Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation.

BACKGROUND: In patients with symptomatic paroxysmal atrial fibrillation that has not responded to medication, catheter ablation is more effective than antiarrhythmic drug therapy for maintaining sinus rhythm. However, the safety and efficacy of cryoballoon ablation as initial first-line therapy have not been established. METHODS: We performed a multicenter trial in which patients 18 to 80 years of age who had paroxysmal atrial fibrillation for which they had not previously received rhythm-control therapy were randomly assigned (1:1) to receive treatment with antiarrhythmic drugs (class I or III agents) or pulmonary vein isolation with a cryoballoon. Arrhythmia monitoring included 12-lead electrocardiography conducted at baseline and at 1, 3, 6, and 12 months; patient-activated telephone monitoring conducted weekly and when symptoms were present during months 3 through 12; and 24-hour ambulatory monitoring conducted at 6 and 12 months. The primary efficacy end point was treatment success (defined as freedom from initial failure of the procedure or atrial arrhythmia recurrence after a 90-day blanking period to allow recovery from the procedure or drug dose adjustment, evaluated in a Kaplan-Meier analysis). The primary safety end point was assessed in the ablation group only and was a composite of several procedure-related and cryoballoon system-related serious adverse events. RESULTS: Of the 203 participants who underwent randomization and received treatment, 104 underwent ablation, and 99 initially received drug therapy. In the ablation group, initial success of the procedure was achieved in 97% of patients. The Kaplan-Meier estimate of the percentage of patients with treatment success at 12 months was 74.6% (95% confidence interval [CI], 65.0 to 82.0) in the ablation group and 45.0% (95% CI, 34.6 to 54.7) in the drug-therapy group (P<0.001 by log-rank test). Two primary safety end-point events occurred in the ablation group (Kaplan-Meier estimate of the percentage of patients with an event within 12 months, 1.9%; 95% CI, 0.5 to 7.5). CONCLUSIONS: Cryoballoon ablation as initial therapy was superior to drug therapy for the prevention of atrial arrhythmia recurrence in patients with paroxysmal atrial fibrillation. Serious procedure-related adverse events were uncommon. (Supported by Medtronic; STOP AF First ClinicalTrials.gov number, NCT03118518.).

LBBB and heart failure-Relationships among QRS amplitude, duration, height, LV mass, and sex.

BACKGROUND: Height, left ventricular (LV) size, and sex were proposed as additional criteria for patient selection for cardiac resynchronization therapy (CRT) but their connections with the QRS complex in left bundle branch block (LBBB) are little investigated. We evaluated these. METHODS: Among patients with "true" LBBB, QRS duration (QRSd) and amplitude, and LV hypertrophy indices, were correlated with patient's height and LV mass, and compared between sexes. RESULTS: In this study cohort (n = 220; 60 ± 12 years; left ventricular ejection fraction [LVEF] 21 ± 7%; mostly New York Heart Association II-III, QRSd 165 ± 19 ms; 57% female; 70% responders [LVEF increased ≥5%]), LV mass was increased in all patients. QRS amplitude did not correlate with LV mass or height in any individual lead or with Sokolow-Lyon or Cornell-Lyon indices. QRSd did not correlate with height. In contrast, QRSd correlated strongly with LV mass (r = .51). CRT response rate was greater in women versus men (84% vs. 58%, p < .001) despite shorter QRSd [7% shorter (p < .0001)]. QRSd normalized for height resulted in a 2.7% and for LV mass 24% greater index in women. CONCLUSION: True LBBB criteria do not exclude HF patients with increased LV mass. QRS amplitudes do not correlate with height or LV mass. Height does not affect QRSd. However, QRSd correlates with LV size. QRSd normalized for LV mass results in 24% greater value in women in the direction of sex-specific responses. LV mass may be a significant nonelectrical modifier of QRSd for CRT.

Influence of "high" defibrillation thresholds on patient survival and impact of system modification.

