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Intravascular lithotripsy (IVL) has been well characterized as a safe and effective method for plaque modification in the treatment of de-novo, calcific coronary artery disease. In-stent restenosis (ISR) remains a major challenge in coronary revascularization, especially "multilayer" ISR. The use of IVL in ISR remains off-label and has been described in case reports and small case series. We report the single-center experience using IVL for the treatment of ISR, including multilayer ISR.This was a retrospective single-center study. All intracoronary percutaneous interventions requiring lithotripsy use, between May 2021 and December 2021, were reviewed. We selected only the cases involving IVL use for the treatment of in-stent restenosis. Baseline characteristics of patients were obtained from chart review. Procedural details and outcomes were obtained from reports and from a detailed review of procedural images.A total of 13 ISR lesions were treated with IVL, of which 5 were in cases of multilayer ISR. Procedural success was observed in 11 lesions. Three patients had recurrent angina during a mean follow-up of 133 days. None of the patients had hard outcomes of myocardial infarction or cardiac death during the follow-up period.IVL is feasible and safe for ISR treatment including multilayer ISR. IVL is associated with good immediate procedural success, and a low rate of short-term adverse outcomes.

Coronary artery perforation is a serious complication during percutaneous coronary intervention that results in significant increase in morbidity and mortality. In this article, we provide a state-of-the-art overview of the contemporary management of coronary perforation and the possible scenarios that operators may run into during percutaneous coronary interventions.Coronary perforation during percutaneous coronary intervention. Literature search was performed using PubMed and Google Scholar to identify the most recently published articles covering this topic.As part of this review, we also provide an expert commentary discussing the nuances in the recognition and management of coronary artery perforation, in addition to future directions, and improvements in technology that could make the management of coronary perforation safer and more effective.

While poor drug adherence is frequent in patients with resistant hypertension, detailed analyses of the impact of drug adherence on the success of renal denervation are scarce. We report drug adherence at baseline, changes in drug adherence, and the influence of these parameters on blood pressure changes at 6 and 12 months in patients treated with alcohol-mediated renal denervation as part of the Peregrine study. Urinary detection of antihypertensive drugs was performed using high-performance liquid chromatography-tandem mass spectrometry. Full adherence, partial adherence, and complete non-adherence were defined as 0, 1, or ≥2 drugs not detected, respectively. Renal denervation was performed in 45 patients with uncontrolled hypertension on ≥3 antihypertensive medications (62% men, age 55 ± 10 years). At baseline, the proportion of fully, partially, and non-adherent patients was 62% (n = 28), 16% (n = 7), and 22% (n = 10), respectively. At 6 months, adherence improved by 21% (n = 9), remained unchanged at 49% (n = 21), and worsened by 30% (n = 13). Mean 24-h systolic blood pressure decreased by 10 ± 13, 10 ± 4, and 14 ± 19 mmHg in fully, partially, and non-adherent patients (p = 0.77), and by 14 ± 14, 8 ± 11, and 14 ± 18 mmHg in patients who improved, maintained, or decreased adherence, respectively (p = 0.35). The results at 12 months were similar. About 40% of patients with apparently treatment-resistant hypertension were not fully adherent at baseline, and adherence decreased further in 30%. Nevertheless, mean blood pressure changes after renal denervation were similar irrespective of drug adherence. Our results suggest that such patients may benefit from alcohol-mediated renal denervation, irrespective of drug adherence. These findings are hypothesis-generating and need to be confirmed in ongoing sham-controlled trials.

The SLENDER Integrated Delivery System (IDS™) is an ‘all-in-one’ fixed-wire coronary stenting device designed for direct stenting, precluding the need for conventional guidewires and predilatation balloons. It achieves ultra-low profiles (crossing profiles as low as 0.029″/0.737 mm), enabling the downsizing of catheters to facilitate transradial intervention in a large subsets of patients. The IDS represents the first advance in coronary stent delivery since the introduction of rapid-exchange stent delivery systems >20 years ago. SLENDER IDS has demonstrated non-inferiority compared with commercial DES , excellent long-term safety and a potentially more efficient approach to PCI where patient comfort is enhanced, procedures are streamlined, and resource consumption is reduced. This paper will summarize the novel features of this new stent delivery system and the early clinical data demonstrating safety and efficacy.

