Prevalence and predictors of difficult vascular anatomy in forearm artery access for coronary angiography and PCI.

Transradial access has established as preferred access for cardiac catheterization. Difficult vascular anatomy (DVA) is a noticeable threat to procedural success. We retrospectively analyzed 1397 consecutive cardiac catheterizations to estimate prevalence and identify predictors of DVA. In the subclavian-innominate-aortic-region (SIAR), DVA was causing failure in 2.4% during right-sided vs. 0.7% in left-sided forearm-artery-access (FAA) attempts (χ2 = 5.1, p = 0.023). Independent predictors were advanced age [odds ratio (OR) 1.44 per 10-year increase, 95% confidence interval (CI) 1.15 to 1.80, p = 0.001] and right FAA (OR 2.52, 95% CI 1.72 to 3.69, p < 0.001). In the radial-ulnar-brachial region (RUBR), DVA was causing failure in 2.5% during right-sided vs. 1.7% in left-sided FAA (χ2 = 0.77, p = 0.38). Independent predictors were age (OR 1.28 per 10-year increase, 95% CI 1.01 to 1.61, p = 0.04), lower height (OR 1.56 per 10-cm decrease, 95% CI 1.13 to 2.15, p = 0.008) and left FAA (OR 2.15, 95% CI 1.45 to 3.18, p < 0.001). Bilateral DVA was causing procedural failure in 0.9% of patients. The prevalence of bilateral DVA was rare. Predictors in SIAR were right FAA and advanced age and in RUBR, left FAA, advanced age and lower height. Gender, arterial hypertension, body mass, STEMI and smoking were not associated with DVA.

Standardized Forearm Angiography Increases Procedural Success Rates of Coronary Angiography and PCI: A Retrospective Analysis of an all-Comers Patient Cohort in a Real-Life Scenario.

Background: There is a consensus, that Transradial-Access (TRA) for coronary procedures should be preferred over Transfemoral-Access (TFA). Previously, Forearm-Artery-Angiography (FA) was mainly performed when difficulties during the advancement of the guidewire/-catheter were encountered. We explored the implication of a Standardized Forearm-Angiography (SFA) on procedural success rates of TRA under real-world conditions. Methods: In a single-center study, an all-comers-cohort of 1191 consecutive cases during 1/2020-12/2020 were assessed retrospectively. Primary TFA rates, crossover to TFA, reasons for Forearm-Artery-Access (FAA) failure, the prevalence of kinking at the level of the forearm and the occurrence of vascular complications were analyzed. Major forearm side branches including the common interosseus artery were assessed via SFA. Results: In 1191 consecutive procedures, primary FAA access was attempted in 97.9% of cases. Crossover to TFA after a primary or secondary FAA attempt was necessary in 2.8%. Severe kinking was the most frequent cause of FAA failure and occurred in 3.0% of attempts. A second or third FAA attempt to avoid TFA was successful in 81%. Severe kinking at the level of the forearm was reported in 1.8% of procedures. Conclusion: This is the first study to provide detailed success rates of a primary FAA strategy combined with a Standardized-Forearm-Angiography (SFA) in an all-comers-cohort. While severe kinking proved to be a rare but relevant challenge for FAA success, the prevalence of arterial spasm was marginal. Multiple attempts of FAA to avoid TFA might be safe possibly due to collateral blood supply by the common interosseus artery.

Correlation of magnetic resonance imaging and post-ablation endoscopy to detect oesophageal thermal injury in patients after atrial fibrillation ablation: MRI-EDEL-study.