OBJECTIVE: To test whether a high defibrillation threshold (DFT) marks patients with poor outcomes which are improved when DFT is decreased by system modification (subcutaneous coil implant; SM). BACKGROUND: The electrical substrate generating fast ventricular arrhythmias may generate poor outcomes among patients treated with implantable cardioverter-defibrillators (ICDs), even when arrhythmias are treated successfully. Since patients with high DFTs have increased mortality, we contrasted survival among patients with high DFT treated with and without SM. METHODS: We studied consecutive patients undergoing ICD implantation and DFT testing at Cleveland Clinic over a 14-year period. High DFT was defined as successful defibrillation by shock strength >25 J or ≤10 J of maximal device output. Mortality was recorded using the Social Security Death Index. Survival was compared among those high DFT patients receiving SM versus the remainder. RESULTS: Out of 6353 patients tested, 191 (3%) had high DFT (32.1 ± 3.7 J) versus 13.9 ± 4.9 J in the remainder ("acceptable DFT," p < .001). One hundred twenty-one high DFT patients (63%; 33.3 ± 3.4 J) underwent SM, which significantly decreased DFT (24.8 ± 5.9 J; p < .001). Seventy patients (37%; 30.3 ± 3.3 J) did not undergo SM. During follow-up, 38% (2363/6162; 7.8 yrs) patients with acceptable DFT died versus 48% high DFT patients (91/191; 5.6 yrs.; p < .001). Concomitantly, 48% patients with SM (58/121) died, as compared to 47% patients (33/70) without SM (p = .91); median follow-up 4.9 yrs). CONCLUSION: Patients with high DFT have a higher mortality than those with acceptable DFT. The additional subcutaneous coil implant decreases DFT to an acceptable range but does not appear to improve survival. The electrical substrate underlying high DFT appears to determine survival.

Acute safety, efficacy, and advantages of a novel cryoballoon ablation system for pulmonary vein isolation in patients with paroxysmal atrial fibrillation: initial clinical experience.

AIMS: Cryoballoon pulmonary vein isolation (PVI) is a safe and effective treatment for atrial fibrillation (AF). Current limitations include incomplete vein occlusion due to balloon rigidity and inconsistent electrogram recording, which impairs identification of isolation. We aimed to evaluate the acute safety and performance of a novel cryoballoon system. METHODS AND RESULTS: The system includes a steerable sheath, mapping catheter, and a balloon that maintains uniform inflation pressure and size following initiation of ablation. Protocol-directed cryoablation was delivered for 180 s for isolation documented in ≤60 s, otherwise freeze duration was 240 s. Primary endpoints were acute safety and vein isolation. Pulmonary vein isolation was confirmed at ≥30 min post-isolation. Data were compared across vein locations. Thirty patients with paroxysmal AF were enrolled at two centres and underwent PVI. Pulmonary vein isolation was achieved with cryoablation only in 100% of veins (120/120). Nadir temperature was -53.1 ± 5.3°C. The number of applications to achieve PVI was 1.4 ± 0.4 per vein. Of the 120 veins, 89 were isolated with a single cryothermal application (10/30 patients required only 4 total cryoablations). There were no procedural- or device-related serious adverse events at 30 days post-procedure. A subset (24/30) of patients was followed for 1-year and 71% (17/24) remained free of atrial arrhythmias. Six patients with arrhythmia recurrence were remapped and three had durable PVI for all four veins. CONCLUSION: In this first human experience, the novel cryoballoon platform was safe, efficacious, and demonstrated a high proportion of successful single ablation isolation.

Attenuated heart rate recovery is associated with higher arrhythmia recurrence and mortality following atrial fibrillation ablation.

AIMS: Heart rate recovery (HRR), the decrease in heart rate occurring immediately after exercise, is caused by the increase in vagal activity and sympathetic withdrawal occurring after exercise and is a powerful predictor of cardiovascular events and mortality. The extent to which it impacts outcomes of atrial fibrillation (AF) ablation has not previously been studied. The aim of this study is to investigate the association between attenuated HRR and outcomes following AF ablation. METHODS AND RESULTS: We studied 475 patients who underwent EST within 12 months of AF ablation. Patients were categorized into normal (>12 b.p.m.) and attenuated (≤12 b.p.m.) HRR groups. Our main outcomes of interest included arrhythmia recurrence and all-cause mortality. During a mean follow-up of 33 months, 43% of our study population experienced arrhythmia recurrence, 74% of those with an attenuated HRR, and 30% of those with a normal HRR (P < 0.0001). Death occurred in 9% of patients in the attenuated HRR group compared to 4% in the normal HRR cohort (P = 0.001). On multivariable models adjusting for cardiorespiratory fitness (CRF), medication use, left atrial size, ejection fraction, and renal function, attenuated HRR was predictive of increased arrhythmia recurrence (hazard ratio 2.54, 95% confidence interval 1.86-3.47, P < 0.0001). CONCLUSION: Heart rate recovery provides additional valuable prognostic information beyond CRF. An impaired HRR is associated with significantly higher rates of arrhythmia recurrence and death following AF ablation.

