Mechanisms and management of inappropriate therapy in subcutaneous implantable cardioverter defibrillators.

Subcutaneous implantable cardioverter defibrillators (S-ICDs) provide reliable defibrillation and have enhanced supraventricular tachycardia discrimination and fewer infection rates compared with traditional transvenous systems. However, inappropriate shocks remain a frequent problem. Herein, we review the various mechanisms of these inappropriate therapies, some of which are unique to S-ICDs, and propose an algorithm for preventing recurrences. Proper screening of preimplants is essential to help minimize inappropriate therapies, but patients with hypertrophic cardiomyopathy, Brugada syndrome, and arrhythmogenic right ventricular cardiomyopathy are at particular risk and may require additional measures.

High impedance alert with safety switching: An unreported hazard of hybrid pacing systems.

Several Boston Scientific pacemaker models have a known issue with intermittent oversensing of the minute ventilation sensor when paired with non-Boston Scientific leads. Several of our patients with these hybrid systems have had transient out of range impedances and oversensing after safety switching which we suspected may be related. A retrospective analysis of 395 patients who had pacemakers implanted between 2015-2017 found that transient out of range impedances with safety switching was present in 9% of Boston Scientific pacemakers paired with Abbott or Medtronic leads compared with 0% in other device-lead combinations (P = 0.0089). We postulate that the root cause of the minute ventilation oversensing and transient high impedance issue is the same, a header-lead interaction from low-level incompatibility. Recognizing this issue is critical to prevent unnecessary lead revisions or extractions as it can be prevented with a simple reprogramming of lead pace/sense configuration.

Atrial Fibrillation: Epidemiology, Pathophysiology, and Clinical Outcomes.

The past 3 decades have been characterized by an exponential growth in knowledge and advances in the clinical treatment of atrial fibrillation (AF). It is now known that AF genesis requires a vulnerable atrial substrate and that the formation and composition of this substrate may vary depending on comorbid conditions, genetics, sex, and other factors. Population-based studies have identified numerous factors that modify the atrial substrate and increase AF susceptibility. To date, genetic studies have reported 17 independent signals for AF at 14 genomic regions. Studies have established that advanced age, male sex, and European ancestry are prominent AF risk factors. Other modifiable risk factors include sedentary lifestyle, smoking, obesity, diabetes mellitus, obstructive sleep apnea, and elevated blood pressure predispose to AF, and each factor has been shown to induce structural and electric remodeling of the atria. Both heart failure and myocardial infarction increase risk of AF and vice versa creating a feed-forward loop that increases mortality. Other cardiovascular outcomes attributed to AF, including stroke and thromboembolism, are well established, and epidemiology studies have championed therapeutics that mitigate these adverse outcomes. However, the role of anticoagulation for preventing dementia attributed to AF is less established. Our review is a comprehensive examination of the epidemiological data associating unmodifiable and modifiable risk factors for AF and of the pathophysiological evidence supporting the mechanistic link between each risk factor and AF genesis. Our review also critically examines the epidemiological data on clinical outcomes attributed to AF and summarizes current evidence linking each outcome with AF.

Retrieval of Embolized WATCHMAN® Flex Atrial Appendage Occlusion Device.

This case report documents the management of a 66-year old man with atrial fibrillation with recent placement of a WATCHMAN® Flex atrial appendage occlusion device. The patient presented with renal failure, abdominal pain, and difficulty walking 2 months after placement. The WATCHMAN® Flex device was found to have embolized to his abdominal aorta at the level of the renal arteries with associated thrombus. Extensive workup revealed reduced left ventricular cardiac function and decreased renal function, both of which were felt to be potentially reversible with device removal. The patient then underwent retrieval of the device and all associated thrombus via an open retroperitoneal approach. This case demonstrates a potential consequence of implanting devices such as an atrial appendage occlusion device and describes a technique for removal.

Cognitive impairment and treatment strategy for atrial fibrillation in older adults: The SAGE-AF study.