OBJECTIVES: The current analysis utilized core laboratory angiographic data from a prospective, single-arm, open-label, multi-center feasibility study to ascertain whether the location of alcohol infusion within main renal arteries during renal denervation (RDN) had an impact on the BP-lowering effect at 6 months. BACKGROUND: The influence of the location of alcohol infusion during RDN, within the main renal artery (proximal, middle, or distal), on the magnitude of the blood pressure (BP) lowering is unstudied. METHODS: The Peregrine Catheter was used to perform alcohol-mediated RDN with an infusion of 0.6 mL of alcohol per artery as the neurolytic agent in 90 main arteries and four accessory arteries of 45 patients with hypertension. RESULTS: No relationship between the site of alcohol infusion and change from baseline in both office systolic and 24-hour systolic ambulatory BP (ABP) at 6 months was observed. When analyzed at the artery level, the least squares (LS) mean changes ± SEM from baseline to 6 months post-procedure in 24-hour systolic ABP when analyzed by renal arterial location were -11.9 ± 2.4 mmHg (distal), -10 ± 1.6 mmHg (middle), and -10.6 ± 1.3 mmHg (proximal) (all p < 0.0001 for change from baseline within groups). The results were similar for office systolic BP. There was no difference between treated locations (proximal is reference). CONCLUSION: In this post-hoc analysis, the location of alcohol infusion within the main renal artery using the Peregrine system, with alcohol as the neurolytic agent for chemical RDN, did not affect the magnitude of BP changes at 6 months.

Sympathetic nervous system activation in patients with heart failure is one of the main pathophysiologic mechanisms associated with the worse outcomes. Pharmacotherapies targeting neurohormonal activation have been at the center of heart failure management. Despite the advancement of therapies and the available treatments, heart failure continues to have an overall poor prognosis. Renal denervation was originally developed to lower systemic blood pressure in patients with poorly controlled hypertension, by modulating sympathetic outflow. However, more recently, multiple studies have investigated the effect of renal denervation in heart failure patients with both preserved (HFpEF) and reduced ejection fractions (HFrEF). This paper provides an overview of the potential effect of renal denervation in altering the various pathophysiologic, sympathetically mediated pathways that contribute to heart failure, and reviews the literature that supports its future use in those patients.

A 79-year-old woman presented with new-onset heart failure. She had pleural effusion, pericardial effusion, and an ejection fraction of 35% on echocardiogram. Her coronary angiogram revealed mild coronary artery disease (CAD). However, initially unexplained extravasation of the contrast was also seen in the cranial view during angiogram. The decision was made to medically manage CAD, but she remained tachycardic, with borderline low blood pressure. After a series of complications and tests, clearance of contrast from the stomach was confirmed. This represents an unusual case in which fluoroscopy revealed active gastric bleeding with contrast extravasation during coronary angiography.

Primary percutaneous coronary intervention (PPCI) has dramatically changed the outcome of patients with ST-elevation myocardial infarction (STEMI). However, despite improvements in interventional technology, registry data show little recent change in the prognosis of patients who survive STEMI, with a significant incidence of cardiogenic shock, heart failure, and cardiac death. Despite a technically successful PPCI procedure, a variable proportion of patients experience suboptimal myocardial reperfusion. Large infarct size and coronary microvascular injury, as the consequence of ischaemia–reperfusion injury and distal embolization of atherothrombotic debris, account for suboptimal long-term prognosis of STEMI patients. In order to address this unmet therapeutic need, a broad-range of device-based treatments has been developed. These device-based therapies can be categorized according to the pathophysiological pathways they target: (i) techniques to prevent distal atherothrombotic embolization, (ii) techniques to prevent or mitigate ischaemia/reperfusion injury, and (iii) techniques to enhance coronary microvascular function/integrity. This review is an overview of these novel technologies with a focus on their pathophysiological background, procedural details, available evidence, and with a critical perspective about their potential future implementation in the clinical care of STEMI patients.