Predictors of long-term outcomes greater than 10 years after cardiac resynchronization therapy implantation.

BACKGROUND: Cardiac resynchronization therapy (CRT) is indicated in patients with medically refractory heart failure and wide QRS duration. While much is known about predictors of left ventricular (LV) remodeling after CRT implantation and short-term mortality, limited data exist on long-term outcomes after CRT placement. METHODS: We retrospectively reviewed all patients undergoing CRT implantation at our center between 2003 and 2008 and examined mortality using institutional electronic records, social security death index, and online obituary search. We included only patients with preimplant echoes with LV ejection fraction (LVEF) 35% or below. Variable selection was performed using stepwise regression and models were compared using goodness-of-fit criteria. A final model was validated with the bootstrap regression method. RESULTS: Out of the 877 CRT patients undergoing implantation during this time, 287 (32.7%) survived longer than 10 years. Significant (P < .05) predictors of survival in our multivariate model were age, left ventricular diastolic diameter, sex, presence of nonischemic vs ischemic cardiomyopathy, QRS duration, atrial fibrillation, BNP levels, and creatinine levels at the time of CRT implantation. A model using the odds ratios from these variables had a receiver operating curve with an area under the curve score of 0.816 (standard error, 0.019) at predicting survival or freedom from LVAD or heart transplant for longer than 10 years after CRT implantation. The specificity for factors 3 or above and 5 or above was 68% and 77%, respectively. CONCLUSION: A large proportion of patients are still alive 10 years after CRT implantation. Variables at the time of CRT implant can help provide prognostic information to patients and electrophysiologists to determine the long-term benefit and survival of patients after CRT implantation.

Baseline Right Ventricular Dysfunction Predicts Worse Outcomes in Patients Undergoing Cardiac Resynchronization Therapy Implantation.

INTRODUCTION: Cardiac resynchronization therapy (CRT) has been shown to improve survival in patients with systolic heart failure, wide QRS duration, and left-bundle-branch-block. However, CRT outcomes stratified by right ventricular (RV) function at implant have not been well studied. METHODS: We retrospectively reviewed patients at Cleveland Clinic who underwent CRT implantation (n = 777) from 2003 to 2011 with a diagnosis of heart failure, echocardiography with both pre-CRT left ventricular ejection fraction (LVEF) ≤35% and available post-CRT echocardiography at 6 months post-implant. CRT response was defined as LVEF improvement ≥5%. Patients were separated into 2 groups: normal or mild RV dysfunction (n = 570) labeled Normal RV; moderate to severe dysfunction (n = 207) labeled RV DYSFXN based on qualitative echocardiography assessment. Survival was calculated as time from CRT implant to death, left ventricular assist device implant, or heart transplant. RESULTS: CRT response was significantly higher in patients with Normal RV (67%) compared with patients with RV DYSFXN (56%; P = .006). Kaplan-Meier analysis showed that CRT patients with Normal RV had significantly greater survival compared with patients with RV DYSFXN (P < .001). In multivariable Cox regression accounting for a priori covariates, RV DYSFXN was associated with worse survival (HR 1.41 [95% CI: 1.14-1.75], P = .002) and lower CRT response (HR 0.66 [95% CI: 0.44-0.97], P = .03). CONCLUSION: Baseline RV dysfunction at CRT implant is an important predictor of worsened left ventricular remodeling and survival in CRT patients.

Long term outcomes in patients with chronic right ventricular pacing upgraded to cardiac resynchronization therapy.

