Contemporary trends in incident ischemic stroke, intracranial hemorrhage, and mortality in individuals with atrial fibrillation.

BACKGROUND: The prognosis for atrial fibrillation (AF) patients is based on data that is decades old. Given evolving standards of clinical practice, we sought to evaluate temporal trends in clinically important outcomes among patients with AF. METHODS: California's Department of Health Care Access and Information databases were used to identify adults aged ≥ 18 years with AF receiving hospital-based care in California. We compared 3 time-periods: 2005-2009, 2010-2014, and 2015-2019. ICD codes were used to identify chronic diseases and acute events. The outcomes were incident ischemic stroke, intracranial hemorrhage, and overall mortality. RESULTS: We included 2 009 832 patients with AF (52.7% males, 70.7% Whites, and mean age of 75.0 years), divided in 3 cohorts: 2005-2009 (n = 738 954), 2010-2014 (n = 609 447), and 2015-2019 (n = 661 431). Each outcome became substantially less common with time: compared to 2005-2009, AF patients diagnosed in 2015-2019 experienced a 34% (adjusted hazard ratio [HR] 0.66, 95% CI 0.64-0.69), 22% (HR 0.78, 0.75-0.82), and 24% (HR 0.76, 0.75-0.77) reduction in risk of incident ischemic stroke, intracranial hemorrhage, and mortality, respectively. Between 2005-2009 and 2015-2019, patients aged ≥ 65 years experienced more reductions in each outcome compared to younger patients (p < 0.001 for all), and declines in each outcome were significantly lower for Hispanics and Blacks compared to white patients. CONCLUSION: The risks of stroke, intracranial hemorrhage, and death have significantly declined among AF patients, although differences in the magnitude of improvement of these outcomes by demographic groups were observed. Commonly described estimates of the prognosis for AF patients should be updated to reflect contemporary care.

Systemic infarcts among patients with atrial fibrillation.

BACKGROUND: The epidemiology of atrial fibrillation (AF)-associated thromboembolic complications outside of ischemic strokes has not been thoroughly elucidated. OBJECTIVE: The aim of this study was to describe the epidemiology of AF-associated systemic infarcts and relevant interactions by sex and race/ethnicity. METHODS: Using the Office of Statewide Health Planning and Development, we performed a longitudinal analysis of patients aged ≥18 years who received ambulatory surgery, emergency, or inpatient medical care in California between 2005 and 2015. We determined the distribution of infarct locations and risks of systemic infarcts for patients with AF. Interaction analyses by sex and race/ethnicity were conducted. RESULTS: Of 1,321,694 patients with AF, the average annual rate of systemic infarct was 2.1% ± 0.18% compared with 0.56% ± 0.06% in the 22,944,488 patients without AF. The increased frequency of these infarcts was observed for every body area investigated. After adjustment for potential confounders and mediators, patients with AF experienced a 45% increased risk of a systemic infarct (hazard ratio, 1.45; 95% confidence interval, 1.44-1.47; P < .001). Women, Asians, Blacks, and Hispanics each exhibited a statistically significant heightened relative risk of systemic infarcts in the presence of AF. CONCLUSION: AF increases the risk of infarcts throughout the body. Susceptibility to these systemic infarcts varies by sex and race/ethnicity in patterns similar to differential risks for stroke. The presence of a systemic infarct in the absence of a clear cause should raise suspicion for AF, and the potential benefits of AF prevention and anticoagulation should be considered beyond only infarcts to the brain.

Patient-Level Artificial Intelligence-Enhanced Electrocardiography in Hypertrophic Cardiomyopathy: Longitudinal Treatment and Clinical Biomarker Correlations.

