Usefulness of intracardiac echocardiography with a mechanical probe for catheter-based interventions: a 10-year prospective registry.

BACKGROUND: The clinical outcome benefit of intracardiac echocardiography (ICE) with a mechanical probe during congenital heart disease interventions has not been fully investigated. We reported the long-term results of a prospective registry of interatrial shunt closure guided by mechanical ICE. METHODS: We enrolled 537 patients (mean age 48 ± 19.0 years, 378 females) submitted to ICE-aided procedures in a prospective registry over a 10-year period (September 2003-September 2013). All patients underwent transesophageal echocardiography (TEE) before the planned procedure. We evaluated (1) structure identification capability, (2) fossa ovale and interatrial septum component measurement, (3) procedure monitoring capability, (4) procedural and fluoroscopy times, and radiograph dose, (5) probe-related complications. RESULTS: ICE was successfully performed and was able to correctly identify the structures previously assessed by TEE in all patients. In 24 patients (4.5%), ICE allowed better anatomy definition than TEE. In 35 other patients (6.5%), ICE identified structures not observed by TEE, which led to change indications to interventions or the operative technique to be used. In 131 patients (24.4%), ICE evaluation led to change the planned device to be implanted. There was only one probe-related complication (0.2%). CONCLUSIONS: Mechanical ICE may offer a valid alternative to conventional TEE in guiding congenital heart disease interventional procedures.

Transradial Szabo technique for intervention of ostial lesions.

OBJECTIVES: The aim of our study is to assess the feasibility and safety of transradial intervention (TRI) of coronary ostial lesions using the Szabo technique. BACKGROUND: When performing TRI of coronary ostial lesions, precise stent positioning is of paramount importance. TRI has experienced increasing popularity in the U.S.; however, utilization of the Szabo technique has not been systematically evaluated in this setting. We report the results of ostial stent deployment using the Szabo technique for 2 experienced TRI operators and centers. METHODS: This was a retrospective analysis of 40 consecutive patients who underwent PCI from April 2009 to September 2011. All patients who underwent PCI via the transradial route with the Szabo technique for ostial lesions performed by experienced transradial operators (>200 cases/yr) were included. RESULTS: In our study of 40 patients with 41 coronary ostial lesions, overall procedural success rate was 100%. Stent dislodgement was seen in 1 patient. Clinical follow up was 100%, with a mean duration of 292.7±200 days. Target lesion revascularization (TLR) was seen in 2 patients (5%). One patient had an episode of transient ischemic attack (TIA) at 33 days after PCI; another experienced subacute stent thrombosis at 81 days while on dual antiplatelet therapy. MACE was 7.5% overall. CONCLUSION: In our study, treatment of coronary ostial lesions with the Szabo technique via TRI is associated with a high procedural success rate and a low MACE of 7.5%.

Transradial cardiac catheterization: a review of access site complications.

Transradial catheterization (TRC) has been associated with a lower incidence of major access site related complications as compared to the transfemoral approach. With the increased adoption of transradial access, it is essential to understand the potential major and minor complications of TRC. The most common complication is asymptomatic radial artery occlusion, which rarely leads to clinical events, owing to the dual collateral perfusion of the hand. Adequate anticoagulation, appropriate compression techniques, and smaller sheath size can minimize the risk of radial artery occlusion. Hand ischemia with necrosis has never been reported during TRC with thorough pre-examination of intact collateral circulation. Radial artery spasm is relatively common, and can result in access and procedural failure. It can be prevented by the use of vasodilator cocktails and hydrophilic sheaths. Radial artery perforation can lead to severe forearm hematoma and compartment syndrome if not managed promptly. Careful observation, prompt detection of the hematoma, and management with a pressure bandage dressing are critical to avoid serious complications. Pseudoaneurym and arteriovenous fistula are rare complications, which can likely be managed conservatively without surgical intervention. Nerve injury occurring during access has been reported. Close observation for improvement is necessary, although symptoms usually improve over time. In summary, to prevent access site complications, avoidance of multiple punctures, gentle catheter manipulation, use of guided compression, coupled with careful observation for adverse warning signs such as hematoma, loss of pulse, pain, are critical for safe and effective TRC.

Embolic implications of combined risk factors in patients with patent foramen ovale (the CARPE criteria): consideration for primary prevention closure?

