Atrial fibrillation: the role of hypoxia-inducible factor-1-regulated cytokines.

Atrial fibrillation (AF) is a common arrhythmia that has major morbidity and mortality. Hypoxia plays an important role in AF initiation and maintenance. Hypoxia-inducible factor (HIF), the master regulator of oxygen homeostasis in cells, plays a fundamental role in the regulation of multiple chemokines and cytokines that are involved in different physiological and pathophysiological pathways. HIF is also involved in the pathophysiology of AF induction and propagation mostly through structural remodeling such as fibrosis; however, some of the cytokines discussed have even been implicated in electrical remodeling of the atria. In this article, we highlight the association between HIF and some of its related cytokines with AF. Additionally, we provide an overview of the potential diagnostic benefits of using the mentioned cytokines as AF biomarkers. Research discussed in this review suggests that the expression of these cytokines may correlate with patients who are at an increased risk of developing AF. Furthermore, cytokines that are elevated in patients with AF can assist clinicians in the diagnosis of suspect paroxysmal AF patients. Interestingly, some of the cytokines have been elevated specifically when AF is associated with a hypercoagulable state, suggesting that they could be helpful in the clinician's and patient's decision to begin anticoagulation. Finally, more recent research has demonstrated the promise of targeting these cytokines for the treatment of AF. While still in its early stages, tools such as neutralizing antibodies have proved to be efficacious in targeting the HIF pathway and treating or preventing AF.

Subclinical atrial fibrillation detection with a floating atrial sensing dipole in single lead implantable cardioverter-defibrillator systems: Results of the SENSE trial.

INTRODUCTION: Subclinical atrial fibrillation (AF), in the form of cardiac implantable device-detected atrial high rate episodes (AHREs), has been associated with increased thromboembolism. An implantable cardioverter-defibrillator (ICD) lead with a floating atrial dipole may permit a single lead (DX) ICD system to detect AHREs. We sought to assess the utility of the DX ICD system for subclinical AF detection in patients, with a prospective multicenter, cohort-controlled trial. METHODS AND RESULTS: One hundred fifty patients without prior history of AF (age 59 ± 13 years; 108 [72%] male) were enrolled into the DX cohort and implanted with a Biotronik DX ICD system at eight centers. Age-, sex-, and left ventricular ejection fraction-matched single- and dual-chamber ICD cohorts were derived from a Cornell database and from the IMPACT trial, respectively. The primary endpoint were AHRE detection at 12 months. During median 12 months follow-up, AHREs were detected in 19 (13%) patients in the DX, 8 (5.3%) in the single-chamber, and 19 (13%) in the dual-chamber cohorts. The rate of AHRE detection was significantly higher in the DX cohort compared to the single-chamber cohort (P = .026), but not significantly different compared to the dual-chamber cohort. There were no inappropriate ICD therapies in the DX cohort. At 12 months, only 3.0% of patients in the DX cohort had sensed atrial amplitudes less than 1.0 mV. CONCLUSION: Use of a DX ICD lead allows subclinical AF detection with a single lead DX system that is superior to that of a conventional single-chamber ICD system.

COVID-19 Can Unveil Brugada: A Rare Case.

Brugada syndrome (BRS) is a channelopathy with three characteristic electrocardiogram patterns and an increased risk of sudden cardiac death (SCD), in the absence of gross structural heart disease. Fever is shown to precipitate ventricular arrhythmias in patients with BRS. Here, we report a rare case of Brugada pattern in a patient with Coronavirus Disease 2019 (COVID-19) without fever. A baseline ECG should be considered for patients with COVID-19, even in the absence of fever. COVID-19 by itself may be a factor that can induce Brugada pattern ECGs.

Left Atrial Appendage Closure: What Do We Know?