BACKGROUND: Artificial intelligence (AI) applied to 12-lead electrocardiographs (ECGs) can detect hypertrophic cardiomyopathy (HCM). OBJECTIVES: The purpose of this study was to determine if AI-enhanced ECG (AI-ECG) can track longitudinal therapeutic response and changes in cardiac structure, function, or hemodynamics in obstructive HCM during mavacamten treatment. METHODS: We applied 2 independently developed AI-ECG algorithms (University of California-San Francisco and Mayo Clinic) to serial ECGs (n = 216) from the phase 2 PIONEER-OLE trial of mavacamten for symptomatic obstructive HCM (n = 13 patients, mean age 57.8 years, 69.2% male). Control ECGs from 2,600 age- and sex-matched individuals without HCM were obtained. AI-ECG output was correlated longitudinally to echocardiographic and laboratory metrics of mavacamten treatment response. RESULTS: In the validation cohorts, both algorithms exhibited similar performance for HCM diagnosis, and exhibited mean HCM score decreases during mavacamten treatment: patient-level score reduction ranged from approximately 0.80 to 0.45 for Mayo and 0.70 to 0.35 for USCF algorithms; 11 of 13 patients demonstrated absolute score reduction from start to end of follow-up for both algorithms. HCM scores were significantly associated with other HCM-relevant parameters, including left ventricular outflow tract gradient at rest, postexercise, and with Valsalva, and NT-proBNP level, independent of age and sex (all P < 0.01). For both algorithms, the strongest longitudinal correlation was between AI-ECG HCM score and left ventricular outflow tract gradient postexercise (slope estimate: University of California-San Francisco 0.70 [95% CI: 0.45-0.96], P < 0.0001; Mayo 0.40 [95% CI: 0.11-0.68], P = 0.007). CONCLUSIONS: AI-ECG analysis longitudinally correlated with changes in echocardiographic and laboratory markers during mavacamten treatment in obstructive HCM. These results provide early evidence for a potential paradigm for monitoring HCM therapeutic response.

A Randomized Trial of High vs Standard Power Radiofrequency Ablation for Pulmonary Vein Isolation: SHORT-AF.

BACKGROUND: High-power, short duration (HPSD) radiofrequency ablation (RFA) is a commonly used strategy for pulmonary vein isolation (PVI). OBJECTIVES: This study sought to compare HPSD with standard power, standard duration (SPSD) RFA in patients undergoing PVI. METHODS: Patients with paroxysmal or persistent (<1 year) atrial fibrillation (AF) were randomized to HPSD (50 W) or SPSD (25-30 W) RFA to achieve PVI. Outcomes assessed included time to achieve PVI (primary), left atrial dwell time, total procedure time, first-pass isolation, PV reconnection with adenosine, procedure complications including asymptomatic cerebral emboli (ACE), and freedom from atrial arrhythmias. RESULTS: Sixty patients (median age 66 years; 75% male) with paroxysmal (57%) or persistent (43%) AF were randomized to HPSD (n = 29) or SPSD (n = 31). Median time to achieve PVI was shorter with HPSD vs SPSD (87 minutes vs 126 minutes; P = 0.003), as was left atrial dwell time (157 minutes vs 180 minutes; P = 0.04). There were no differences in first-pass isolation (79% vs 76%; P = 0.65) or PV reconnection with adenosine (12% vs 20%; P = 0.26) between groups. At 12 months, recurrent atrial arrhythmias occurred less in the HPSD group compared with the SPSD group (n = 3 of 29 [10%] vs n = 11 of 31 [35%]; HR: 0.26; P = 0.027). There was a trend toward more ACE with HPSD RFA (40% HPSD vs 17% SPSD; P = 0.053). CONCLUSIONS: In patients undergoing AF ablation, HPSD compared with SPSD RFA results in shorter time to achieve PVI, greater freedom from AF at 12 months, and a trend toward increased ACE.

The Value of Programmed Ventricular Extrastimuli From the Right Ventricular Basal Septum During Supraventricular Tachycardia.