BACKGROUND: Cognitive impairment is strongly associated with atrial fibrillation (AF). Rate and rhythm control are the two treatment strategies for AF and the effect of treatment strategy on risk of cognitive decline and frailty is not well established. We sought to determine how treatment strategy affects geriatric-centered outcomes. METHODS: The Systematic Assessment of Geriatric Elements-AF (SAGE-AF) was a prospective, observational, cohort study. Older adults with AF were prospectively enrolled between 2016 and 2018 and followed longitudinally for 2 years. In a non-randomized fashion, participants were grouped by rate or rhythm control treatment strategy based on clinical treatment at enrollment. Baseline characteristics were compared. Longitudinal binary mixed models were used to compare treatment strategy with respect to change in cognitive function and frailty status. Cognitive function and frailty status were assessed with the Montreal Cognitive Assessment Battery and Fried frailty phenotype tools. RESULTS: 972 participants (mean age = 75, SD = 6.8; 49% female, 87% non-Hispanic white) completed baseline examination and 2-year follow-up. 408 (42%) were treated with rate control and 564 (58%) with rhythm control. The patient characteristics of the two groups were different at baseline. Participants in the rate control group were older, more likely to have persistent AF, prior stroke, be treated with warfarin and have baseline cognitive impairment. After adjusting for baseline differences, participants treated with rate control were 1.5 times more likely to be cognitively impaired over 2 years (adjusted OR: 1.47, 95% CI:1.12, 1.98) and had a greater decline in cognitive function (adjusted estimate: -0.59 (0.23), p < 0.01) in comparison to rhythm control. Frailty did not vary between the treatment strategies. CONCLUSIONS: Among those who had 2-year follow-up in non-randomized observational cohort, the decision to rate control AF in older adults was associated with increased odds of decline in cognitive function but not frailty.

Incidence and prognostic significance of newly-diagnosed atrial fibrillation among older U.S. veterans hospitalized with COVID-19.

Most prior studies on the prognostic significance of newly-diagnosed atrial fibrillation (AF) in COVID-19 did not differentiate newly-diagnosed AF from pre-existing AF. To determine the association between newly-diagnosed AF and in-hospital and 30-day mortality among regular users of Veterans Health Administration using data linked to Medicare. We identified Veterans aged ≥ 65 years who were hospitalized for ≥ 24 h with COVID-19 from 06/01/2020 to 1/31/2022 and had ≥ 2 primary care visits within 24 months prior to the index hospitalization. We performed multivariable logistic regression analyses to estimate adjusted risks, risk differences (RD), and odds ratios (OR) for the association between newly-diagnosed AF and the mortality outcomes adjusting for patient demographics, baseline comorbidities, and presence of acute organ dysfunction on admission. Of 23,299 patients in the study cohort, 5.3% had newly-diagnosed AF, and 29.2% had pre-existing AF. In newly-diagnosed AF adjusted in-hospital and 30-day mortality were 16.5% and 22.7%, respectively. Newly-diagnosed AF was associated with increased mortality compared to pre-existing AF (in-hospital: OR 2.02, 95% confidence interval [CI] 1.72-2.37; RD 7.58%, 95% CI 5.54-9.62) (30-day: OR 1.86; 95% CI 1.60-2.16; RD 9.04%, 95% CI 6.61-11.5) or no AF (in-hospital: OR 2.24, 95% CI 1.93-2.60; RD 8.40%, 95% CI 6.44-10.4) (30-day: 2.07, 95% CI 1.80-2.37; RD 10.2%, 95% CI 7.89-12.6). There was a smaller association between pre-existing AF and the mortality outcomes. Newly-diagnosed AF is an important prognostic marker for patients hospitalized with COVID-19. Whether prevention or treatment of AF improves clinical outcomes in these patients remains unknown.

Cognitive impairment, age, quality of life, and treatment strategy for atrial fibrillation in older adults: The SAGE-AF study.

BACKGROUND: Atrial fibrillation (AF) treatment includes anticoagulation for high stroke risk individuals and either rate or rhythm control strategies. We aimed to investigate the impact of age, geriatric factors, and medical comorbidities on choice of rhythm versus rate control strategy in older adults. METHODS: Patients with AF aged ≥65 years with CHA2 DS2 VASc score ≥2 and eligible for anticoagulation were recruited for the Systematic Assessment of Geriatric Elements-AF (SAGE-AF) prospective cohort study. An interview that included measures of HRQoL, cognitive function, vision, hearing, and frailty was performed. The association between these elements and AF treatment strategy was examined by multivariable logistic regression models. RESULTS: One thousand two hundred forty-four participants (mean age 76 years; 49% female; 85% non-Hispanic white) were enrolled. Rate and rhythm control were used in 534 and 710 participants, respectively. Compared to participants <75 years, those ≥75 were more likely to be treated with a rate control strategy (age 75-84 adjusted odds ratio [aOR] 1.37 [95% CI 0.99, 1.88]; age 85+ aOR = 2.05, 95% CI 1.30, 3.21). Those treated with a rate control strategy were more likely to have cognitive impairment (aOR = 1.50, 95% CI 1.13, 1.99), and peripheral vascular disease (PVD) (aOR = 1.82, 95% CI 1.22, 2.72) but less likely to have visual impairment (aOR 0.73 [0.55, 0.98]), congestive heart failure (CHF; aOR 0.68 [0.49, 0.94]) or receive anticoagulation (aOR 0.53, 95% CI 0.36, 0.78). CONCLUSION: Older age, cognitive impairment, and PVD were associated with use of rate control strategy. Visual impairment, CHF, and anticoagulation use were associated with a rhythm control strategy. There was no difference in HRQoL between the rate and rhythm control groups. This study suggests that certain geriatric elements may be associated with AF treatment strategies. Further study is needed to evaluate how these decisions affect outcomes.