Background Arterial hypertension is a common and life-threatening condition and poses a large global health burden. Device-based treatments have been developed as adjunctive or alternative therapy, to be used with or without antihypertensive medication for treating uncontrolled hypertension. The safety and feasibility of chemical renal denervation (RDN) using the Peregrine Catheter and alcohol were demonstrated in a first-in-man and open-label clinical trials, prompting the initiation of the ongoing TARGET BP OFF-MED and TARGET BP I trials. Design The TARGET BP trials are randomized, blinded, sham-controlled trials designed to assess the safety and efficacy of alcohol-mediated RDN for the treatment of uncontrolled hypertension in the absence of antihypertensive medications (TARGET BP OFF-MED) or in addition to prescribed antihypertensive medications (TARGET BP I). Subjects with confirmed uncontrolled hypertension and suitable renal artery anatomy are randomized (1:1) to receive either RDN using the Peregrine Kit with alcohol (0.6 mL per renal artery) infused through the Peregrine Catheter or diagnostic renal angiography only (sham procedure). TARGET BP OFF-MED completed enrollment and randomized 96 subjects. TARGET BP I will randomize approximately 300 subjects and will transition to an open-label safety cohort of approximately 300 subjects receiving RDN once the primary efficacy endpoint of the Randomized Controlled Trial (RCT) cohort has been met. Primary endpoints are change in mean 24-hour ambulatory systolic blood pressure from baseline to 8 weeks (TARGET BP OFF-MED) and 3 months (TARGET BP I) post-procedure. Conclusion The TARGET BP trials are the first large-scale, international, randomized trials aimed to investigate the safety and BP lowering efficacy of a novel RDN method, with perivascular alcohol delivery using the Peregrine Kit.

Guide catheter extension is an integral part of percutaneous coronary intervention (PCI). First generation guide catheter extension devices are monorail, blunt ended tubular structures with limitations. The CrossLiner™ is a next generation guide extension "system" intended to allow safe, deep, coronary intubation.The CrossLiner was tested in a head-to-head study with the GuideLiner™ and GuideZilla™ in a porcine coronary model, with stenting. Data were collected from 8 coronary vessels from four animals, to evaluate the ability to deeply intubate the vessel with the guide extension.The CrossLiner crossed distally and through a distal stented segment in 8/8 vessels, while the first-generation devices were stuck proximal to the stent (n=2/8) or at the stent edge (n=4/8), or passed partially into the deployed stent with difficulty (2/8) vessels (p 0.0002 for deliverability). The average depth of guide extension delivery/ "intubation" was 12.9±3.6 cm for the CrossLiner and 5.6±1.1 cm for the first-generation guide extension (p 0.001).The CrossLiner is a next generation guide extension system that may offer advantages over first generation devices. Further clinical evaluation will be required to assess the role of this new device in PCI.

Catheter-based renal denervation (RDN) has been investigated for hypertension (HTN) treatment with variable success. One of the novel approaches to RDN is the delivery of micro-doses of dehydrated alcohol to the adventitial space of the renal artery to perform perivascular ablation of the sympathetic nerves. We sought to assess the safety and efficiency of transcatheter alcohol-mediated perivascular renal denervation in patients with resistant hypertension. Fifty adult patients who had been referred for resistant HTN were screened. To qualify for the study, the patients had to have a mean 24 h systolic pressure &ge, 135 mmHg based upon ambulatory blood pressure monitoring (ABPM) and acceptable renal artery anatomy confirmed by the contrast computer tomography (AngioCT) and nephrologist consultation. Ten patients were eligible for chemical RND. There were no safety issues throughout the 24 months of follow-ups. The mean decrease in the office BP (OBP) was significant during 24 months of follow-up (p &lt, 0.01). The difference in the BP in the ABPM was statistically significant in the 1st, 3rd and 12th months (p &lt, 0.01), whereas during the 3-month follow-up, a trend was observed. The modifications of anti-hypertension drugs throughout the follow-up period were minimal. This study has shown that transcatheter alcohol-mediated renal denervation in patients with resistant hypertension is feasible and safe. Nevertheless, it is a hypothesis-generating study.

Renal sympathetic denervation using conventional non-irrigated radiofrequency catheters has potential technical shortcomings, including limited penetration depth and incomplete circumferential nerve damage, potentially impacting therapeutic efficacy. Against this background, second generation multi-electrode, radiofrequency and ultrasound renal denervation systems have been developed to provide more consistent circumferential nerve ablation. Irrigated catheters may allow deeper penetration while minimizing arterial injury. In this context, catheter-based chemical denervation, with selective infusion of alcohol, a potent neurolytic agent, into the perivascular space, may minimize endothelial, intimal and medial injury while providing circumferential neurolysis. Animal studies demonstrate pronounced renal norepinephrine level reductions and consistent renal nerve injury after perivascular alcohol infusion using the Peregrine Catheter. Early clinical studies demonstrated significant blood pressure reductions and a reasonable safety profile. Randomized sham-controlled trials (NCT03503773, NCT02910414) are underway to examine whether the aforementioned theoretical advantages of alcohol-medicated denervation with the Peregrine System™ Kit translate into clinical benefits.

