life scale, the Canadian Cardiovascular Society Severity of Atrial Fibrillation scale, and a patient satisfaction scale. DISCUSSION: The AWARE trial was designed to evaluate whether a novel approach to catheter ablation reduced the risk of AA recurrence in patients with symptomatic paroxysmal AF.

The Role of Artificial Intelligence and Machine Learning in Clinical Cardiac Electrophysiology.

In recent years, numerous applications for artificial intelligence (AI) in cardiology have been found, due in part to large digitized data sets and the evolution of high-performance computing. In the discipline of cardiac electrophysiology (EP), a number of clinical, imaging, and electrical waveform data are considered in the diagnosis, prognostication, and management of arrhythmias, which lend themselves well to automation through AI. But equally relevant, AI offers a unique opportunity to discover novel EP concepts and improve clinical care through its inherent, hierarchical tenets of self-learning. In this review we focus on the application of AI in clinical EP and summarize state-of-the art, large, clinical studies in the following key domains: (1) electrocardiogram-based arrhythmia and disease classification; (2) atrial fibrillation source detection; (3) substrate and risk assessment for atrial fibrillation and ventricular tachyarrhythmias; and (4) predicting outcomes after cardiac resynchronization therapy. Many are small, single-centre, proof-of-concept investigations, but they still show ground-breaking performance of deep learning, a subdomain of AI, which surpasses traditional statistical analysis. Larger studies, for instance classifying arrhythmias from electrocardiogram recordings, have further provided external validation of their high accuracy. Ultimately, the performance of AI is dependent on the quality of the input data and the rigour of algorithm development. The field is still nascent and several barriers will need to be overcome, including prospective validation in large, well labelled data sets and more seamless information technology-based data collection/integration, before AI can be adopted into broader clinical EP practice. This review concludes with a discussion of these challenges and future work.

Microvolt QRS Alternans in Hypertrophic Cardiomyopathy: A Novel Risk Marker of Late Ventricular Arrhythmias.

Background Unlike T-wave alternans (TWA), the relation between QRS alternans (QRSA) and ventricular arrhythmia (VA) risk has not been evaluated in hypertrophic cardiomyopathy (HCM). We assessed microvolt QRSA/TWA in relation to HCM risk factors and late VA outcomes in HCM. Methods and Results Prospectively enrolled patients with HCM (n=130) with prophylactic implantable cardioverter-defibrillators underwent digital 12-lead ECG recordings during ventricular pacing (100-120 beats/min). QRSA/TWA was quantified using the spectral method. Patients were categorized as QRSA+ and/or TWA+ if sustained alternans was present in ≥2 precordial leads. The VA end point was appropriate implantable cardioverter-defibrillator therapy over 5 years of follow-up. QRSA+ and TWA+ occurred together in 28% of patients and alone in 7% and 7% of patients, respectively. QRSA magnitude increased with pacing rate (1.9±0.6 versus 6.2±2.0 µV; P=0.006). Left ventricular thickness was greater in QRSA+ than in QRSA- patients (22±7 versus 20±6 mm; P=0.035). Over 5 years follow-up, 17% of patients had VA. The annual VA rate was greater in QRSA+ versus QRSA- patients (5.8% versus 2.0%; P=0.006), with the QRSA+/TWA- subgroup having the greatest rate (13.3% versus 2.6%; P<0.001). In those with <2 risk factors, QRSA- patients had a low annual VA rate compared QRSA+ patients (0.58% versus 7.1%; P=0.001). Separate Cox models revealed QRSA+ (hazard ratio [HR], 2.9 [95% CI, 1.2-7.0]; P=0.019) and QRSA+/TWA- (HR, 7.9 [95% CI, 2.9-21.7]; P<0.001) as the most significant VA predictors. TWA and HCM risk factors did not predict VA. Conclusions In HCM, microvolt QRSA is a novel, rate-dependent phenomenon that can exist without TWA and is associated with greater left ventricular thickness. QRSA increases VA risk 3-fold in all patients, whereas the absence of QRSA confers low VA risk in patients with <2 risk factors. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02560844.

Deep Learning Classification of Unipolar Electrograms in Human Atrial Fibrillation: Application in Focal Source Mapping.