BACKGROUND: The difference between the right ventricular (RV) apical stimulus-atrial electrogram (SA) interval during resetting of supraventricular tachycardia (SVT) versus the ventriculoatrial (VA) interval during SVT (ΔSA-VAapex) is an established technique for discerning SVT mechanisms but is limited by a significant diagnostic overlap. OBJECTIVES: This study hypothesized that the difference between the RV SA interval during resetting of SVTs versus the VA interval during SVTs (ΔSA-VA) would yield a more robust differentiation of atrioventricular nodal re-entrant tachycardia (AVNRT) from atrioventricular reciprocating tachycardia (AVRT) when using the RV basal septal stimulation (ΔSA-VAbase) as compared to the RV apical stimulation (ΔSA-VAapex). Moreover, it was predicted that the ΔSA-VAbase might distinguish septal from free wall accessory pathways (APs) effectively. METHODS: In this prospective study, 105 patients with AVNRTs (age 48 ± 20 years, 44% male) and 130 with AVRTs (age 26 ± 18 years, 54% male) underwent programmed ventricular extrastimuli delivered from both the RV basal septum and RV apex. The ΔSA-VA values were compared between the 2 sites. RESULTS: The ΔSA-VAbase was shorter than the ΔSA-VAapex during AVRT (44 ± 30 ms vs 58 ± 29 ms; P < 0.001), and the opposite occurred during AVNRT (133 ± 31 ms vs 125 ± 25 ms; P = 0.03). A ΔSA-VAbase of ≧85 milliseconds had a sensitivity of 97% and specificity of 96% for identifying AVNRT. Furthermore, a ΔSA-VAbase of 45-85 milliseconds identified AVRT with left free wall APs (sensitivity 86%, specificity 95%), 20-45 milliseconds for posterior septal APs (sensitivity 72%, specificity 96%), and <20 milliseconds for right free wall or anterior/mid septal APs (sensitivity 86%, specificity 98%). CONCLUSIONS: The ΔSA-VAbase during programmed ventricular extrastimuli produced a robust differentiation between AVNRT and AVRT regardless of the AP location with ≧85 milliseconds as an excellent cutoff point. This straightforward technique further allowed localizing 4 general AP sites.

Randomized Comparison of a Radiofrequency Wire Versus a Radiofrequency Needle System for Transseptal Puncture.

BACKGROUND: Transseptal puncture is a necessary component of many electrophysiology and structural heart procedures. Improving this technique has broad ramifications for the overall efficiency and safety of these interventions. A new technology uses a specialized introducer wire to cross the septum with radiofrequency (RF) energy, eliminating the need for a transseptal needle and wire/needle exchanges. OBJECTIVES: This study sought to compare the efficacy and safety of an RF needle versus RF wire approach for transseptal puncture. METHODS: Individuals ≥18 years of age undergoing double transseptal puncture for atrial fibrillation or left atrial flutter ablation were randomized to a transseptal approach with either an RF needle or RF wire. The primary outcome was time to achieve first transseptal puncture. Secondary outcomes included second and combined transseptal puncture time, fluoroscopy time, number of equipment exchanges, and complications. RESULTS: A total of 75 participants were enrolled (36 RF needle, 39 RF wire). No crossovers occurred. Randomization to the RF wire resulted in a significant reduction in first transseptal time compared with the RF needle (median 9.2 [IQR: 5.7-11.2] minutes vs 6.9 [IQR: 5.2-8.4] minutes, P = 0.03). Second and combined transseptal times, and number of equipment exchanges, were also reduced with the RF wire. One participant in the RF needle group experienced transient atrioventricular block due to mechanical trauma from the sheath/dilator assembly. There were no complications in the RF wire group. CONCLUSIONS: The RF wire technique resulted in faster time to transseptal puncture and fewer equipment exchanges compared with an RF needle with no difference in complications.

Combined pulsed field ablation with ultra-low temperature cryoablation: A preclinical experience.