Atrial fibrillation (AF) is the most common arrhythmia in the United States and the most common cause of embolic cerebrovascular events, with the majority of these thrombi originating in the left atrial appendage. The left atrial appendage (LAA) has separate developmental, ultrastructural, and physiological characteristics from the left atrium. Although LAA anatomy is highly variable, it can be categorized into 4 types: cactus, cauliflower, chicken wing, and windsock. The cauliflower type is associated with higher stroke risk in patients with nonvalvular AF. Although the cornerstone of therapy to prevent embolic strokes from AF has been anticoagulation with thrombin inhibitors, a large group of patients are unable to tolerate anticoagulation due to bleeding. This has led to the development and advancement of multiple surgical and percutaneous LAA closure devices to prevent embolic cerebrovascular accidents without the need for anticoagulation. In this article, we discuss the outcomes of major studies that utilized surgical LAA occlusion and its effectiveness. Furthermore, we summarize nonsurgical methods of LAA closure and future directions regarding LAA closure.

Prediction of significant conduction disease through noninvasive assessment of cardiac calcification.

AIMS: Cardiac calcification is associated with coronary artery disease, arrhythmias, conduction disease, and adverse cardiac events. Recently, we have described an echocardiographic-based global cardiac calcification scoring system. The objective of this study was to evaluate the severity of cardiac calcification in patients with permanent pacemakers as based on this scoring system. METHODS AND RESULTS: Patients with a pacemaker implanted within the 2-year study period with a previous echocardiogram were identified and underwent blinded global cardiac calcium scoring. These patients were compared to matched control patients without a pacemaker who also underwent calcium scoring. The study group consisted of 49 patients with pacemaker implantation who were compared to 100 matched control patients. The mean calcium score in the pacemaker group was 3.3 ± 2.9 versus 1.8 ± 2.0 (P = 0.006) in the control group. Univariate and multivariate analysis revealed glomerular filtration rate and calcium scoring to be significant predictors of the presence of a pacemaker. CONCLUSION: Echocardiographic-based calcium scoring correlates with the presence of severe conduction disease requiring a pacemaker.

Failure of Complete Endothelialization of a Watchman Device 3 Years Post-Implantation.

We report an unusual case of incomplete endothelialization of the Watchman device >3 years after its implantation. Animal data suggest that device endothelialization occurs ∼45 days post-implantation; however, data on humans are lacking. Guidelines on anticoagulation are based on expectation from animal studies. (Level of Difficulty: Advanced.).

Utility of High-frequency Jet Ventilation in Atrial Fibrillation Ablation.

Atrial fibrillation (AF) is the most common clinically significant arrhythmia that causes major morbidity and mortality. Catheter ablation focusing on pulmonary vein isolation is increasingly used for the treatment of symptomatic AF. Advances in ablation technologies and improved imaging and mapping have enhanced treatment efficiency but only modestly improved the efficacy. Another-but less commonly used-technology that can have a favorable impact involves enhancing the catheter-tissue contact by manipulating respiration to promote improved catheter stability and optimal contact. High-frequency jet ventilation (HFJV) is a mode of ventilation that can reduce respiratory movements to almost apneic conditions. In this review article, we aimed to highlight different studies, review the current literature regarding the utility of HFJV in AF ablation, and discuss the safety and efficacy of this approach relative to that of conventional ventilation.

How transforming growth factor contributes to atrial fibrillation?

Atrial fibrillation (AF) is the most common clinically significant arrhythmia. There are four fundamental pathophysiological mechanisms of AF including: electrical remodeling, structural remodeling, autonomic nervous system changes, and Ca2+ handling abnormalities. The transforming growth factor-ß (TGF-ß) superfamily are cytokines that have the ability to regulate numerous cell functions including proliferation, differentiation, apoptosis, epithelial-mesenchymal transition, and production of extracellular matrix. During the last decade numerous studies have demonstrated that TGF-ß affects the architecture of the heart. TGF-ß1 has been shown to be involved in the development and propagation of atrial fibrillation (AF). Investigators have studied TGF-ß signaling in AF with the aim of discovering potential therapeutic agents. In this review we discuss the role of TGF-ß in atrial fibrillation and specifically its role in atrial structural and electrical remodeling.