Focal sources are potential targets for atrial fibrillation (AF) catheter ablation, but they can be time-consuming and challenging to identify when unipolar electrograms (EGM) are numerous and complex. Our aim was to apply deep learning (DL) to raw unipolar EGMs in order to automate putative focal sources detection. We included 78 patients from the Focal Source and Trigger (FaST) randomized controlled trial that evaluated the efficacy of adjunctive FaST ablation compared to pulmonary vein isolation alone in reducing AF recurrence. FaST sites were identified based on manual classification of sustained periodic unipolar QS EGMs over 5-s. All periodic unipolar EGMs were divided into training (n = 10,004) and testing cohorts (n = 3,180). DL was developed using residual convolutional neural network to discriminate between FaST and non-FaST. A gradient-based method was applied to interpret the DL model. DL classified FaST with a receiver operator characteristic area under curve of 0.904 ± 0.010 (cross-validation) and 0.923 ± 0.003 (testing). At a prespecified sensitivity of 90%, the specificity and accuracy were 81.9 and 82.5%, respectively, in detecting FaST. DL had similar performance (sensitivity 78%, specificity 89%) to that of FaST re-classification by cardiologists (sensitivity 78%, specificity 79%). The gradient-based interpretation demonstrated accurate tracking of unipolar QS complexes by select DL convolutional layers. In conclusion, our novel DL model trained on raw unipolar EGMs allowed automated and accurate classification of FaST sites. Performance was similar to FaST re-classification by cardiologists. Future application of DL to classify FaST may improve the efficiency of real-time focal source detection for targeted AF ablation therapy.

Unipolar electrogram-based voltage mapping with far-field cancellation to improve detection of abnormal atrial substrate during atrial fibrillation.

INTRODUCTION: An important substrate for atrial fibrillation (AF) is fibrotic atrial myopathy. Identifying low voltage, myopathic regions during AF using traditional bipolar voltage mapping is limited by the directional dependency of wave propagation. Our objective was to evaluate directionally independent unipolar voltage mapping, but with far-field cancellation, to identify low-voltage regions during AF. METHODS: In 12 patients undergoing pulmonary vein isolation for AF, high-resolution voltage mapping was performed in the left atrium during sinus rhythm and AF using a roving 20-pole circular catheter. Bipolar electrograms (EGMs) (Bi) < 0.5 mV in sinus rhythm identified low-voltage regions. During AF, bipolar voltage and unipolar voltage maps were created, the latter with (uni-res) and without (uni-orig) far-field cancellation using a novel, validated least-squares algorithm. RESULTS: Uni-res voltage was ~25% lower than uni-orig for both low voltage and normal atrial regions. Far-field EGM had a dominant frequency (DF) of 4.5-6.0 Hz, and its removal resulted in a lower DF for uni-orig compared with uni-res (5.1 ± 1.5 vs. 4.8 ± 1.5 Hz; p < .001). Compared with Bi, uni-res had a significantly greater area under the receiver operator curve (0.80 vs. 0.77; p < .05), specificity (86% vs. 76%; p < .001), and positive predictive value (43% vs. 30%; p < .001) for detecting low-voltage during AF. Similar improvements in specificity and positive predictive value were evident for uni-res versus uni-orig. CONCLUSION: Far-field EGM can be reliably removed from uni-orig using our novel, least-squares algorithm. Compared with Bi and uni-orig, uni-res is more accurate in detecting low-voltage regions during AF. This approach may improve substrate mapping and ablation during AF, and merits further study.

Focal and pseudo/rotational activations in human atrial fibrillation defined with automated periodicity mapping.