Meta-Analysis of Randomized Clinical Trials Comparing the Impact of Implantable Loop Recorder Versus Usual Care After Ischemic Stroke for Detection of Atrial Fibrillation and Stroke Risk.

Implantable loop recorder (ILR) is recommended to detect subclinical atrial fibrillation (AF) after cryptogenic stroke; however, the clinical outcomes of this practice is unclear. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate 12-month AF detection, change in oral anticoagulation (OAC), and recurrent stroke in ILR versus usual care after ischemic stroke. We searched Medline, Embase, Web of Science, Cochrane Library for randomized controlled trials comparing ILR with usual care after any ischemic stroke. Primary outcomes were cumulative AF detection and recurrent stroke (ischemic or hemorrhagic) or transient ischemic attack over 12 months. Secondary outcome was OAC initiation. Meta-analysis was performed with Mantel-Haenszel pooled odds ratios (ORs) and random effects models. Of 200 identified articles, 3 trials were included (1,233 participants). Cryptogenic stroke and underlying AF included cryptogenic stroke only, stroke of known cause and underlying-AF included small or large vessel stroke only, and post embolic rhythm detection with implantable vs external monitoring included all ischemic strokes. The 12-month AF detection was 13% in the ILR group and 2.4% in controls. ILR was more likely to detect AF compared with usual care (OR 5.8, 95% confidence interval 3.2 to 10.2). Stroke or transient ischemic attack occurred in 7% with ILR and 9% with usual care (OR 0.8, 95% confidence interval 0.5 to 1.2). In patients with detected AF, 97% and 100% were started on OAC in cryptogenic stroke and underlying AF and post embolic rhythm detection with implantable vs external monitoring, respectively, compared with 68% in stroke of known cause and underlying-AF. In conclusion, ILR was superior to usual care in AF detection, but the relative low incidence of AF and the nondifferential risk of stroke between the ILR and usual care arms may suggest that most patients do not benefit from ILR implantation. Further studies are warranted to understand if patient selection can be improved to increase the diagnostic yield of ILR.

Sex-Specific Prevalence, Incidence, and Mortality Associated With Atrial Fibrillation in Heart Failure.

OBJECTIVES: This study sought to investigate the mortality associated with atrial fibrillation (AF) in men and women with heart failure (HF) according to the sequence of presentation and rhythm versus rate control. BACKGROUND: The sex-specific epidemiology of AF in HF is sparse. METHODS: Using the Danish nationwide registries, all first-time cases of HF were identified and followed for all-cause mortality from 1998 to 2018. RESULTS: Among 252,988 patients with HF (mean age: 74 ± 13 years, 45% women), AF presented before HF in 54,064 (21%) and on the same day in 27,651 (11%) individuals, similar in women and men. Among patients without AF, the cumulative 10-year incidence of AF was 18.7% (95% confidence interval [CI]: 18.2% to 19.1%) in women and 21.3% (95% CI: 21.0% to 21.6%) in men. On follow-up (mean: 6.2 ± 5.8 years), adjusted mortality rate ratios were 3.33 (95% CI: 3.25 to 3.41) in women and 2.84 (95% CI: 2.78 to 2.90) in men if AF antedated HF, 3.45 (95% CI: 3.37 to 3.56) in women versus 2.76 (95% CI: 2.69 to 2.83) in men when AF and HF were diagnosed concomitantly, and 4.85 (95% CI: 4.73 to 4.97) in women versus 3.89 (95% CI: 3.80 to 3.98) in men when AF developed after HF. Compared with rate control for AF, a rhythm-controlling strategy was associated with lowered mortality in inverse probability-weighted models across all strata and in both sexes (hazard ratio: 0.75 to 0.83), except for women who developed AF after HF onset (hazard ratio: 1.03). CONCLUSIONS: More than half of all men and women with HF will develop AF during their clinical course, with prognosis associated with AF being worse in women than men. Further studies are needed to understand the underlying mechanisms.