AIMS: To correlate oesophageal magnetic resonance imaging (MRI) abnormalities with ablation-induced oesophageal injury detected in endoscopy. METHODS AND RESULTS: Ablation-naïve patients with atrial fibrillation (AF), who underwent ablation using a contact force sensing irrigated radiofrequency ablation catheter, received a cardiac MRI on the day of ablation, and post-ablation oesophageal endoscopy (OE) 1 day after ablation. Two MRI expert readers recorded presence of abnormal oesophageal tissue signal intensities, defined as increased oesophageal signal in T2-fat-saturated (T2fs), short-tau inversion-recovery (STIR), or late gadolinium enhancement (LGE) sequences. Oesophageal endoscopy was performed by experienced operators. Finally, we correlated the presence of any affection with endoscopically detected oesophageal thermal lesions (EDEL). Among 50 consecutive patients (age 67 ± 7 years, 60% male), who received post-ablation MRI and OE, complete MRI data were available in 44 of 50 (88%) patients. In OE, 7 of 50 (14%) presented with EDEL (Category 1 lesion: erosion n = 3, Category 2 lesion: ulcer n = 4). Among those with EDEL, 6 of 7 (86%) patients presented with increased signal intensities in all three MRI sequences, while only 2 of 37 (5%) showed hyperintensities in all three MRI sequences and negative endoscopy. Correspondingly, sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for MRI (increased signal in T2fs, STIR, and LGE) were 86%, 95%, 75%, and 97%, respectively. CONCLUSION: Increased signal intensity in T2fs, STIR, and LGE represents independent markers of EDEL. In particular, the combination of all three has the highest diagnostic value. Hence, MRI may represent an accurate, non-invasive method to exclude acute oesophageal injury after AF ablation (NPV: 97%).

Left atrial functional and structural changes associated with ablation of atrial fibrillation - Cardiac magnetic resonance study.

INTRODUCTION: Left atrial (LA) volumes are related to success of atrial fibrillation (AF) ablation, but the relation to other functional and structural parameters is less well understood. Our goal was to detect potential functional and structural predictors of arrhythmia recurrence after ablation using cardiac magnetic resonance imaging (CMRi) and to non-invasively assess the relation between LA functional and structural remodeling pre- and post-ablation. METHODS: A total of 55 patients (38 male, age 67 ± 10 years) underwent CMRi prior to and then within 24-h and 3-months after ablation. LA volumes (LAV) and function (as assessed by ejection fraction and peak longitudinal atrial strain (PLAS)) were measured by feature-tracking CMRi, and LA fibrosis/scarring was quantified using late­gadolinium enhancement (LGE) imaging. RESULTS: Atrial function was lower acutely in patients with recurrence versus those with non-recurrence: [R vs NR: EFTotal 27.8 ± 10.3% vs 38.1 ± 11% p = 0.002; EFActive 10.5 ± 8% vs 19.1 ± 12% p = 0.007; EFPassive 19.4 ± 8 vs 25.8 ± 10 p = 0.021; PLAS 13 ± 5.9% vs 20.2 ± 7% p = 0.004]. With univariate analysis, baseline minimum volume (MinLAV, MinLAVi), several baseline functional parameters (EFTotal, EFPassive, EFActive, PLAS), and LA-LGE were predictors of recurrence [all p < 0.05]. Acute function (EFTotal, EFPassive, EFActive, PLAS) also predicted recurrence (p < 0.01). Lower pre-ablation EFTotal, EFPassive, and PLAS correlated with higher amount of pre-ablation LA-LGE (p < 0.05). In a multivariate model including MinLAV, EFActive and LA-LGE (all at baseline), LA-LGE was the only independent predictor of recurrence (p = 0.0322). CONCLUSION: Pre-ablation function inversely correlated with LA-LGE and was related to success of AF ablation. Multi-parametric and longitudinal assessment of LA function and structure could be helpful in selection of optimal treatment strategies for AF patients by predicting outcomes.

Late Gadolinium Enhancement Magnetic Resonance Imaging Guided Treatment of Post-Atrial Fibrillation Ablation Recurrent Arrhythmia.