INTRODUCTION: Defining atrial fibrillation (AF) wave propagation is challenging unless local signal features are discrete or periodic. Periodic focal or rotational activity may identify AF drivers. Our objective was to characterize AF propagation at sites with periodic activation to evaluate the prevalence and relationship between focal and rotational activation. METHODS: We included 80 patients (61 ± 10 years, persistent AF 49%) from the FaST randomized trial that compared the efficacy of adjunctive focal site ablation versus pulmonary vein isolation. Patients underwent left atrial (LA) activation mapping with a 20-pole circular catheter during spontaneous or induced AF. Five-second bipolar and unipolar electrograms in AF were analyzed. Periodic sites were identified by spectral analysis of the bipolar electrogram. Activation maps of periodic sites were constructed using an automated, validated tracking algorithm, and classified into three patterns: focal sites (FS), rotation (RO), or pseudo-rotation (pRO). RESULTS: The most common propagation pattern at periodic sites was FS for 5-s in all patients (4.9 ± 1.9 per patient). RO and pRO were observed in two and seven patients, respectively, but were all transient (3-5 cycles). Activation from a FS evolved into transient RO/pRO in five patients. No patient had autonomous RO/pRO activations. Patients with RO/pRO had greater LA surface area with periodicity (78 ± 7 vs. 63 ± 16%, p = .0002) and shorter LA periodicity CL (166 ± 10 vs. 190±28 ms, p = .0001) than the rest. CONCLUSION: Using automated, regional AF periodicity mapping, FS is more prevalent and temporally stable than RO/pRO. Most RO/pRO evolve from neighboring FS. These findings and their implications for AF maintenance require verification with global, panoramic mapping.

Microvolt QRS Alternans Without Microvolt T-Wave Alternans in Human Cardiomyopathy: A Novel Risk Marker of Late Ventricular Arrhythmias.

Background Action potential alternans can induce ventricular tachyarrhythmias and manifest on the surface ECG as T-wave alternans (TWA) and QRS alternans (QRSA). We sought to evaluate microvolt QRSA in cardiomyopathy patients in relation to TWA and ventricular tachyarrhythmia outcomes. Methods and Results Prospectively enrolled cardiomyopathy patients (n=100) with prophylactic defibrillators had 12-lead ECGs recorded during ventricular pacing from 100 to 120 beats/min. QRSA and TWA were quantified in moving 128-beat segments using the spectral method. Segments were categorized as QRSA positive (QRSA+) and/or TWA positive (TWA+) based on ≥2 precordial leads having alternans magnitude >0 and signal:noise >3. Patients were similarly categorized based on having ≥3 consecutive segments with alternans. TWA+ and QRSA+ occurred together in 31% of patients and alone in 18% and 14% of patients, respectively. Although TWA magnitude (1.4±0.4 versus 4.7±1.0 µV, P<0.01) and proportion of TWA+ studies (16% versus 46%, P<0.01) increased with rate, QRSA did not change. QRS duration was longer in QRSA+ than QRSA-negative patients (138±23 versus 113±26 ms, P<0.01). At 3.5 years follow-up, appropriate defibrillator therapy or sustained ventricular tachyarrhythmia was greater in QRSA+ than QRSA-negative patients (30% versus 8%, P=0.02) but similar in TWA+ and TWA-negative patients. Among QRSA+ patients, the event rate was greater in those without TWA (62% versus 21%, P=0.02). Multivariable Cox analysis revealed QRSA+ (hazard ratio [HR], 4.6; 95% CI, 1.5-14; P=0.009) and QRS duration >120 ms (HR, 4.1; 95% CI, 1.3-12; P=0.014) to predict events. Conclusions Microvolt QRSA is novel phenomenon in cardiomyopathy patients that can exist without TWA and is associated with QRS prolongation. QRSA increases the risk of ventricular tachyarrhythmia 4-fold, which merits further study as a risk stratifier.

Focal source and trigger mapping in atrial fibrillation: Randomized controlled trial evaluating a novel adjunctive ablation strategy.

BACKGROUND: Intraoperative mapping has demonstrated focal activations during human atrial fibrillation (AF). These putative AF sources can manifest sustained periodic bipolar and unipolar QS electrograms (EGMs). We have automated the detection of these EGM features using our validated Focal Source and Trigger (FaST) computational algorithm. OBJECTIVE: The purpose of this study was to conduct a randomized controlled pilot evaluating the feasibility and efficacy of FaST mapping/ablation as an adjunct to pulmonary vein isolation (PVI) in reducing AF recurrence. METHODS: We randomized 80 patients with high-burden paroxysmal or persistent AF (age 61 ± 10 years; 75% male) to PVI alone (n = 41) or PVI+FaST mapping/ablation (n = 39). The primary endpoint was time to AF recurrence >30 seconds between 3 and 12 months after 1 procedure. RESULTS: FaST sites were identified in all but 1 patient and were localized to pulmonary vein (PV) (2.1 ± 1.1 per patient) and extra-PV regions (2.8 ± 1.4 per patient). FaST mapping and ablation times were 27 ± 9 minutes and 8.5 ± 5 minutes, respectively. Patients with AF termination during ablation had greater AF cycle length prolongation with PVI+FaST than PVI (Δ20 ± 14 ms vs Δ5 ± 17 ms; P = .046). Freedom from AF recurrence at 12 months was higher in PVI+FaST vs PVI for patients off antiarrhythmic drugs (74% vs 51%; hazard ratio 0.48; 95% confidence interval 0.21-1.08; P = .064) but did not quite reach statistical significance. Major adverse events were similar between the 2 groups. CONCLUSION: In this randomized controlled pilot, real-time FaST mapping provided an intuitive, automated approach for localizing focal AF sources. FaST ablation as an adjunct to PVI may reduce AF recurrence, which requires verification with a larger multicenter trial.