Reversal of global apoptosis and regional stress kinase activation by cardiac resynchronization.

BACKGROUND: Cardiac dyssynchrony in the failing heart worsens global function and efficiency and generates regional loading disparities that may exacerbate stress-response molecular signaling and worsen cell survival. We hypothesized that cardiac resynchronization (CRT) from biventricular stimulation reverses such molecular abnormalities at the regional and global levels. METHODS AND RESULTS: Adult dogs (n=27) underwent left bundle-branch radiofrequency ablation, prolonging the QRS by 100%. Dogs were first subjected to 3 weeks of atrial tachypacing (200 bpm) to induce dyssynchronous heart failure (DHF) and then randomized to either 3 weeks of additional atrial tachypacing (DHF) or biventricular tachypacing (CRT). At 6 weeks, ejection fraction improved in CRT (2.8+/-1.8%) compared with DHF (-4.4+/-2.7; P=0.02 versus CRT) dogs, although both groups remained in failure with similarly elevated diastolic pressures and reduced dP/dtmax. In DHF, mitogen-activated kinase p38 and calcium-calmodulin-dependent kinase were disproportionally expressed/activated (50% to 150%), and tumor necrosis factor-alpha increased in the late-contracting (higher-stress) lateral versus septal wall. These disparities were absent with CRT. Apoptosis assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining, caspase-3 activity, and nuclear poly ADP-ribose polymerase cleavage was less in CRT than DHF hearts and was accompanied by increased Akt phosphorylation/activity. Bcl-2 and BAD protein diminished with DHF but were restored by CRT, accompanied by marked BAD phosphorylation, enhanced BAD-14-3-3 interaction, and reduced phosphatase PP1alpha, consistent with antiapoptotic effects. Other Akt-coupled modulators of apoptosis (FOXO-3alpha and GSK3beta) were more phosphorylated in DHF than CRT and thus less involved. CONCLUSIONS: CRT reverses regional and global molecular remodeling, generating more homogeneous activation of stress kinases and reducing apoptosis. Such changes are important benefits from CRT that likely improve cardiac performance and outcome.

Magnetic resonance-based anatomical analysis of scar-related ventricular tachycardia: implications for catheter ablation.

In catheter ablation of scar-related monomorphic ventricular tachycardia (VT), substrate voltage mapping is used to electrically define the scar during sinus rhythm. However, the electrically defined scar may not accurately reflect the anatomical scar. Magnetic resonance-based visualization of the scar may elucidate the 3D anatomical correlation between the fine structural details of the scar and scar-related VT circuits. We registered VT activation sequence with the 3D scar anatomy derived from high-resolution contrast-enhanced MRI in a swine model of chronic myocardial infarction using epicardial sock electrodes (n=6, epicardial group), which have direct contact with the myocardium where the electrical signal is recorded. In a separate group of animals (n=5, endocardial group), we also assessed the incidence of endocardial reentry in this model using endocardial basket catheters. Ten to 12 weeks after myocardial infarction, sustained monomorphic VT was reproducibly induced in all animals (n=11). In the epicardial group, 21 VT morphologies were induced, of which 4 (19.0%) showed epicardial reentry. The reentry isthmus was characterized by a relatively small volume of viable myocardium bound by the scar tissue at the infarct border zone or over the infarct. In the endocardial group (n=5), 6 VT morphologies were induced, of which 4 (66.7%) showed endocardial reentry. In conclusion, MRI revealed a scar with spatially complex structures, particularly at the isthmus, with substrate for multiple VT morphologies after a single ischemic episode. Magnetic resonance-based visualization of scar morphology would potentially contribute to preprocedural planning for catheter ablation of scar-related, unmappable VT.

Pathophysiological mechanisms underlying ventricular dyssynchrony.

Left ventricular dyssynchrony due to conduction system disease creates cardiac inefficiency even in normal hearts. Dyssynchrony in the failing heart results in the development of a discrete heart failure phenotype as it induces chamber heterogeneity at the cellular and molecular levels that leads to impaired excitation-contraction coupling, increased arrhythmia susceptibility, and decreased myocyte survival among other pathologic changes. Recent research has demonstrated that these biomolecular changes are amazingly reversed with cardiac resynchronization therapy, providing insight into how to target the therapy.