Polymorphic Ventricular Tachycardia with a Normal QTc Interval in a Patient with COVID-19 and Fever: Case Report.

Arrhythmias or conduction system disease are not the most common manifestation of COVID-19 infection in patients requiring hospital admission. Torsade de pointes typically occurs in bursts of self-limiting episodes with symptoms of dizziness and syncope. However, it may occasionally progress to ventricular fibrillation and sudden death. In this article, we report a case of COVID-19 patient who developed polymorphic ventricular tachycardia with torsade de pointes morphology with normal QTc interval in the setting of fever. An 81-year-old woman was admitted with symptoms of COVID-19. She was treated with hydroxychloroquine, azithromycin, and doxycycline at an outside facility and finished the treatment 5 days prior to admission to our facility. Her course was complicated by atrial fibrillation with rapid ventricular response requiring cardioversion. Later, she developed two episodes of polymorphic ventricular tachycardia with TdP morphology with normal QTc. There was a correlation with fever triggering the ventricular tachycardia. We advocated aggressive fever control given the QTc was normal and stable. Following fever control, the patient remained stable and had no abnormal rhythm. COVID-19 patients are prone to different arrhythmias including life-threatening ventricular arrhythmias with normal left ventricular systolic function and normal QTc, and they should be monitored for fever and electrolyte abnormality during their hospital stay.

Atrioventricular and Sinus Node Dysfunction in Stable COVID-19 Patients.

There are now well-documented cardiac complications of COVID-19 infection which include myocarditis, heart failure, and acute coronary syndrome resulting from coronary artery thrombosis or SARS-CoV-2-related plaque ruptures. There is growing evidence showing that arrhythmias are also one of the major complications. We report two patients with no known history of cardiac conduction disease who presented with COVID-19 symptoms, positive SARS-CoV-2 infection, and developed cardiac conduction abnormalities. Cardiac conduction system disease involving the sino-atrial (SA) node and atrioventricular (AV) node could be a manifestation of SARS-CoV-2 infection.

Site-specific atherogenic gene expression correlates with subsequent variable lesion development in coronary and peripheral vasculature.

OBJECTIVE: The relationship between specific gene regulation and subsequent development and progression of atherosclerosis is incompletely understood. We hypothesized that genes in the vasculature related to cholesterol metabolism, inflammation, and insulin signaling pathways are differentially regulated in a site-specific and time-dependent manner. METHODS AND RESULTS: Expression of 59 genes obtained from coronary, carotid, and thoracic aortic arteries were characterized from diabetic (DM)/hypercholesterolemic (HC) swine (n=52) 1, 3, and 6 months after induction. Lesion development in the 3 arterial beds was quantified and characterized at 1, 3, 6, and 9 months. Progressive lesion development was observed in the coronary>thoracic aorta>>carotid arteries. Genes involved in cholesterol metabolism and insulin pathways were upregulated in coronaries>thoracic aortae>carotids. Inflammatory genes were more markedly upregulated in coronary arteries than the other 2 arteries. Genes implicated in plaque instability (eg, matrix metalloproteinase-9, CCL2 and Lp-PLA(2) mRNAs) were only upregulated at 6 months in coronary arteries. CONCLUSIONS: Variable gene expression, both in regard to the arterial bed and duration of disease, was associated with variable plaque development and progression. These findings may provide further insight into the atherosclerotic process and development of potential therapeutic targets.

Utility of Contact Impedance Mapping in Differentiating the Mechanism of Focal Atrial Tachycardia.