INTRODUCTION: In patients with chronic systolic heart failure and frequent right ventricular pacing (RVP), upgrade to cardiac resynchronization therapy (CRT) has become common practice despite a lack of randomized clinical trials. We aimed to evaluate long term outcomes in patients upgraded to CRT from chronic RVP compared with de novo CRT implants. METHODS AND RESULTS: We reviewed medical charts on consecutive patients with a left ventricular ejection fraction (LVEF) ≤ 35% and a QRSd ≥ 120 ms undergoing CRT. Survival free of left ventricular assist device (LVAD) and a heart transplant was compared amongst patients on the basis of pre-CRT QRS morphology. Improvement in LVEF was also compared across groups. A total of 1260 patients met inclusion criteria of whom 233 were upgraded from chronic RVP. Over a mean follow up 6.5 ± 4.0 years there were 821 endpoints (27 LVAD, 30 heart transplants, and 764 deaths). In a multivariate Cox regression model, upgraded patients had worse outcomes (HR 1.3(1.1-1.7) P = .007) compared with those with native LBBB and similar outcomes to patients with non-LBBB(HR 0.96(0.76-1.21) P = .7). The survival curve for chronic RVP parallels native LBBB for approximately 2.5 years before dropping sharply. Patients with chronic RVP derive similar improvements in LVEF compared with those with LBBB and superior improvements compared with those with non-LBBB. CONCLUSIONS: Despite achieving similar levels of LVEF improvement, patients with systolic heart failure with chronic RVP undergoing upgrade to CRT have inferior long term outcomes compared with patients with native LBBB. Long term outcomes with CRT in patients with chronic RVP, RBBB, and IVCD are similar.

Echocardiographic Predictors of Long-Term Survival in Patients Undergoing Cardiac Resynchronization Therapy: What Is the Optimal Metric?

BACKGROUND: Multiple definitions of reverse ventricular remodeling (RVR) employing various changes in left ventricular end-systolic (LVESV) or diastolic volumes (LVEDVs) or left ventricular ejection fraction (LVEF) have been used in determining cardiac resynchronization therapy (CRT) response, making comparability across studies difficult. We compared different metrics to each other, and in combination, in terms of association with long-term outcomes. METHODS: We collected clinical and echocardiographic data on 436 patients undergoing CRT. LVEF was assessed via a combined volumetric and visual assessment. Volumes were manually traced. Using a nested multivariate model of a priori determined predictors of long-term survival free of left ventricular assist device (LVAD) or heart transplant, multiple definitions of RVR were added to the model individually to determine which provided the best model fit. RESULTS: Over a mean follow-up of 5.4 ± 2.3 years, there were 198 endpoints (10 LVADs, 15 heart transplants, and 173 deaths). When added to a nested model controlling for multiple potential confounders, all definitions of RVR were significantly associated with improved survival. Changes in LVEF and LVESV were superior to changes in LVEDV. A combination metric of an LVEF improvement ≥ 5% and LVESV reduction ≥ 10% was the best overall metric for model fit. CONCLUSIONS: Changes in LVESV and LVEF are better predictors of long-term outcome following CRT compared to changes in LVEDV. Adding an assessment of LVEF to reduction in LVESV ≥ 10% provided the best overall definition for RVR in predicting CRT outcomes.

Left Ventricular Size does not Modify the Effect of QRS Duration in Predicting Response to Cardiac Resynchronization Therapy.

BACKGROUND: QRS duration (QRSd) may be impacted by both left ventricular (LV) dilatation and conduction delay. It is possible therefore that the same QRSd may portend significantly different amounts of LV activation delay in patients with small versus large left ventricles. We hypothesized that LV size modifies the effect of QRSd on predicting outcomes in patients undergoing CRT implant. METHODS: We extracted data on consecutive patients presenting for initial CRT implant. In patients with a follow-up echocardiogram, response was defined as an absolute improvement in LV ejection fraction ≥5%. Multivariate models were created to determine if left ventricular end-diastolic diameter (LVEDD) modified the effect of QRSd on its association with both long-term survival free of left ventricular assist device (LVAD) and heart transplant and echocardiographic response. RESULTS: 464 patients met inclusion criteria. At a mean follow-up of 4.9 ± 2.6 years, there were 210 deaths, 13 heart transplants, and 12 LVAD placements. There was a weak but significant correlation between baseline QRSd and LVEDD (Spearman's Rho 0.106, P < 0.001). In a multivariate analysis, there was no evidence of effect modification of LVEDD on QRSd (LVEDDi*QRS interaction term HR 1.0 [0.995-1.006], P = 0.94). Note that 305 patients had a follow-up echocardiogram, of whom 193 met the criteria for response. In a multivariate analysis, there was no evidence of effect modification of LVEDD on QRSd (LVEDDi*QRS interaction term odds ratio 0.998 (0.988-1.008), P = 0.65). CONCLUSION: LV size does not modify the effect of QRSd and its association with outcomes following CRT. The correlation between LV size and QRSd in patients with a QRSd ≥ 120 ms is weak.