BACKGROUND: Combining pulsed field ablation (PFA) with ultra-low temperature cryoablation (ULTC) represents a novel energy source which may create more transmural cardiac lesions. We sought to assess the feasibility of lesions created by combined cryoablation and pulsed field ablation (PFCA) versus PFA alone. METHODS: Ablations were performed using a custom PFA generator, ULTC console, and an ablation catheter with insertable stylets. PFA was delivered in a biphasic, bipolar train. PFCA precooled the tissue for 30 s followed by a concurrent PFA train. Benchtop testing using Schlieren imaging and microbubble volume assessment were used to compare PFA and PFCA. PFA and PFCA lesions using pre-optimized and optimized ablation protocols were studied in 6 swine. Pre and post-ECGs were recorded for each ablation and a gross necropsy was performed at 14 days. RESULTS: Consistent with benchtop comparisons of heat and microbubble generation, PFA deliveries in the animals were accompanied by muscle contractions and significant microbubbles (Grade 2-3) visible on intracardiac echo while neither occurred during PFCA at higher voltage levels. Both PFA and PFCA acutely eliminated or highly attenuated (>80%) local atrial electrograms. Histology of PFA and PFCA lesions indicated depth up to 6-7 mm and nearly all lesions were transmural. Optimized PFCA produced wider cavotricuspid isthmus lesions with evidence of tissue selectivity. CONCLUSION: A novel technology combining PFA and ULTC into one energy source demonstrated in-vivo feasibility for PFCA ablation. PFCA had a more favorable thermal profile and did not produce muscle contraction or microbubbles while extending lesion depth beyond cryoablation.

SARS-CoV-2 infection and cardiac arrhythmias.

Although cardiac arrhythmias have been observed and described during and after SARS-CoV-2 infection, rigorous studies designed to untangle the complex relationship between this proinflammatory illness and arrhythmogenesis are limited. Despite a pervasive opinion to the contrary, there is presently no definitive data to establish a causal, viral-specific association between COVID-19 and incident arrhythmia.

Cannabis, cocaine, methamphetamine, and opiates increase the risk of incident atrial fibrillation.

AIMS: Atrial fibrillation (AF) is now regarded as a preventable disease, requiring a search for modifiable risk factors. With legalization of cannabis and more lenient laws regarding the use of other illicit substances, investigation into the potential effects of methamphetamine, cocaine, opiate, and cannabis exposure on incident AF is needed. METHODS AND RESULTS: Using Office of Statewide Health Planning and Development databases, a longitudinal analysis was performed of adult Californians ≥18 years of age who received care in an emergency department, outpatient surgery facility, or hospital from 1 January 2005 to 31 December 2015. Associations between healthcare coding for the use of each substance and a new AF diagnosis were assessed. Among 23,561,884 patients, 98 271 used methamphetamine, 48 701 used cocaine, 10 032 used opiates, and 132 834 used cannabis. Of the total population, 998 747 patients (4.2%) developed incident AF during the study period. After adjusting for potential confounders and mediators, use of methamphetamines, cocaine, opiates, and cannabis was each associated with increased incidence of AF: hazard ratios 1.86 [95% confidence interval (CI) 1.81-1.92], 1.61 (95% CI 1.55-1.68), 1.74 (95% CI 1.62-1.87), and 1.35 (95% CI 1.30-1.40), respectively. Negative control analyses in the same cohort failed to reveal similarly consistent positive relationships. CONCLUSION: Methamphetamine, cocaine, opiate, and cannabis uses were each associated with increased risk of developing incident AF. Efforts to mitigate the use of these substances may represent a novel approach to AF prevention.

Prospective arrhythmia surveillance after a COVID-19 diagnosis.