BACKGROUND: Large patent foramen ovale (PFO), spontaneous right-to-left shunt, large atrial septal aneurysm (ASA), coagulation abnormalities, and prominent eustachian valve (EV) have all been independently suggested as risk factors for recurrent stroke. We sought to retrospectively evaluate risk of stroke and impact of transcatheter PFO closure in patients with concurrent large PFO, spontaneous right-to-left shunt, large ASA, coagulation abnormalities, and prominent EV. METHODS: Between March 2006 and October 2008, 36 (mean age 44 +/- 10.9 years, 28 females) out of 120 consecutive patients referred to our center for transcatheter PFO closure had concomitant diagnosis of (a) large PFO on transcranial Doppler (TCD) and transesophageal echocardiography (TEE), (b) spontaneous right-to-left shunt on TCD, (c) large ASA, (d) prominent EV, and (e) coagulation abnormalities. All patients fulfilled the standard current indications for transcatheter closure and underwent preoperative TEE and brain magnetic resonance imaging (MRI), with subsequent intracardiac echocardiographic-guided transcatheter PFO closure. RESULTS: Compared to the remaining PFO population in the same period, patients with all five concomitant features had more ischemic brain lesions on MRI, previous history of recurrent stroke, more frequently a history of venous thromboembolism, and more severe migraine with aura. The concomitance of all the features confers the highest risk of recurrent stroke (OR 9.9, 3.0-18 [95% CI], P < 0.001). CONCLUSIONS: Despite its small sample size and nonrandomized retrospective nature, this is the first study to suggest that patients with concurrence of all the investigated characteristics have potentially a higher risk of stroke compared to controls. We thus propose the CARP criteria as a basis for further larger, longitudinal studies to assess the potential benefits of transcatheter closure in this patient subset in the absence of clinical recurrent stroke.

Ambulatory discharge after transradial coronary intervention: Preliminary US single-center experience (Same-day TransRadial Intervention and Discharge Evaluation, the STRIDE Study).

BACKGROUND: Although the safety and cost-effectiveness of same-day discharge after uncomplicated transradial percutaneous coronary intervention (TR-PCI) is well established in Europe and Asia, such data are not available for US patients. METHODS: All patients who underwent TR-PCI at our high-volume US medical center between 2004 and 2007 were included in this study. The primary end point was in-hospital adverse clinical outcomes between 6 and 24 hours postprocedure. RESULTS: A total of 450 patients were included in this study (aged 59 +/- 11 years). Of these, 13% were female, 27% were diabetic, 6% had peripheral vascular disease, and 5% had chronic kidney disease. Procedural indications included stable angina (49%), unstable angina (31%), non-ST elevation myocardial infarction (NSTEMI) (17%), and ST elevation myocardial infarction (STEMI) (3%). All patients received an intra-arterial cocktail of heparin, verapamil, and nitroglycerin, and 13% of patients received glycoprotein IIb/IIIa inhibitors. Seven percent of patients had 3-vessel disease, 3% had bypass grafts stenoses, and 20% had class B(2)/C lesions. Procedural success rate was 96%. A total of 24 (5.3%) postprocedural complications were observed; however, none occurred between hours 6 to 24, the time differential between same-day and next-day discharge. Thirteen patients (2.9%) experienced significant complications within the first 6 hours (MI, urgent repeat revascularization, and ventricular tachycardia). Eleven (2.4%) spontaneously resolved minor access complications developed. There were 12 same-day discharges according to the operators' discretion; none required readmission. CONCLUSIONS: Although a low incidence of complications did occur, none would have been impacted by same-day discharge. Those observed before 6 hours would have prevented early discharge, and those occurring after 24 hours would have been unaffected by routine next-day discharge. This observational study demonstrated the safety and feasibility for a prospective evaluation of ambulatory TR-PCI in an American practice setting.

Safety and efficacy of the drug-eluting stent: a double-edged sword?

Like the introduction of bare metal stents (BMS), that of drug-eluting stents (DES) represented a quantum leap in the interventional cardiology community's ongoing efforts to conquer restenosis. However, recent concerns over late thrombosis (LT) have tempered the initial enthusiasm. Nonetheless, when compared with BMS, the slightly higher DES-LT is counterbalanced by the device's markedly lower incidence of restenosis, resulting in net equivalent rates of death, myocardial infarction, and overall major adverse cardiovascular events. This article summarizes for the noncardiology practitioner the benefits and risks of DES, as well as essentials of postprocedural care of the DES patient. We discuss the pathophysiology of stent thrombosis, pivotal DES trials, and adjunct antiplatelet pharmacology. In December 2006, the Food and Drug Administration convened an expert panel to review these devices. Their recommendations, as well as the joint statement from the American College of Cardiology/American Heart Association/Society of Cardiovascular Angiography and Interventions, are outlined.

Current State of Bioabsorbable Polymer-Coated Drug-Eluting Stents.

Drug-eluting stents (DES) have been shown to significantly reduce clinical and angiographic restenosis compared to bare metal stents (BMS). The polymer coatings on DES elute antiproliferative drugs to inhibit intimal proliferation and prevent restenosis after stent implantation. Permanent polymers which do not degrade in vivo may increase the likelihood of stent-related delayed arterial healing or polymer hypersensitivity. In turn, these limitations may contribute to an increased risk of late clinical events. Intuitively, a polymer which degrades after completion of drug release, leaving an inert metal scaffold in place, may improve arterial healing by removing a chronic source of inflammation, neoatherosclerosis, and/or late thrombosis. In this way, a biodegradable polymer may reduce late ischemic events. Additionally, improved healing after stent implantation could reduce the requirement for long-term dual antiplatelet therapy and the associated risk of bleeding and cost. This review will focus on bioabsorbable polymer-coated DES currently being evaluated in clinical trials.