Early Changes in QRS Frequency Following Cardiac Resynchronization Predict Hemodynamic Response in Left Bundle Branch Block Patients.

INTRODUCTION: QRS characteristics are the cornerstone of patient selection in cardiac resynchronization therapy (CRT) and the presence of left bundle branch block (LBBB) and baseline QRS ≥150 milliseconds portends a good outcome. We previously showed that baseline QRS frequency analysis adds predictive value to LBBB alone and have hypothesized that a change in frequency characteristics following CRT may produce additional predictive value. METHODS: We examined the QRS frequency characteristics of 182 LBBB patients before and soon after CRT. Patients were assigned to responder and nonresponder groups. Responders were defined by a decrease in left ventricular end-systolic volume (LVESV) ≥15% following CRT. We analyzed the QRS in ECG leads I, AVF, and V3 before and soon after CRT using the discrete Fourier transform algorithm. The percentage of total QRS power within discrete frequency intervals before and after CRT was calculated. The reduction in lead V3 power <10 Hz was the best indicator of response. RESULTS: Baseline QRS width was similar between the responders and nonresponders (162.2 ± 17.2 milliseconds vs. 158 ± 22.1 milliseconds, respectively; P = 0.180). Responders exhibited a greater reduction in QRS power <10 Hz (-17.0 ± 11.9% vs. -6.6 ± 12.5%; P < 0.001) and a significant AUC (0.743; P < 0.001). A ≥8% decline in QRS power <10 Hz produced the best predictive values (PPV = 84%, NPV = 59%). Importantly, when patients with baseline QRS <150 milliseconds were compared, the AUC improved (0.892, P < 0.001). CONCLUSIONS: Successful CRT produces a significant reduction in QRS power below 10 Hz, particularly when baseline QRS <150 milliseconds. These results indicate that QRS frequency changes after CRT provide additional predictive value to QRS alone.

Left ventricular hypertrophy and antiarrhythmic drugs in atrial fibrillation: impact on mortality.

BACKGROUND: Despite sparse clinical data, current atrial fibrillation (AF) guidelines favor amiodarone as a drug of choice for patients with left ventricular hypertrophy (LVH). OBJECTIVE: This study tested the hypothesis that patients with persistent AF and LVH on nonamiodarone antiarrhythmics have higher mortality compared to patients on amiodarone. METHODS: In an observational cohort analysis of patients who underwent cardioversion for AF, patients with LVH, defined as left ventricular wall thickness ≥1.4 cm, by echocardiogram prior to their first cardioversion, were included; clinical data, including antiarrhythmic drugs and ejection fraction (LVEF), were collected. Mortality, determined via the Social Security Death Index, was analyzed using Kaplan-Meier and Cox proportional hazards models to determine whether antiarrhythmic drugs were associated with higher mortality. RESULTS: In 3,926 patients, echocardiographic wall thickness was available in 1,399 (age 66.8 ± 11.8 years, 67% male, LVEF 46 ± 15%, septum 1.3 ± 0.4, posterior wall 1.2 ± 0.2 cm), and 537 (38%) had LVH ≥1.4 cm. Among 537 patients with LVH, mean age was 67.5 ± 11.7 years, 76.4% were males, and mean LVEF was 48.3 ± 13.3%. Amiodarone was associated with lower survival (log rank P = 0.001), including after adjusting for age, LVEF, and coronary artery disease (P = 0.023). In propensity-score matched cohorts with LVH treated with no drugs, nonamiodarone antiarrhythmic drugs (non-AADs), or amiodarone (N = 65 each group), there was early lower survival in patients on amiodarone (P = 0.05). CONCLUSIONS: Patients with persistent AF and LVH on non-AADs do not have higher mortality compared to patients on amiodarone. Importantly, these findings do not support amiodarone as a superior choice in patients with LVH.

Real-time guidewire localization using impedance-based electroanatomic mapping: experimental results and clinical validation during cryoballoon ablation of atrial fibrillation.

