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.

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.

Association Between Leukocyte Telomere Length and the Risk of Incident Atrial Fibrillation: The Framingham Heart Study.

BACKGROUND: Advancing age is a prominent risk factor for atrial fibrillation (AF). Shorter telomere length is a biomarker of biological aging, but the link between shorter telomere length and increased risk of AF remains unclear. We examined the association between shorter leukocyte telomere length (LTL) and incident AF. METHODS AND RESULTS: We included AF-free participants from the observational Framingham Heart Study Offspring cohort from 1995 to 1998, who had LTL measurements. We examined the association between baseline LTL and incident AF with multivariable Cox models adjusted for age, sex, current smoking, height, weight, systolic and diastolic blood pressure, use of antihypertensive medication, diabetes mellitus, history of myocardial infarction, and history of heart failure. The study sample comprised 1143 AF-free participants (52.8% women), with mean age of 60±8 years. The mean LTL at baseline was 6.95±0.57 kb. During 15.1±4.2 years mean follow-up, 184 participants (64 women) developed AF. Chronological age was associated with increased risk of AF (hazard ratio per 10-year increase, 2.16; 95% confidence interval, 1.71-2.72). There was no significant association between LTL and incident AF (hazard ratio per 1 SD decrease LTL, 1.01; 95% confidence interval, 0.86-1.19). Our study was observational in nature; hence, we could not exclude residual confounding and we were unable to establish causal pathways. CONCLUSIONS: In our moderate-sized community-based cohort, we did not find evidence for a significant association between LTL and risk of incident AF.

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.

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.

Physiology of biventricular pacing.

Biventricular pacing (cardiac resynchronization therapy ) has been shown to be a very effective therapy for patients with heart failure and dyssynchrony, with improved survival now shown in a recent trial. Electrical dyssynchrony, usually quantified by the duration of the QRS complex, is distinct from mechanical dyssynchrony. Intraventricular mechanical dyssynchrony is most commonly manifest by decreased septal work with concomitant early lateral wall prestretch and subsequent inefficient late contraction. Intraventricular dyssynchrony appears to be more predictive of response to CRT than interventricular dyssynchrony. Mechanical left ventricular dyssynchrony also is associated with regional molecular derangements in connexin-43, stress response kinases, and tumor necrosis factor-alpha. These molecular derangements may lead to abnormalities in conduction velocity and action potential duration, which may predispose to ventricular arrhythmia. Biventricular pacing corrects abnormal regional wall stresses and results in electrical, mechanical, and molecular left ventricular remodeling.