Phosphorylated STAT5 regulates p53 expression via BRCA1/BARD1-NPM1 and MDM2.

Signal transducer and activator of transcription 5 (STAT5) and nucleophosmin (NPM1) are critical regulators of multiple biological and pathological processes. Although a reciprocal regulatory relationship was established between STAT5A and a NPM-ALK fusion protein in T-cell lymphoma, no direct connection between STAT5 and wild-type NPM1 has been documented. Here we demonstrate a mutually regulatory relationship between STAT5 and NPM1. Induction of STAT5 phosphorylation at Y694 (P-STAT5) diminished NPM1 expression, whereas inhibition of STAT5 phosphorylation enhanced NPM1 expression. Conversely, NPM1 not only negatively regulated STAT5 phosphorylation but also preserved unphosphorylated STAT5 level. Mechanistically, we show that NPM1 downregulation by P-STAT5 is mediated by impairing the BRCA1-BARD1 ubiquitin ligase, which controls the stability of NPM1. In turn, decreased NPM1 levels led to suppression of p53 expression, resulting in enhanced cell survival. This study reveals a new STAT5 signaling pathway regulating p53 expression via NPM1 and uncovers new therapeutic targets for anticancer treatment in tumors driven by STAT5 signaling.

Left Atrial Appendage Closure -The WATCHMAN Device.

Atrial fibrillation (AF) is one of the most common arrhythmias seen in clinical cardiology practice. Patients with non-valvular AF have an approximately 5-fold increase in the risk of stroke, with an exponential increase with advancing age. Cardioembolic strokes carry a high mortality risk. Although the potential of warfarin to reduce systemic embolization in AF patients is well established, its use is difficult due to narrow therapeutic windows and additional complications (e.g. increased risk of bleeding), especially for aging patients. Therefore, alternative means of treatment to reduce stroke risk in these patients are needed. The left atrial appendage is the major source of thrombus formation in patients with non-valvular AF. The WATCHMAN device (Boston Scientific, MA) is a percutaneous left atrial appendage closure device which has been tested prospectively in multiple randomized trials. It offers a new stroke risk reduction option for high-risk patients with non-valvular atrial fibrillation who are seeking an alternative to long-term warfarin therapy. Based on the robust WATCHMAN clinical program which consists of numerous studies, with more than 2,400 patients and nearly 6,000 patient-years of follow-up, the WATCHMAN LAAC Device is approved by FDA. In this article we reviewed the preclinical studies and clinical trials, as well as the next generation of the device.

Five-year follow-up of intracardiac echocardiography-assisted transcatheter closure of complex ostium secundum atrial septal defect.

OBJECTIVE: We sought to prospectively evaluate long-term follow-up results of intracardiac echocardiography-aided transcatheter closure of complex atrial septal defects (ASD) in the adults. DESIGN AND SETTINGS: Prospective multicenter registry in tertiary care hospitals. PATIENTS AND INTERVENTIONS: Over a 5-year period, we prospectively enrolled 56 patients (mean age 49 ± 16.7 years, 24 females) who have been referred to our center for catheter-based closure of complex secundum ASD (> 25 mm diameter, deficiency of ≥ 1 rim, multiple secundum ASD, multiperforated ASD, associated incomplete floor of the fossa ovalis with or without aneurysm, embryonic remnants of incomplete atrial septation). All patients were screened by means of transesophageal echocardiography before the operation. Eligible patients underwent intracardiac echocardiography study and closure attempt. RESULTS: Forty patients underwent a transcatheter closure attempt: transesophageal echocardiography-planned device type and size were modified in 32 patients (64%). Rates of procedural success, predischarge occlusion, and major complications rate were 100%, 90%, and 2%, respectively. On mean follow-up of 5.4 ± 1.8 years, the follow-up occlusion rate was 98%. During follow-up, only one case of permanent atrial fibrillation was observed. There were no cases of aortic/atrial erosion, device thrombosis, or new atrioventricular valve dysfunction. CONCLUSIONS: Intracardiac echocardiography-guided complex secundum ASD transcatheter closure is safe and effective and appears to have excellent long-term results, thus minimizing potential complications resulting from the complex anatomy.

Long-term results of the amplatzer cribriform occluder for patent foramen ovale with associated atrial septal aneurysm: impact on occlusion rate and left atrial functional remodelling.