BACKGROUND: Macroreentrant atrial tachycardia (AT) accounts for 40% to 60% of recurrent atrial arrhythmias after atrial fibrillation (AF) ablation. To describe late gadolinium enhancement magnetic resonance imaging (LGE-MRI)-detected scar-based dechanneling as new ablation strategy to treat ATs after AF ablation. METHODS: Data from 102 patients who underwent initial AF ablation and repeat ablation for recurrent atrial arrhythmia within 1-year follow-up were analyzed. All patients underwent LGE-MRI before initial and repeat ablation. Depending on the recurrent rhythm, patients with AF and AT recurrence were assigned to group 1 or 2, respectively. Group 1 underwent fibrosis homogenization as second procedure. Group 2 underwent LGE-MRI-detected scar-based dechanneling. Both groups underwent reisolation of pulmonary veins if necessary. RESULTS: Forty-six patients (45%) presented with AF, and 56 patients (55%) presented with AT recurrence during follow-up after initial ablation. In the first 25 patients from group 2, the AT was electroanatomically mapped, and a critical isthmus was defined. It was found that those isthmi were located in the regions with nontransmural scarring detected by LGE-MRI. In the last 31 patients from group 2, an empirical LGE-MRI-based dechanneling was performed solely based on the LGE-MRI results. During 1-year follow-up after second ablation, 67% patients in group 1 and 64% patients in group 2 were free from recurrence (log-rank, P=1.000). In group 2, 64% in the electroanatomically guided and 65% in the LGE-MRI dechanneling group were free from recurrence (log-rank, P=0.900). CONCLUSIONS: Anatomic targeting of LGE-MRI-detected gaps and superficial atrial scar is feasible and effective to treat recurrent arrhythmias post-AF ablation. Homogenization of existing scar is the appropriate treatment for recurrent AF, whereas dechanneling of existing isthmi seems the right approach for patients recurring with AT.

High-Resolution Infrared Thermal Imaging of the Esophagus During Atrial Fibrillation Ablation as a Predictor of Endoscopically Detected Thermal Lesions: Results From the HEAT-AF Study.

BACKGROUND: Endoscopically detected thermal esophageal lesions (EDEL) after ablation of atrial fibrillation may be precursors of atrioesophageal fistula and esophageal luminal temperature monitoring has previously failed to decrease thermal damage. METHODS: Sixty-three patients undergoing their first pulmonary vein isolation using radiofrequency point-by-point catheter ablation were prospectively included in the HEAT-AF study (High-Resolution Esophageal Assessment of Esophageal Temperature During Atrial Fibrillation Ablation) and esophageal temperatures were continuously monitored using a novel infrared thermography system (IRTS). Peak esophageal temperature (Tpeak) was correlated to postablation endoscopy results characterizing patients as EDEL positive or negative. RESULTS: Twelve patients had EDEL (19%). Comparing EDEL positive to negative patients, Tpeak was significantly higher (56.3±4.6°C versus 45.7±5.5°C, P<0.0001). Logistic regression analysis demonstrated Tpeak was a statistically significant predictor ( P=0.0008) of EDEL and yielded an odds ratio of 1.52; 95% CI, (1.24-2.05). Receiver operator curve analysis demonstrated Tpeak as a highly accurate binary classifier with an area under the curve of 93%. CONCLUSIONS: For the first time esophageal temperature monitoring using a high resolution, high-fidelity IRTS allowed accurate prediction of postablation EDEL suggesting that Tpeak alone is an excellent binary classifier of patients at risk of EDEL. The logistic regression model and associated receiver operator curve will aid in the selection of optimal temperature thresholds in future prospective studies.

Progression From Esophageal Thermal Asymptomatic Lesion to Perforation Complicating Atrial Fibrillation Ablation: A Single-Center Registry.