BACKGROUND: Cardiac arrhythmias have been observed among patients hospitalised with acute COVID-19 infection, and palpitations remain a common symptom among the much larger outpatient population of COVID-19 survivors in the convalescent stage of the disease. OBJECTIVE: To determine arrhythmia prevalence among outpatients after a COVID-19 diagnosis. METHODS: Adults with a positive COVID-19 test and without a history of arrhythmia were prospectively evaluated with 14-day ambulatory electrocardiographic monitoring. Participants were instructed to trigger the monitor for palpitations. RESULTS: A total of 51 individuals (mean age 42±11 years, 65% women) underwent monitoring at a median 75 (IQR 34-126) days after a positive COVID-19 test. Median monitoring duration was 13.2 (IQR 10.5-13.8) days. No participant demonstrated atrial fibrillation, atrial flutter, sustained supraventricular tachycardia (SVT), sustained ventricular tachycardia or infranodal atrioventricular block. Nearly all participants (96%) had an ectopic burden of <1%; one participant had a 2.8% supraventricular ectopic burden and one had a 15.4% ventricular ectopic burden. While 47 (92%) participants triggered their monitor for palpitation symptoms, 78% of these triggers were for either sinus rhythm or sinus tachycardia. CONCLUSIONS: We did not find evidence of malignant or sustained arrhythmias in outpatients after a positive COVID-19 diagnosis. While palpitations were common, symptoms frequently corresponded to sinus rhythm/sinus tachycardia or non-malignant arrhythmias such as isolated ectopy or non-sustained SVT. While these findings cannot exclude the possibility of serious arrhythmias in select individuals, they do not support a strong or widespread proarrhythmic effect of COVID-19 infection after resolution of acute illness.

Premature ventricular complexes and development of heart failure in a community-based population.

OBJECTIVE: A higher premature ventricular complex (PVC) frequency is associated with incident congestive heart failure (CHF) and death. While certain PVC characteristics may contribute to that risk, the current literature stems from patients in medical settings and is therefore prone to referral bias. This study aims to identify PVC characteristics associated with incident CHF in a community-based setting. METHODS: The Cardiovascular Health Study is a cohort of community-dwelling individuals who underwent prospective evaluation and follow-up. We analysed 24-hour Holter data to assess PVC characteristics and used multivariable logistic and Cox proportional hazards models to identify predictors of a left ventricular ejection fraction (LVEF) decline and incident CHF, respectively. RESULTS: Of 871 analysed participants, 316 participants exhibited at least 10 PVCs during the 24-hour recording. For participants with PVCs, the average age was 72±5 years, 41% were women and 93% were white. Over a median follow-up of 11 years, 34% developed CHF. After adjusting for demographics, cardiovascular comorbidities, antiarrhythmic drug use and PVC frequency, a greater heterogeneity of the PVC coupling interval was associated with an increased risk of LVEF decline and incident CHF. Of note, neither PVC duration nor coupling interval duration exhibited a statistically significant relationship with either outcome. CONCLUSIONS: In this first community-based study to identify Holter-based features of PVCs that are associated with LVEF reduction and incident CHF, the fact that coupling interval heterogeneity was an independent risk factor suggests that the mechanism of PVC generation may influence the risk of heart failure.

Human Immunodeficiency Virus Infection and Out-of-Hospital Cardiac Arrest.

Patients with human immunodeficiency virus (HIV) infection are at increased risk of cardiovascular disease, but studies on HIV as a risk factor for cardiac arrest in the general population are lacking. We aimed to examine the association of HIV infection with out-of-hospital cardiac arrests (OHCAs). We used the Office of Statewide Health Planning and Development data to evaluate HIV infection as a predictor of OHCA in all California emergency department encounters from 2005 to 2015, adjusting for age, gender, race, income, obesity, smoking, alcohol, substance abuse, hypertension (HTN), diabetes, coronary artery disease, congestive heart failure (CHF), atrial fibrillation, and chronic kidney disease (CKD). We also determined patient characteristics modifying these associations by including interaction terms in multivariable-adjusted models. In 18,542,761 patients (mean age 47 ± 20 years, 53% women, 43,849 with HIV) followed for a median 6.8 years, 133,983 new OHCA events occurred. Incidence rates in patients with HIV were higher than in patients without HIV (1.99 vs 1.16 OHCA events per 1,000-person-years follow-up). After multivariable adjustment, HIV was associated with a 2.5-fold higher risk of OHCA (hazard ratio 2.47, 95% confidence interval 2.29 to 2.66, p <0.001). The risk of OHCA with HIV was disproportionately stronger in younger patients, women, and in those with HTN, CHF, and CKD. In this large prospective study, HIV was associated with a 2.5-fold increased risk of OHCA, with a greater vulnerability to this outcome in patients with HIV who were female or had HTN, CHF, or CKD.