AIMS: Cryoballoon ablation is an emerging therapy for atrial fibrillation (AF). However, the Arctic Front cryoballoon (Medtronic) cannot be localized on current electroanatomic mapping (EAM) systems. We describe a technique to visualize guidewires in an impedance-based EAM system. METHODS AND RESULTS: A novel technique for real-time guidewire localization in an EAM (Ensite Velocity, St Jude Medical) was prospectively evaluated among patients referred for cryoballoon AF ablation. The guidewire was visualized as an 'orb' on the EAM and localization in each of the pulmonary veins (PVs) compared with orthogonal fluoroscopy, contrast venography, and intra-cardiac echocardiography. Application of the technique in 21 consecutive patients [median age 58 (interquartile range 21); 71.4% male; 85.7% paroxysmal AF] demonstrated agreement with respect to guidewire localization in 82 of 82 (100%) PVs. Discrimination of guidewire position in the left atrial appendage from the left PVs was also demonstrated. When compared with 21 consecutive cryoballoon procedures over the same time period in which the technique was not used, fluoroscopy time was reduced [median 53.2 (25.9) vs. 72.3 (47.6) min, P = 0.008], and a trend towards reduced radiation exposure [median 372 (656.0) vs. 581 (849.9) mGy, P = 0.08] was noted, without effect on acute procedural or mid-term endpoints. Ex vivo assessment of the technique in a saline bath left atrial model demonstrated that the 'orb' localizes to the centroid of the exposed portion of the guidewire. CONCLUSION: This simple, novel technique provides real-time, accurate guidewire localization to enable guidewire and catheter navigation during cryoballoon AF ablation.

High predictive value of paced QRS frequency in verification of left bundle branch pacing.

BACKGROUND: Left bundle branch area pacing (LBBAP) is a newer technique to deliver more synchronous left ventricular activation. Several criteria have been proposed, but not fully validated, to confirm LBBAP during implantation of the pacing lead. Spectral analysis has been used to characterize the frequency components of the clinical QRS utilizing the Fourier transform algorithm. We hypothesized that higher frequency content of the paced QRS complex may show predictive value of successful LBBAP. METHODS: We evaluated 84 patients with ejection fraction > 50%, who underwent LBB lead placement (n = 42) using ≥ 1 current criteria and right ventricular midseptal (RVsp) lead placement (n = 42) from 2000 to 2022. Time frequency analysis (Matlab) was used to determine the frequency content of the paced QRS complex. The centroid frequency (CF), which is the weighted average QRS frequency, was calculated. RESULTS: Patients in RVsp group had a longer paced QRS duration (155.6 ± 28.0 vs 127.1 ± 17.2, p < 0.002) compared to the LBBAP group. Of all standard ECG leads, the paced QRS in V2 gave the greatest difference of the CF of the LBBAP group at 8.8 ± 1.6 Hz versus 5.7 ± 0.7 Hz of the RVsp group. This difference was significant by both univariate (p < 0.003) and multivariate (p < 0.010) analysis. Predictive value of the CF for successful LBB pacing in lead V2 was highest with an AUC of 0.98. The sensitivity and specificity were 88.1% and 97.6%, respectively. CONCLUSION: Spectral analysis predicts successful LBBAP with higher frequency content when compared to RVsp pacing. Given the limitations to the current criteria to confirm LBBAP, intraprocedural use of frequency content analysis of the paced QRS complex in patients may prove useful at verifying LBB capture if verified by prospective clinical trials.

Postapproval Study of a Subcutaneous Implantable Cardioverter-Defibrillator System.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) was developed to avoid complications related to transvenous implantable cardioverter-defibrillator (TV-ICD) leads. Device safety and efficacy were demonstrated previously with atypical clinical patients or limited follow-up. OBJECTIVES: The S-ICD PAS (Subcutaneous Implantable Cardioverter-Defibrillator System Post Approval Study) is a real-world, multicenter, registry of U.S. centers that was designed to assess long-term S-ICD safety and efficacy in a diverse group of patients and implantation centers. METHODS: Patients were enrolled in 86 U.S. centers with standard S-ICD indications and were observed for up to 5 years. Efficacy endpoints were first and final shock efficacy. Safety endpoints were complications directly related to the S-ICD system or implantation procedure. Endpoints were assessed using prespecified performance goals. RESULTS: A total of 1,643 patients were prospectively enrolled, with a median follow-up of 4.2 years. All prespecified safety and efficacy endpoint goals were met. Shock efficacy rates for discrete episodes of ventricular tachycardia or ventricular fibrillation were 98.4%, and they did not differ significantly across follow-up years (P = 0.68). S-ICD-related and electrode-related complication-free rates were 93.4% and 99.3%, respectively. Only 1.6% of patients had their devices replaced by a TV-ICD for a pacing need. Cumulative all-cause mortality was 21.7%. CONCLUSIONS: In the largest prospective study of the S-ICD to date, all study endpoints were met, despite a cohort with more comorbidities than in most previous trials. Complication rates were low and shock efficacy was high. These results demonstrate the 5-year S-ICD safety and efficacy for a large, diverse cohort of S-ICD recipients. (Subcutaneous Implantable Cardioverter-Defibrillator [S-ICD] System Post Approval Study [PAS]; NCT01736618).