BACKGROUND: Up to 40% of patients demonstrate endoscopically detected asymptomatic esophageal lesions (EDEL) after atrial fibrillation ablation. METHODS AND RESULTS: Patients undergoing first atrial fibrillation ablation and postinterventional esophageal endoscopy were included in the study. Occurrence of esophageal perforating complications during follow-up was related to documented EDEL (category 1: erythema/erosion; category 2: ulcer). In total, 1802 patients underwent first atrial fibrillation ablation procedure between January 2013 and August 2016 at our institution. Out of this group, 832 patients (506 male patients, 61%; 64.0±10.0 years) with symptomatic paroxysmal (n=345; 42%) or persistent atrial fibrillation underwent postprocedural esophageal endoscopy. Patients were ablated using single-tip ablation with conventional or surround flow irrigation and circular ablation catheters with open irrigation (nMARQ). In 295 of 832 patients (35%), a temperature probe was used. EDEL occurred in 150 patients (18%; n=98 category 1 EDEL, n=52 category 2 EDEL). In 5 of 832 patients (0.6%), an esophageal perforation (n=3) or an esophagopericardial or atrioesophageal fistula (n=2) occurred 15 to 28 days (19±6 days) after ablation. Two patients (1 atrioesophageal fistula and 1 esophagopericardial fistula) died. Esophageal perforation occurred only in patients with category 2 lesions (absolute risk, 9.6%). In a logistic regression analysis, ulcers were identified to be a significant predictor for esophageal perforating complications. CONCLUSIONS: Postablation endoscopy seems to identify patients at high risk of esophageal perforating complications only occurring in patients with category 2 EDEL. One out of 10 postablation esophageal ulcers progressed to perforation, and no patient without esophageal thermal ulcers showed the occurrence of perforating esophageal complications.

Repetitive atrial activation during ongoing atrial fibrillation-comparison using different mapping algorithms: preliminary findings.

PURPOSE: Targeting repetitive sources identified during atrial fibrillation (focal impulse and rotor modulation, FIRM) has been used as an ablation strategy using specific mapping tools. Aim of this study was to evaluate FIRM mapped rotors with a new multipolar mapping algorithm. METHODS: Patients with persistent atrial fibrillation undergoing FIRM ablation were included. Mapping of left atrial rotors was performed with a 64-pole basket catheter in conjunction with a specialized phase mapping algorithm. Subsequently, raw signals were analyzed by a novel mapping system (CARTOFINDER™). Comparison of FIRM identified sources with areas of repetitive activation analyzed by CARTOFINDER™ was performed. RESULTS: Nine patients were included (5 redo procedures; male n = 6; 66.5 ± 8.6 years) and 28 left atrial rotors were compared with the findings of the novel mapping system. CARTOFINDER™ identified repetitive activation patterns in 6 mapping sequences at remote sites (2 rotational patterns, 4 linear activation patterns). CONCLUSIONS: In this comparative preliminary study, two different mapping technologies to detect repetitive atrial activation during ongoing AF were used. Whereas rotational activation was documented using FIRM mapping no corresponding repetitive activation patterns near sites of FIRM-mapped rotor cores were identified using the novel mapping technology even though using the same electrogram characteristics and mapping basket position.

[Catheter ablation of ventricular extrasystoles and ventricular tachycardia in the elderly]. / Katheterablation ventrikulärer Extrasystolen und Kammertachykardien im hohen Alter.

BACKGROUND: The prevalence of structural heart disease increases with higher age, and thereby the basis for ventricular arrhythmias is created. Catheter ablation has been shown to be an effective therapy option that is very safe and achieves good long-term results in patients with recurrent ventricular tachycardia (VT). Data regarding ablation in patients older than 75 years is sparse, although this patient group was included as a minority in most published VT ablation studies. Data from younger patient collectives may not be transferable to older patient cohorts due to differences in patient comorbidities and baseline characteristics. METHODS: Studies with patient collectives ≥75 years or even ≥80 years show comparable efficacy of catheter ablation for VT; however, the complication rate is higher, mainly due to groin complications, increases. Catheter ablation of ischemic VT appears effective and safe even in ≥75 year olds; however, extensive data for other structural heart diseases are lacking. Epicardial procedures are also possible and safe in older patients (≥80 years). Due to the significant challenges of VT ablation in older patients, including the consideration of complex comorbidities, these should be performed in specialized centers with high expertise. CONCLUSION: The aim of catheter ablation in older patients is, above all, to improve quality of life and morbidity. Long-term survival is significantly lower due to the "near end of life" situation than in younger patients. Careful consideration of alternative therapy options, chances for success of the catheter ablation, and their risks, taking into account specific patient conditions and symptoms, is crucial in these patients.