Differential effective refractory period as a useful marker of multiple accessory pathways.

Accessory pathway (AP) ablation failure may be related to multiple pathways which go unrecognized at the time of electrophysiology study. We present a patient who had two adjacent APs based on different preexcitation patterns as well as effective refractory periods (ERPs) which have not been previously described. Apart from leading to recurrent supraventricular tachycardia (SVT), multiple pathways are important to recognize as they more frequently predispose to malignant atrial arrhythmias.

Epidemiology of Atrial Fibrillation and Heart Failure: A Growing and Important Problem.

The global prevalence of atrial fibrillation (AF) and heart failure (HF) is rising. Population-based studies have observed that AF and HF often coexist, predispose to each other, and share risk factors. Age is the most potent risk factor for both AF and HF, but race plays an important role. Although AF and HF share common risk factors, adjusting for these risk factors does not explain the higher risk of AF patients developing HF and vice versa. Common pathophysiologic mechanisms may explain this linkage. The morbidity and mortality outcomes with combined AF and HF are substantial and warrant improved preventive strategies.

Gastrointestinal and liver diseases and atrial fibrillation: a review of the literature.

Atrial fibrillation (AF) is the most common arrhythmia worldwide and is associated with significant morbidity and mortality. A number of risk factors have been associated with AF, though few studies have explored the association between gastrointestinal and liver diseases and AF. Additionally, AF and treatment for AF may predispose to gastrointestinal and liver diseases. We review the current literature on the bidirectional associations between gastrointestinal and liver diseases and AF. We highlight the gaps in knowledge and areas requiring future investigation.

Three-dimensional mapping of optimal left ventricular pacing site for cardiac resynchronization.

BACKGROUND: The efficacy of cardiac resynchronization therapy (CRT) depends on placement of the left ventricular lead within the late-activated territory. The geographic extent and 3-dimensional distribution of left ventricular (LV) locations yielding optimal CRT remain unknown. METHODS AND RESULTS: Normal or tachypacing-induced failing canine hearts made dyssynchronous by right ventricular free wall pacing or chronic left bundle-branch ablation were acutely instrumented with a nonconstraining epicardial elastic sock containing 128 electrodes interfaced with a computer-controlled stimulation/recording system. Biventricular CRT was performed using a fixed right ventricular site and randomly selected LV sites covering the entire free wall. For each LV site, global cardiac function (conductance catheter) and mechanical synchrony (magnetic resonance imaging tagging) were determined to yield 3-dimensional maps reflecting CRT impact. Optimal CRT was achieved from LV lateral wall sites, slightly more anterior than posterior and more apical than basal. LV sites yielding > or = 70% of the maximal dP/dtmax increase covered approximately 43% of the LV free wall. This distribution and size were similar in both normal and failing hearts. The region was similar for various systolic and diastolic parameters and correlated with 3-dimensional maps based on mechanical synchrony from magnetic resonance imaging strain analysis. CONCLUSIONS: In hearts with delayed lateral contraction, optimized CRT is achieved over a fairly broad area of LV lateral wall in both nonfailing and failing hearts, with modest anterior or posterior deviation still capable of providing effective CRT. Sites selected to achieve the most mechanical synchrony are generally similar to those that most improve global function, confirming a key assumption underlying the use of wall motion analysis to optimize CRT.

Cardiac magnetic resonance assessment of mechanical dyssynchrony.

PURPOSE OF REVIEW: Echocardiographic techniques have played a major role in the assessment of mechanical dyssynchrony and the selection of patients for cardiac resynchronization therapy. The accuracy and reliability of such measures, however, have recently been placed under great scrutiny. This has shifted interest to cardiovascular magnetic resonance as an alternative method to assess myocardial dyssynchrony but these methods are relatively underdeveloped and not used widely clinically. Accordingly, the purpose of this review is to highlight existing and emerging CMR acquisition methods for quantifying dyssynchrony as well as the potential role of CMR to improve patient selection for CRT. RECENT FINDINGS: CMR has a number of advantages over current echocardiographic methods for the assessment of myocardial dyssynchrony including quantitative assessment of circumferential strain and myocardial scar burden and distribution. Recent studies also demonstrate the ability to perform CMR in patients with CRT devices. SUMMARY: CMR assessment of myocardial dyssynchrony is a logical alternative to echocardiographic based methods that provides highly quantitative and reproducible data sets of function and scar that are predictive of CRT response. The future ability to perform CMR imaging in patients pre-CRT and post-CRT may for the first time allow full characterization of CRT response.