Contact impedance mapping can differentiate focal atrial tachyarrhythmias from macroreentry (atrial flutter) and localized reentry (atrioventricular nodal reentry tachycardia) by detecting different patterns of regional unipolar tissue impedance distribution. Specifically, focal atrial tachycardia (AT) is characterized by the finding of a contiguous low-impedance area (CLIA) adjacent to the site of origin, surrounded by normal tissue impedance levels. However, it remains unclear whether or not this finding could distinguish different mechanisms of focal AT. In the present study, we sought to determine whether impedance and voltage maps in patients with microreentrant AT differ from those created due to triggered activity. Consecutive patients undergoing electrophysiologic study and the ablation of AT were included. All patients underwent mapping and ablation procedures in a standard manner. Contact impedance and voltage maps were collected in the background and analyzed offline for comparison. A total of 50 patients with 75 focal ATs were studied and ablated, and the mechanism of AT (ie, triggered activity versus microreentry) was determined. The 41 ATs attributed to triggered activity in 30 patients all demonstrated a CLIA containing or adjacent to the successful ablation site, while the 34 ATs in the 20 patients attributed to microreentry demonstrated uniform impedance. In contrast, microreentrant AT patients were more likely to have scar located adjacent to the site of origin (88.9% versus 18.2%). Three-dimensional mapping employing both contact impedance mapping and voltage mapping can reliably identify the mechanism of focal AT.

CT based 3D printing is superior to transesophageal echocardiography for pre-procedure planning in left atrial appendage device closure.

Accurate assessment of the left atrial appendage (LAA) is important for pre-procedure planning when utilizing device closure for stroke reduction. Sizing is traditionally done with transesophageal echocardiography (TEE) but this is not always precise. Three-dimensional (3D) printing of the LAA may be more accurate. 24 patients underwent Watchman device (WD) implantation (71 ± 11 years, 42% female). All had complete 2-dimensional TEE. Fourteen also had cardiac computed tomography (CCT) with 3D printing to produce a latex model of the LAA for pre-procedure planning. Device implantation was unsuccessful in 2 cases (one with and one without a 3D model). The model correlated perfectly with implanted device size (R2 = 1; p < 0.001), while TEE-predicted size showed inferior correlation (R2 = 0.34; 95% CI 0.23-0.98, p = 0.03). Fisher's exact test showed the model better predicted final WD size than TEE (100 vs. 60%, p = 0.02). Use of the model was associated with reduced procedure time (70 ± 20 vs. 107 ± 53 min, p = 0.03), anesthesia time (134 ± 31 vs. 182 ± 61 min, p = 0.03), and fluoroscopy time (11 ± 4 vs. 20 ± 13 min, p = 0.02). Absence of peri-device leak was also more likely when the model was used (92 vs. 56%, p = 0.04). There were trends towards reduced trans-septal puncture to catheter removal time (50 ± 20 vs. 73 ± 36 min, p = 0.07), number of device deployments (1.3 ± 0.5 vs. 2.0 ± 1.2, p = 0.08), and number of devices used (1.3 ± 0.5 vs. 1.9 ± 0.9, p = 0.07). Patient specific models of the LAA improve precision in closure device sizing. Use of the printed model allowed rapid and intuitive location of the best landing zone for the device.

Incidence and predictors of very late recurrence of atrial fibrillation after ablation.

INTRODUCTION: Radiofrequency catheter ablation can effectively treat patients with refractory atrial fibrillation (AF). Very late AF recurrence (> or = 12 months post-ablation) is uncommon and may represent a unique patient cohort. METHODS AND RESULTS: A nested case-control study was performed in the cohort who underwent AF ablation at the University of Pennsylvania to characterize patients who develop very late AF recurrence after ablation. The procedure consisted of isolation of pulmonary veins (PVs) demonstrating triggers and elimination of non-PV triggers initiating AF. Twenty-seven (7.9%) patients with very late recurrence were compared to 219 patients without recurrence and > or = 12 months of follow-up. The mean age was 54.6 +/- 11.3 years and 79% were men. Very late recurrence patients more likely weighed >200 lbs (70% vs 55%, P = 0.01); during initial ablation had fewer PVs isolated (2.8 +/- 1.1 vs 3.3 +/- 1.0, P = 0.03); and were less likely to have right inferior PV isolation (37% vs 61%, P = 0.02), less likely to have isolation of all PVs (30% vs 56%, P = 0.01), and more likely to have non-PV triggers (30% vs 11% OR 3.4(95% CI, 1.3-8.7), P = 0.01). PV reconnectivity and new triggers were found in the majority of patients with very late recurrence of AF who underwent repeat ablation. CONCLUSION: Very late recurrence of AF more likely occurred in patients >200 lbs who demonstrated non-PV triggers and did not undergo right inferior PV isolation. The majority of patients undergoing repeat ablation for very late recurrence demonstrated PV reconnectivity and new non-PV and PV triggers not observed during the initial ablation.