Impact of surround flow catheter tip irrigation in contact force ablation on the incidence of asymptomatic oesophageal lesions after atrial fibrillation ablation: a prospective comparative study.

AIMS: Aim of this study was to evaluate the impact of a recently introduced contact force ablation catheter with modified irrigation technology compared with a conventionally irrigated ablation catheter on the incidence of endoscopically detected oesophageal lesions (EDEL). METHODS AND RESULTS: Patients with symptomatic, drug-refractory paroxysmal or persistent atrial fibrillation (AF) who underwent left atrial radiofrequency (RF) catheter ablation were prospectively enrolled. Patients were ablated using a single-tip RF contact force ablation catheter with conventional irrigation (Group 1; n = 50) or with a recently introduced intensified 'surround flow' irrigation technology (Group 2; n = 50). Assessment of EDEL was performed by oesophagogastroduodenoscopy in all patients after ablation. A total of 100 patients (mean age 63.6 ± 12.1 years; men 58%) with paroxysmal (n = 41; 41%) or persistent AF were included. Groups 1 and 2 patients were comparable in regard to baseline characteristics and procedural parameters, especially ablation time at posterior left atrial wall. Overall, 13 patients (13%) developed EDEL after AF ablation (8 oesophageal ulcerations, 5 erythema). The incidence of EDEL including oesophageal ulcerations was higher in Group 2 compared with Group 1 patients without statistical significance (18 vs. 8%, P = 0.23). One pericardial tamponade and one access site bleeding occurred in Group 2. No further adverse events were reported in both groups. CONCLUSION: According to these preliminary results, the use of an improved ablation catheter irrigation technology (surround flow) in conjunction with contact force measurement was associated with a higher but not statistically significant probability of oesophageal thermal lesions. Further studies including larger patient cohorts are needed.

Impact of periprocedural anticoagulation strategy on the incidence of new-onset silent cerebral events after radiofrequency catheter ablation of atrial fibrillation.

BACKGROUND: Silent cerebral events (SCEs) have been observed on diffusion-weighted cerebral magnetic resonance imaging (MRI) in a substantial number of asymptomatic patients after atrial fibrillation (AF) ablation procedures. The purpose of this study was to investigate if periprocedural oral anticoagulation (OAC) management affects the incidence of new-onset SCE after radiofrequency catheter ablation (RFCA) of AF. METHODS AND RESULTS: One hundred ninety-two consecutive patients (64 ± 10.1 years, 38.5 % women) with symptomatic paroxysmal (n = 80, 41.7 %) or persistent AF undergoing RFCA of AF were prospectively enrolled. Periprocedural anticoagulation strategies were defined as uninterrupted use of novel oral anticoagulants (NOACs) (group I, n = 64), interrupted use of NOACs (group II, n = 42), continuation of vitamin K antagonist (VKA) with an international normalized ratio (INR) between 2.0 and 3.0 (group III, n = 43), and VKA discontinuation bridged with low molecular weight heparin (group IV, n = 43). Cerebral MRI was performed 1 to 2 days after RFCA for detection of new SCE. Overall, new SCEs were detected in 41 patients (21.4 %) after AF ablation. New SCEs were detected in 12.5 % in group I, 35.7 % in group II, 18.6 % in group III, and 23.3 % in group IV (p < 0.05). Multivariable logistic regression analysis revealed persistent AF and discontinuation of periprocedural OAC (group II and IV) to be independent predictors for the development of SCE. No relevant complications were identified. CONCLUSIONS: Periprocedural continuation of NOAC as well as continuation of VKA seems to be safe and significantly reduce the occurrence of SCE after AF ablation.

[Differential diagnosis of tachycardia with a broad QRS-complex]. / Differenzialdiagnostik der Breitkomplex-Tachykardie.