BACKGROUND: Treatment of patients with concomitant patent foramen ovale (PFO) and atrial septal aneurysm (ASA) poses a number of challenges; while some authors have suggested the off-label use of the Amplatzer Cribriform Occluder in such anatomy, the long-term outcomes of this strategy is unknown. Our study aimed to assess the long-term impact on closure rate, left atrial functional remodelling, and clinical outcomes of off-label implantation of Amplatzer ASD Cribriform Occluder in patients with PFO and ASA. METHODS: We prospectively enrolled 160 consecutive patients with previous stroke (mean age 36 ± 9.5 years, 109 females), significant PFO and ASA. All patients were treated with Amplatzer Cribriform Occluder to ensure the most complete possible coverage of the ASA. Residual shunt and LA passive and active emptying, LA conduit function, and LA ejection fraction were computed before and after 6 months from the procedure and then yearly. All patients underwent successful transcatheter closure (mean ratio device/diameter of interatrial septum = 0.74). RESULTS: Incomplete ASA coverage during intraprocedural intracardiac echocardiography was observed in 71 patients. During mean follow-up of 3.6 ± 1.8 years, when compared to patients with complete coverage, there were no differences in LA functional parameters and complete occlusion achieved in 150/160 patients (93.7%). No new cerebral ischemic events, aortic erosions or device thrombosis were recorded during the follow-up. CONCLUSIONS: THE USE OF THE AMPLATZER ASD CRIBRIFORM TO TREAT PFO AND ASSOCIATED ASA SEEMS SAFE AND EFFECTIVE: relatively small Occluder devices are probably effective enough to promote left atrial functional remodelling.

Vasomotor function and re-endothelialisation after implantation of biodegradable abluminal polymer coated paclitaxel-eluting stents in rabbit iliac arteries: a time-course study.

AIMS: To evaluate the time-course of vasomotor function and re-endothelialisation after implantation of a novel platinum-chromium (PtCr) abluminal biodegradable polymer-coated paclitaxel-eluting stent (PES, Labcoat Element) in rabbit iliac arteries. METHODS AND RESULTS: Either PES (n=18) or an identical platform of bare metal stents (BMS, Element, n=18) were implanted in rabbit iliac arteries (six animals per time-point). At 14, 30, and 90 days, acetylcholine- and nitroglycerine-induced vasomotor reactivity at 5-10 mm distal to the stent was measured. Subsequently, the animals were terminated. The stented artery was bisected longitudinally for either SEM or en face CD31 immunochemistry examination. All arteries were patent with normal angiographic flow. Decreased endothelial-dependent vasomotion was found at both 14 and 30 days for PES compared to BMS (p<0.01, respectively); however, these differences resolved by 90 days. Endothelial-independent vasorelaxation was similar at all three time-points. Both SEM and en face staining demonstrated equivalent endothelial coverage on the surface of the stented segments above and between struts at all time-points. CONCLUSIONS: This novel bioabsorbable polymer abluminal-coated PES demonstrated vasomotor function comparable to BMS within three months post-deployment in the rabbit iliac model. Despite indistinguishable endothelial cell coverage on the stent surface between groups, earlier differences in vasomotion were detected: this finding suggests that the timing of restoration vasomotor function lags morphologic endothelial recovery.

Nobori stent shows less vascular inflammation and early recovery of endothelial function compared with Cypher stent.

OBJECTIVES: The current study sought to examine inflammation at the stented segments of Nobori (Terumo Corporation, Tokyo, Japan) and Cypher (Cordis, Miami, Florida) drug-eluting stents (DES), as well as free radical production and endothelial function of the adjacent nonstented segments in a pig coronary model. BACKGROUND: Nobori is a novel DES, incorporating a biolimus A9-eluting biodegradable polymer coated only on the abluminal surface of the stent. These unique features may favorably affect inflammation and endothelial function, as compared to the currently marketed DES. Presently, pre-clinical data on direct comparison of the various generations of DES are not available. METHODS: A total of 18 DES were implanted in pig coronary arteries and subsequently explanted at 1 month. Stented segments were assessed by angiography and histology. Ex vivo vasomotor function and superoxide production in segments proximal and distal to the stent were determined. The vasoconstriction, endothelial-dependent relaxation, and endothelial-independent relaxation of proximal and distal nonstented segments were measured. RESULTS: Histological evaluation revealed lower inflammatory response with Nobori than with Cypher DES. There is trend for lower angiographic percentage diameter stenosis in Nobori versus Cypher groups (p = 0.054). There was increased endothelium-dependent relaxation, decreased endothelin-1-mediated contraction, and less superoxide production in the vessel segments proximal and distal to Nobori versus Cypher stents. CONCLUSIONS: Our data show significantly lower inflammatory response in the stented segments, and rapid recovery of endothelial function of peristent segments in the Nobori group compared with Cypher DES group at 1 month in porcine coronary artery model.