Arrhythmias and Sudden Cardiac Death in End Stage Renal Disease: Epidemiology, Risk Factors, and Management.

Patients with end-stage renal disease (ESRD) are predisposed to heart rhythm disorders resulting in significant morbidity and mortality. Bradyarrhythmia appears to be more prevalent than ventricular tachyarrhythmias. There is also a high incidence of sudden cardiac death (SCD) in this group of patients, which cannot be explained only by traditional cardiac risk factors. The reported incidence and prevalence of arrhythmias and SCD is quite variable mainly because of the different study populations and recording techniques. The mechanism of SCD in patients with ESRD is also not clear. Although traditionally the thinking has been that ventricular arrhythmias are the main contributor to SCD, recent studies with implantable loop recorders have highlighted the role of bradyarrhythmias. The pathophysiological processes resulting in arrhythmia and SCD in patients with ESRD are unique. Some of the risk factors, including dialysate composition, timing, and frequency, are modifiable and hence provide an option for interventions to potentially reduce SCD. In addition, there might be a relationship with the timing of dialysis with SCD tending to occur during the long interdialytic period. Patients with ESRD have a higher likelihood of requiring pacemaker implantation; however, they also have a higher risk of device-related complications. The limited data available regarding the role of the implantable cardioverter defibrillator to prevent SCD in patients with ESRD have shown conflicting results. Future research is needed to develop appropriate risk stratification tools to identify patients who will benefit from such interventions and to assess their safety and efficacy.

Quantification of abnormal QRS peaks predicts response to cardiac resynchronization therapy and tracks structural remodeling.

BACKGROUND: Although QRS duration (QRSd) is an important determinant of cardiac resynchronization therapy (CRT) response, non-responder rates remain high. QRS fragmentation can also reflect electrical dyssynchrony. We hypothesized that quantification of abnormal QRS peaks (QRSp) would predict CRT response. METHODS: Forty-seven CRT patients (left ventricular ejection fraction = 23±7%) were prospectively studied. Digital 12-lead ECGs were recorded during native rhythm at baseline and 6 months post-CRT. For each precordial lead, QRSp was defined as the total number of peaks detected on the unfiltered QRS minus those detected on a smoothed moving average template QRS. CRT response was defined as >5% increase in left ventricular ejection fraction post-CRT. RESULTS: Sixty-percent of patients responded to CRT. Baseline QRSd was similar in CRT responders and non-responders, and did not change post-CRT regardless of response. Baseline QRSp was greater in responders than non-responders (9.1±3.5 vs. 5.9±2.2, p = 0.001) and decreased in responders (9.2±3.6 vs. 7.9±2.8, p = 0.03) but increased in non-responders (5.5±2.3 vs. 7.5±2.8, p = 0.049) post-CRT. In multivariable analysis, QRSp was the only independent predictor of CRT response (Odds Ratio [95% Confidence Interval]: 1.5 [1.1-2.1], p = 0.01). ROC analysis revealed QRSp (area under curve = 0.80) to better discriminate response than QRSd (area under curve = 0.67). Compared to QRSd ≥150ms, QRSp ≥7 identified response with similar sensitivity but greater specificity (74 vs. 32%, p<0.05). Amongst patients with QRSd <150ms, more patients with QRSp ≥7 responded than those with QRSp <7 (75 vs. 0%, p<0.05). CONCLUSIONS: Our novel automated QRSp metric independently predicts CRT response and decreases in responders. Electrical dyssynchrony assessed by QRSp may improve CRT selection and track structural remodeling, especially in those with QRSd <150ms.