INTRODUCTION: The electrocardiographic (ECG) differential diagnosis of tachycardia with a broad QRS complex (BCT) represents a challenge for physicians but is important for adequate treatment and risk evaluation. Differentiated algorithms have been established and can increase the specificity of the diagnosis in individual patients but are often hampered by complexity and yield a pragmatic ECG approach. METHODS AND RESULTS: Irregular BCTs (irregular R-R distances) despite the patient being hemodynamically stable are almost always due to atrial fibrillation with bundle branch block (pre-existing or functional) or conduction via accessory pathways. In contrast, sustained polymorphic ventricular tachycardia (VT) is always associated with hemodynamic collapse. In regular BCT the following mechanisms must be differentiated: (1) VT, (2) supraventricular tachycardia (SVT) with bundle branch block or (3) SVT with pre-excitation via accessory pathways, e.g. Wolff-Parkinson-White (WPW) syndrome. The presence of an underlying structural heart disease, specifically a history of myocardial infarction is suggestive of VT. For a differentiated analysis in hemodynamically stable patients a 12-lead ECG is essential. CONCLUSION: Identification of signs of atrioventricular (AV) dissociation or a negative precordial concordance of QRS are indicative of VT. In V1 positive BCTs a positive precordial concordance, QRS width > 140 ms, superiorly directed QRS axis, monophasic or biphasic QRS complexes in V1 and deep S wave in V6 are indications of a VT. In V1 negative BCTs, QRS width > 160 ms, right-sided QRS axis, broad R peak (> 40 ms) in V1/V2, slurred S downstroke in V1/V2 and any Q peak in V6 are all indications of VT as the mechanism.

Effect of Different Ablation Settings on Acute Complications Using the Novel Irrigated Multipolar Radiofrequency Ablation Catheter (nMARQ).

BACKGROUND: Single-shot ablation devices for pulmonary vein isolation (PVI) in patients with symptomatic atrial fibrillation (AF) have been increasingly used in clinical practice. OBJECTIVE: A novel mapping-system integrated irrigated multipolar circular ablation catheter (nMARQ) has been introduced for PVI but data on larger patient cohorts on acute safety and efficacy are lacking. METHODS: A total of 145 consecutive patients undergoing AF ablation treated with the nMARQ underwent endoscopic evaluation of esophageal thermal damage (EDEL) and brain MRI for detection of silent cerebral events (SCE). During the course of our experience different modifications of the ablation strategy, including energy delivery at the left atrial posterior wall, were evaluated. RESULTS: Effective PVI was achieved in 99% of all PVs during a mean procedure-duration of 115 (±36) minutes and ablation-duration of 18 (±8) minutes. Acute major complications occurred in 3 patients (2.1%) and asymptomatic complications like SCE in 26% and EDEL in 21%. There was a significant reduction in EDEL when not using a thermal esophageal probe (0% vs. 28%, P < 0.0001). Ablation under oral anticoagulation led to lower SCE incidences compared to interrupted anticoagulation regimen (15% vs. 31%, P = 0.7). Out of 65 patients with completed 12-month follow-up, 43 (66%) were in stable sinus rhythm. CONCLUSIONS: PVI using the nMARQ is safe and effective in patients with symptomatic AF. Not using an esophageal temperature probe during ablation has relevantly reduced the incidence of EDEL. Ablations under continued oral anticoagulation have reduced incidence of SCE. Further studies on long-term efficacy are needed.

Higher incidence of esophageal lesions after ablation of atrial fibrillation related to the use of esophageal temperature probes.