Quality of life after the initial treatment of atrial fibrillation with cryoablation versus drug therapy.

BACKGROUND: The STOP AF First trial recently demonstrated that initial treatment with cryoballoon ablation (CBA) is safe and superior to antiarrhythmic drug (AAD) therapy for preventing atrial arrhythmia recurrence in patients with symptomatic atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to evaluate the change in quality of life (QoL) and symptoms after first-line CBA vs AAD therapy. METHODS: Patients with symptomatic AF not previously receiving rhythm control therapy were randomized to AAD (class I or III) or CBA (Arctic Front Advance, Medtronic, Mounds View, MN). QoL was evaluated at baseline and at 6 and 12 months by using the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and the European Quality of Life-5 Dimensions questionnaires. A review of AF-associated symptoms was conducted at baseline and at 1, 3, 6, and 12 months. RESULTS: In total, 203 subjects received either CBA (n = 104 [51.2%]) or AAD therapy (n = 99 [48.8%]). Improvements in the AFEQT summary and subscale scores were significantly larger with CBA than with AAD therapy at 6 and 12 months (P < .02 for all). Clinically meaningful improvement (>5 points) in the AFEQT summary score from baseline to 12 months was observed in 96.0% (100) of patients in the CBA arm vs 72.2% (71) of patients in the AAD arm (P < .001). No significant between-group differences were observed in the change in the European Quality of Life-5 Dimensions index or visual analog scale scores. Overall, 54.4% (57) of the CBA group vs 29.7% (29) of the AAD group reported no AF-specific symptom recurrence after a 90-day blanking period (P = .0005). CONCLUSION: First-line CBA vs AAD therapy is associated with larger improvements in AF-specific QoL and a higher rate of symptom resolution.

Machine Learning of 12-Lead QRS Waveforms to Identify Cardiac Resynchronization Therapy Patients With Differential Outcomes.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves heart failure outcomes but has significant nonresponse rates, highlighting limitations in ECG selection criteria: QRS duration (QRSd) ≥150 ms and subjective labeling of left bundle branch block (LBBB). We explored unsupervised machine learning of ECG waveforms to identify CRT subgroups that may differentiate outcomes beyond QRSd and LBBB. METHODS: We retrospectively analyzed 946 CRT patients with conduction delay. Principal component analysis (PCA) dimensionality reduction obtained a 2-dimensional representation of preCRT 12-lead QRS waveforms. k-means clustering of the 2-dimensional PCA representation of 12-lead QRS waveforms identified 2 patient subgroups (QRS PCA groups). Vectorcardiographic QRS area was also calculated. We examined following 2 primary outcomes: (1) composite end point of death, left ventricular assist device, or heart transplant, and (2) degree of echocardiographic left ventricular ejection fraction (LVEF) change after CRT. RESULTS: Compared with QRS PCA Group 2 (n=425), Group 1 (n=521) had lower risk for reaching the composite end point (HR, 0.44 [95% CI, 0.38-0.53]; P<0.001) and experienced greater mean LVEF improvement (11.1±11.7% versus 4.8±9.7%; P<0.001), even among patients with LBBB with QRSd ≥150 ms (HR, 0.42 [95% CI, 0.30-0.57]; P<0.001; mean LVEF change 12.5±11.8% versus 7.3±8.1%; P=0.001). QRS area also stratified outcomes but had significant differences from QRS PCA groups. A stratification scheme combining QRS area and QRS PCA group identified patients with LBBB with similar outcomes to non-LBBB patients (HR, 1.32 [95% CI, 0.93-1.62]; difference in mean LVEF change: 0.8% [95% CI, -2.1% to 3.7%]). The stratification scheme also identified patients with LBBB with QRSd <150 ms with comparable outcomes to patients with LBBB with QRSd ≥150 ms (HR, 0.93 [95% CI, 0.67-1.29]; difference in mean LVEF change: -0.2% [95% CI, -2.7% to 3.0%]). CONCLUSIONS: Unsupervised machine learning of ECG waveforms identified CRT subgroups with relevance beyond LBBB and QRSd. This method may assist in objective classification of bundle branch block morphology in CRT.