Supplemental Digital Content is available in the text., Background: Primary results of this prospective, open-label, multicenter trial suggested that alcohol-mediated renal denervation with perivascular injection of dehydrated alcohol using the Peregrine System Infusion Catheter safely reduces blood pressure (BP) in patients with resistant hypertension. To date, maintenance of the BP-lowering effect beyond 6 months using this novel technology has not been reported. This article describes the final, 12-month follow-up data on the safety and efficacy of alcohol-mediated renal denervation in these patients. Methods: Forty-five patients with resistant hypertension on a stable regimen of on average 5.1±1.5 antihypertensive medications underwent successful bilateral renal denervation using the Peregrine Catheter with alcohol as the neurolytic agent (0.6 mL per renal artery). Apart from 2 vascular access pseudoaneurysms (both without sequelae), no major procedural complications occurred. Results: At 12 months post-procedure, mean 24-hour ambulatory systolic and diastolic BP were reduced by 10 mm Hg (95% CI, −16 to −5) and 7 mm Hg (−10 to −3), respectively (P

Objectives This study evaluated the first clinical use of a new endovascular approach to renal denervation, using chemical neurolysis, via periadventitial infusion of dehydrated alcohol (ethanol) to perform “perivascular” renal artery sympathetic denervation. Background Renal denervation remains a promising technology for the treatment of hypertension and other disorders. Methods A novel 3-needle delivery device (Peregrine System Infusion Catheter, Ablative Solutions, Inc., Kalamazoo, Michigan) was introduced into the renal arteries of 18 subjects with refractory hypertension. Microdoses of alcohol were infused bilaterally via the 3 needles into to the adventitial space (0.30 ml/artery, 37 arteries). Renal artery angiography was performed at the time of the procedure and at 6 months (n = 16). The primary safety endpoints were complications associated with the catheter insertion and delivery of the neurolytic agent or any major vascular access complications. The secondary performance endpoint was a reduction in office-based systolic blood pressure at 6 months compared with baseline. Results Procedural success was achieved in 100% of subjects (N = 18) and arteries (N = 37). There were no study-related adverse clinical events at follow-up. One death of a subject was recorded but determined by the investigator and an independent medical monitor to be non–study related. There were no angiographic observations of renal artery stenosis, aneurysms, or other renal artery abnormalities at 6 months (32 renal arteries). Sixteen of the 18 subjects had a 6-month follow-up. The mean office systolic blood pressure decreased from 175 ± 17 mm Hg to 151 ± 26 mm Hg (−24 mm Hg). There was an average reduction of antihypertensive medications from 3.4 (baseline) to 2.0 per subject at 6 months. Conclusions Chemical renal denervation using the infusion of very low doses of alcohol directly into the adventitial space appears to be feasible and safe. This approach may be a promising alternative approach to perform catheter-based renal denervation. These results need to be confirmed in larger scale clinical studies.

Background/PurposeWe update the pre-clinical and early clinical results using a novel endovascular approach, to perform chemical renal denervation, via peri-adventitial injection of micro-doses of dehydrated alcohol (ethanol–EtOH).Methods/MaterialsA novel, three-needle delivery device (Peregrine™) was used to denervate the renal arteries of adult swine (n=17) and in a first-in-man feasibility study (n=18). In the pre-clinical testing EtOH was infused bilaterally with one infusion per renal artery into to the perivascular space, using EtOH doses of 0.3ml/artery (n=8), and 0.6ml/artery (n=9), and with saline sham control (0.4ml/artery n=3). Renal parenchymal norepinephrine (NE) concentration (performed blindly), and safety were the primary endpoints. Data from the first-in-man study (n=18) to evaluate device performance, safety and peri-procedural pain are reported.ResultsIn the pre-clinical testing renal function was unchanged at 3-month follow-up. Angiography at 90days (n=34 arteries) demonstrated normal appearing renal arteries, unchanged from baseline, and without stenosis or other abnormalities. The reductions in mean renal parenchymal NE reductions at 3months were 68% and 88% at doses of 0.3 and 0.6ml, respectively (p