BACKGROUND: Endoscopically detected esophageal lesions (EDELs) have been identified in apparently asymptomatic patients after catheter ablation of atrial fibrillation (AF). The use of esophageal probes to monitor luminal esophageal temperature (LET) during catheter ablation to protect esophageal damage is currently controversial. OBJECTIVE: The purpose of this study was to investigate the impact of the use of esophageal temperature probes during AF catheter ablation on the incidence of EDELs. METHODS: Eighty consecutive patients (mean age 63.8 ± 11.36 years; 68.8% men) with symptomatic, drug-refractory paroxysmal (n = 52, 65%) or persistent AF who underwent left atrial radiofrequency catheter ablation were prospectively enrolled. Posterior wall ablation was power limited (≤25 W). In the first 40 patients, LET was monitored continuously (group A), whereas no esophageal temperature probe was used in group B (n = 40 patients). Assessment of EDEL was performed by endoscopy within 2 days after radiofrequency catheter ablation. RESULTS: Overall, 13 patients (16%) developed EDELs after AF ablation. The incidence of EDELs was significantly higher in group A than group B (30% vs 2.5%, P < .01). Within group A, patients who developed EDEL had higher maximal LET during AF ablation than patients without EDEL (40.97 ± 0.92°C vs 40.14 ± 1.1°C, P = .02). Multivariable logistic regression analysis revealed the use of an esophageal temperature probe as the only independent predictor for the development of EDEL (odds ratio 16.7, P < .01). CONCLUSION: The use of esophageal temperature probes in the setting of AF catheter ablation per se appears to be a risk factor for the development of EDEL.

Hydrogen sulfide-releasing aspirin derivative ACS14 exerts strong antithrombotic effects in vitro and in vivo.

OBJECTIVE: Hydrogen sulfide (H(2)S)-releasing NSAIDs exert potent anti-inflammatory effects beyond classical cyclooxygenase inhibition. Here, we compared the platelet inhibitory effects of the H(2)S-releasing aspirin derivative ACS14 with its mother compound aspirin to analyze additional effects on platelets. METHODS AND RESULTS: In platelets of mice fed with ACS14 for 6 days (50 mg/kg per day), not only arachidonic acid-induced platelet aggregation but also ADP-dependent aggregation was decreased, an effect that was not observed with an equimolar dose of aspirin (23 mg/kg per day). ACS14 led to a significantly longer arterial occlusion time after light-dye-induced endothelial injury as well as decreased thrombus formation after ferric chloride-induced injury in the carotid artery. Bleeding time was not prolonged compared with animals treated with equimolar doses of aspirin. In vitro, in human whole blood, ACS14 (25-500 µmol/L) inhibited arachidonic acid-induced platelet aggregation, but compared with aspirin additionally reduced thrombin receptor-activating peptide-, ADP-, and collagen-dependent aggregation. In washed human platelets, ACS14 (500 µmol/L) attenuated αIIbß3 integrin activation and fibrinogen binding and increased intracellular cAMP levels and cAMP-dependent vasodilator-stimulated phosphoprotein (VASP) phosphorylation. CONCLUSIONS: The H(2)S-releasing aspirin derivative ACS14 exerts strong antiaggregatory effects by impairing the activation of the fibrinogen receptor by mechanisms involving increased intracellular cyclic nucleotides. These additional antithrombotic properties result in a more efficient inhibition of thrombus formation in vivo as achieved with aspirin alone.

Site directed vascular gene delivery in vivo by ultrasonic destruction of magnetic nanoparticle coated microbubbles.

Site specific vascular gene delivery for therapeutic implications is favorable because of reduction of possible side effects. Yet this technology faces numerous hurdles that result in low transfection rates because of suboptimal delivery. Combining ultrasonic microbubble technology with magnetic nanoparticle enhanced gene transfer could make it possible to use the systemic vasculature as the route of application and to magnetically trap these compounds at the target of interest. In this study we show that magnetic nanoparticle-coated microbubbles bind plasmid DNA and successfully deliver it to endothelial cells in vitro and more importantly transport their cargo through the vascular system and specifically deliver it to the vascular wall in vivo at sites where microbubbles are retained by magnetic force and burst by local ultrasound application. This resulted in a significant enhancement in site specific gene delivery compared with the conventional microbubble technique. Thus, this technology may have promising therapeutic potential. FROM THE CLINICAL EDITOR: This work focuses on combining ultrasonic microbubble technology with magnetic nanoparticle enhanced gene transfer to enable targeted gene delivery via the systemic vasculature and magnetic trapping of these compounds at the target of interest.