Outcomes of subcutaneous implantable cardioverter-defibrillator in dialysis patients: Results from the S-ICD post-approval study.

BACKGROUND: Patients with chronic renal disease on hemodialysis (HD) have limited vascular access and are at high risk of bacteremia. The subcutaneous implantable cardioverter-defibrillator (S-ICD) avoids vascular access, so it may be advantageous in this patient population. OBJECTIVE: The purpose of this study was to report outcomes of patients with end-stage renal disease enrolled in the multicenter S-ICD post-approval study (PAS). METHODS: S-ICD PAS patients were stratified on the basis of the presence (group 1) or absence (group 2) of HD at the time of implantation. Baseline demographic and clinical characteristics were collected. Perioperative and intermediate-term outcomes 365 days postimplantation were compared between the 2 groups. RESULTS: There were 220 patients on HD (13.4%) at the time of implantation out of 1637 patients enrolled in the S-ICD PAS. Patients on HD (group 1) were older (57.4 ± 13.2 years vs 52.5 ± 15.2 years; P < .0001), more likely to be of African descent (48.6% vs 25.1%; P < .0001), and had lower ejection fraction (28.6% ± 11.3% vs 32.6% ± 14.9%; P < .0001) as compared with patients not on HD (group 2). Group 1 had more comorbidities and mortality was higher (17.4% vs 3.7%) than did group 2. The rate of complications calculated using the Kaplan-Meier estimate did not differ between the 2 groups (overall P = .9169), with a 1-year rate of 7.9% and 7.7% for groups 1 and 2, respectively. The rate of appropriate shocks was significantly higher in group 1 (Kaplan-Meier analysis, P = .0003), as was inappropriate shocks (P = .0137). CONCLUSION: S-ICD is associated with similar adverse event rates but a higher risk of inappropriate and appropriate therapy in dialysis patients than in nondialysis patients.

Cardiac venous injuries: Procedural profiles and outcomes during left ventricular lead placement for cardiac resynchronization therapy.

BACKGROUND: Injury to the cardiac venous structures can complicate left ventricular lead placement for cardiac resynchronization therapy (CRT). Little is known about the outcomes of coronary sinus (CS) dissection with or without perforation. OBJECTIVE: The purpose of this study was to determine the outcomes in patients who had a CS injury during CRT implantation. METHODS: All patients undergoing procedures for CRT implantation at the Cleveland Clinic (2001-2018) were enrolled in a prospectively maintained registry for procedural profiles and complications. All patients with cardiac venous injuries during the procedures were included. RESULTS: CS injury occurred in 35 of 5011 patients (0.7%; 6 perforations (17.1%), 29 dissections without perforation (82.9%)). In patients with dissection in the absence of perforation, attempts at CS lead placement after dissection were successful in 21 of 29 patients (72.4%). In those with perforation (n=6, 17.1%), CS lead placement was successful in one of them (16.7%). Cardiac tamponade occurred in 2 patients (5.7%), and the procedure was aborted in both of them. Overall, CS lead placement failed in 13 patients (37%) but 9 (25.7%) underwent subsequent CRT with CS lead placement (n=6, 17.1%; median 58 days later) or epicardial leads (n=3, 8.6%). Three of the remaining 4 patients (8.6%) refused to undergo further procedures, and the fourth (2.9%) died of a complicated course. CONCLUSION: CS injury is not common during CRT implantation procedures and did not preclude successful lead placement in 23 of 35 patients (65.7%) during the index procedure and 6 of 6 (100%) during the subsequent attempted procedures. A low rate of mortality was observed in such patients, but CS injury was associated with increased morbidity.