Significant improvements in door-to-balloon times have led to a reduction in mortality in ST-segment elevation myocardial infarction; however, mean symptom-to-door times remain at 2 to 3 hours. An intracardiac electrogram monitoring device may be beneficial in high-risk patients by alerting them to rapidly progressive ST-segment changes indicative of acute coronary occlusion. The Cardiosaver and DETECT phase I clinical studies demonstrated the safety, feasibility, and potential benefit of using an intracardiac electrogram monitoring device to alert the patient to seek medical attention. The goal of the randomized, prospective ALERTS Trial (Clinicaltrials.gov no. NCT00781118) is to evaluate the efficacy of an implantable monitoring device (IMD) in reducing the composite of either cardiac or unexplained death, new Q-wave myocardial infarction, or symptom-to-door time of >2 hours for confirmed thrombotic events. The IMD alerts the patient in real time when ST-segment deviation from a personalized baseline exceeds the trigger threshold. The trial is designed to enroll high-risk post‐acute coronary syndrome patients or patients with previous multivessel coronary artery bypass surgery. All patients have the IMD implanted, with 1:1 unblinded randomization to the alerting feature being either turned on versus turned off for the first 6 months. Randomization occurs at the first follow-up visit, 7 to 14 days after the implantation of the IMD. Subjects then return for follow-up visits at months 1, 3, and 6 and thereafter every 6 months until closure of the investigational device exemption. Subjects who cannot be implanted successfully or who have the device explanted are removed from the study and followed up for a minimum of 30 days post‐procedure. If a subject experiences a device-related complication and/or adverse experience, the subject is followed up until resolution or until the condition becomes stable and no further change is anticipated.

The Peregrine post-market study is a prospective, single arm, European trial evaluating the safety and performance of the Peregrine System™ Infusion Catheter (Ablative Solutions, San Jose, CA) to perform chemical (alcohol) renal denervation (cRDN) to treat resistant hypertension (rHTN). The study

The Peregrine post-market study is a prospective, single-arm, open label, multicenter European trial evaluating the safety and performance of the Peregrine System™ Infusion Catheter (Ablative Solutions Inc., Palo Alto, CA, USA) to perform chemical (alcohol) renal denervation (cRDN) to treat

This study investigates the performance of a new statistically driven acute ischemia detection algorithm that can process data from two bipolar cutaneous or subcutaneous leads. During a start-up phase, the algorithm processes electrocardiogram signals to determine a normal range of ST-segment deviation as a function of heart rate. The algorithm then generates upper and lower ST-deviation thresholds based on the dispersion of the baseline ST-deviation data. After the start-up phase, persistent ST-deviation that is beyond either the upper or lower thresholds results in detection of acute ischemia. To test the algorithm, we performed long-term (10 day) Holter monitoring in a control group of 14 subjects. We also performed Holter monitoring during balloon angioplasty, and for 2 days after surgery, in 30 subjects who underwent elective percutaneous coronary interventions ("PCI"). We determined the percentage of balloon inflations the algorithm detected without producing false positive detections within the control group 10-day daily life data. The algorithm detected 17/17 LAD occlusions, 7/8 LCX occlusions, and 8/9 RCA occlusions. Our results suggest that automatically generated, subject-specific, heart-rate dependent ST-deviation thresholds can detect PCI induced myocardial ischemia without resulting in false positive detections in a small control group.

Objectives We report the first clinical studies of intracardiac ST-segment monitoring in ambulatory humans to alert them to significant ST-segment shifts associated with thrombotic occlusion. Background Despite improvements in door-to-balloon times, delays in symptom-to-door times of 2 to 3 h remain. Early alerting of the presence of acute myocardial infarction could prompt patients to seek immediate medical evaluation. Methods Intracardiac monitoring was performed in 37 patients at high risk for acute coronary syndromes. The implanted monitor continuously evaluated the patients9 ST segments sensed from a conventional pacemaker right ventricle apical lead, and alerted patients to detected ischemic events. Results During follow-up (median 1.52 years, range 126 to 974 days), 4 patients had ST-segment changes of ≥3 SDs of their normal daily range, in the absence of an elevated heart rate. This in combination with immediate hospital monitoring led to angiogram and/or intravascular ultrasonography, which confirmed thrombotic coronary occlusion/ruptured plaque. The median alarm-to-door time was 19.5 min (6, 18, 21, and 60 min, respectively). Alerting for demand-related ischemia at elevated heart rates, reflective of flow-limiting coronary obstructions, occurred in 4 patients. There were 2 false-positive ischemia alarms related to arrhythmias, and 1 alarm due to a programming error that did not prompt cardiac catheterization. Conclusions Shifts exceeding 3 SD from a patient9s daily intracardiac ST-segment range may be a sensitive/specific marker for thrombotic coronary occlusion. Patient alerting was associated with a median alert-to-door time of 19.5 min for patients at high risk of recurrent coronary syndromes who typically present with 2- to 3-h delays.