Elevated defibrillation thresholds in patients undergoing biventricular defibrillator implantation: incidence and predictors.

BACKGROUND: The biventricular implantable cardioverter-defibrillator (ICD) is an important therapy for select patients with severe heart failure. Given reported risk factors for elevated defibrillation thresholds (DFTs), patients undergoing biventricular ICD placement would be suspected of having a higher incidence of elevated DFT. OBJECTIVES: The purpose of this study was to examine the clinical predictors and mortality risk of elevated DFTs in patients receiving a biventricular ICD. METHODS: Characteristics of patients undergoing biventricular ICD placement with an elevated DFT were compared to those without an elevated DFT. RESULTS: An elevated DFT was found in 14 (12%) of 121 patients. Mean QRS duration was 210 +/- 50 ms in the elevated DFT group and 171 +/- 36 ms in the normal DFT group (P = .01). Patients with a QRS duration >or=200 ms were more likely to have an elevated DFT than those with a duration <200 ms (odds ratio 13.4, 95% confidence interval 3.1-66.7, P <.01). No other clinical characteristics were associated with an elevated DFT. More than 90% of patients with an elevated DFT achieved an adequate safety margin through system modification or manipulation of their drug regimen. An elevated DFT did not have an impact on 2-year mortality. CONCLUSION: Patients with a biventricular ICD had a 12% incidence of elevated DFT in our sequential patient cohort. QRS duration prior to biventricular ICD placement is the most powerful predictor of patients at risk for an elevated DFT. An elevated DFT does not have an impact on mortality, perhaps because of successful implementation of system modifications to ensure an adequate defibrillation safety margin.

Relative contributions of intimal hyperplasia and vascular remodeling in early cardiac transplant-mediated coronary artery disease.

The relative contribution of intimal hyperplasia and vascular remodeling in early transplant coronary artery disease (TxCAD) is unknown. This study was designed to determine the contributions of vascular remodeling and intimal hyperplasia in the initial year after transplantation by intravascular ultrasound (IVUS). Twenty-five patients underwent baseline (<6 weeks after transplant) and 1-year angiography and IVUS to evaluate total vessel, luminal, and intimal + medial areas in >or=3 segments of the coronary artery. Nine patients had donor atherosclerotic disease on baseline study (23% of segments), and at 1-year, 21 patients (84%) had intimal hyperplasia (70% of segments). Fourteen patients had positive remodeling in all arterial segments, whereas the remaining 11 had positive and negative remodeling in the same vessel. Mean plaque area and total vessel area increased significantly (p = 0.0001) in proximal, mid, and distal segments, whereas total vessel area was most pronounced in distal segments. Luminal area did not change over time. Of the 87 segments evaluated, 68 (78%) had an increase in total vessel area, 57 (66%) had intimal growth, and 54 (62%) had an increase in luminal area. Although changes in total vessel and luminal area were closely correlated, a decrease in luminal area was associated with positive and negative remodeling. In conclusion, luminal area is generally maintained during the initial transplant year despite significant intimal hyperplasia due to positive remodeling. Reduction in the luminal area results from either inadequate positive remodeling or negative remodeling without intimal growth and often occurs in the same artery.