Adaptive Cardiac Resynchronization Therapy Effect on Electrical Dyssynchrony (aCRT-ELSYNC): A randomized controlled trial.

BACKGROUND: Adaptive cardiac resynchronization therapy (aCRT) is known to have clinical benefits over conventional CRT, but the mechanisms are unclear. OBJECTIVE: Compare effects of aCRT and conventional CRT on electrical dyssynchrony. METHODS: A prospective, double-blind, 1:1 parallel-group assignment randomized controlled trial in patients receiving CRT for routine clinical indications. Participants underwent cardiac computed tomography and 128-electrode body surface mapping. The primary outcome was change in electrical dyssynchrony measured on the epicardial surface using noninvasive electrocardiographic imaging before and 6 months post-CRT. Ventricular electrical uncoupling (VEU) was calculated as the difference between the mean left ventricular (LV) and right ventricular (RV) activation times. An electrical dyssynchrony index (EDI) was computed as the standard deviation of local epicardial activation times. RESULTS: We randomized 27 participants (aged 64 ± 12 years; 34% female; 53% ischemic cardiomyopathy; LV ejection fraction 28% ± 8%; QRS duration 155 ± 21 ms; typical left bundle branch block [LBBB] in 13%) to conventional CRT (n = 15) vs aCRT (n = 12). In atypical LBBB (n = 11; 41%) with S waves in V5-V6, conduction block occurred in the anterior RV, as opposed to the interventricular groove in strict LBBB. As compared to baseline, VEU reduced post-CRT in the aCRT (median reduction 18.9 [interquartile range 4.3-29.2 ms; P = .034]), but not in the conventional CRT (21.4 [-30.0 to 49.9 ms; P = .525]) group. There were no differences in the degree of change in VEU and EDI indices between treatment groups. CONCLUSION: The effect of aCRT and conventional CRT on electrical dyssynchrony is largely similar, but only aCRT harmoniously reduced interventricular dyssynchrony by reducing RV uncoupling.

Arrhythmias Utilizing Concealed Nodoventricular or His-Ventricular Pathways: A Structured Approach to Diagnosis and Management.

OBJECTIVES: This study sought to describe the electrophysiologic characteristics, diagnostic maneuvers, and treatment of a series of arrhythmias using concealed nodoventricular (cNV) or His-ventricular (cHV) pathways. BACKGROUND: Confirming the presence and participation of cNV or cHV pathways in tachyarrhythmias is challenging. METHODS: We present 4 cases of tachycardias with a participatory cNV or cHV pathway. RESULTS: The first patient had a narrow complex tachycardia with ventriculoatrial dissociation. Findings of an entrainment pacing from the right ventricle and fused premature ventricular complexes suggested cNV pathway involvement. The second patient had nonsustained narrow complex tachycardia with more ventricular than atrial complexes. The tachycardia exhibited an anterograde His-right bundle (RB) activation sequence and normal His-ventricular (HV) interval and consistently terminated with fused ventricular extra stimuli, suggesting cNV pathway participation. The third patient had a wide complex tachycardia (WCT) with either a right or left bundle branch block pattern. The WCT showed an eccentric His-RB activation sequence and short HV interval and terminated with fused premature ventricular complexes, suggesting a cHV (or concealed fasciculoventricular) pathway involvement. The fourth patient had a WCT with alternating bundle branch block morphologies with a short HV interval. Entrainment from the basal right ventricle demonstrated fusion and a short postpacing interval, suggesting cHV (or fasciculoventricular) pathway involvement. Ablation at the proximal RB rendered the tachycardia noninducible. CONCLUSIONS: A structured approach can help diagnose and treat cNV or cHV pathways. We emphasize the importance of evaluating both the His-RB activation pattern and HV interval during sinus rhythm and tachycardia as well as the ventricular pacing study.