Recent studies and editorials have stirred controversy and generated tremendous publicity in the lay press related to the safety of drug-eluting stents (DES) for the treatment of coronary artery disease. Questions have been raised regarding the risks of late, or very late stent thrombosis with DES. The purpose of this editorial and review of stent thrombosis is to illuminate some counterpoints to some of the attention surrounding the issues of late DES thrombosis. The risks of DES stent thrombosis versus BMS may have been overstated by flawed studies. Late stent thrombosis does occur with both BMS and DES, and may or may not be modestly higher with DES. The time course of very late “DES thrombosis,” suggests that peristent plaque ruptures and disease progression in the target vessel may cause some, or many of these events. There is still much to be learned about the biology of DES. Although there is a small risk of late thrombosis with DES, there is little question that this technology provides benefit to the vast majority of patients compared with prior revascularization strategies, using balloon angioplasty, BMS, or bypass surgery. Substantial resources should be devoted to creating more biocompatible DES systems, and to minimizing the risks of both early and late stent thrombosis. © 2007 Wiley-Liss, Inc.

Objective: To assess the safety and efficacy of direct stenting using the sirolimus-eluting BX Velocity™ stent in patients with coronary lesions. Background: Although direct coronary stenting has become a widespread practice, there have been no systematic assessments of direct stenting with drug-eluting stents. Methods: Total of 225 patients with identical inclusion and exclusion criteria as the original SIRIUS trial were enrolled in this prospective single-arm study. They were compared in a no-inferiority design with 412 similar patients from the SIRIUS trial who had sirolimus-eluting stents deployed after predilatation and were preassigned to angiographic follow-up evaluation. Results: Direct stenting was successful in 85.8% of the patients. Compared with the predilatation group, direct stenting was associated with shorter median procedure duration (33 min vs. 45 min, P < 0.001). Angiographic follow-up at 8 months revealed similar late loss (in-stent—0.19 ± 0.47 mm vs. 0.17 ± 0.44 mm, and in-lesion—0.23 ± 0.41 mm vs. 0.24 ± 0.47 mm) and similar frequency of binary restenosis (in-stent—4.6% vs. 3.2% and in-lesion—6.1% vs. 8.9%) between the two treatment strategies. However, stent-edge restenosis was lower with direct stenting than in the predilatation control group (2.1% vs. 6.9%, P = 0.02). At 12-months, there were no significant differences in target lesion revascularization (3.7% vs. 5.1%, P = ns) or composite major adverse cardiac events (7.0% vs. 8.3%, P = ns). Conclusions: In patients similar to those treated in the SIRIUS trial, direct stenting using sirolimus-eluting stents achieves excellent short- and long-term clinical and angiographic results with shorter procedure time and less frequent stent edge restenosis compared with predilation stent implantation techniques. © 2007 Wiley-Liss, Inc.

This study evaluated the first clinical use of a new endovascular approach to renal denervation, using chemical neurolysis, via periadventitial infusion of dehydrated alcohol (ethanol) to perform "perivascular" renal artery sympathetic denervation.Renal denervation remains a promising technology for the treatment of hypertension and other disorders.A novel 3-needle delivery device (Peregrine System Infusion Catheter, Ablative Solutions, Inc., Kalamazoo, Michigan) was introduced into the renal arteries of 18 subjects with refractory hypertension. Microdoses of alcohol were infused bilaterally via the 3 needles into to the adventitial space (0.30 ml/artery, 37 arteries). Renal artery angiography was performed at the time of the procedure and at 6 months (n = 16). The primary safety endpoints were complications associated with the catheter insertion and delivery of the neurolytic agent or any major vascular access complications. The secondary performance endpoint was a reduction in office-based systolic blood pressure at 6 months compared with baseline.Procedural success was achieved in 100% of subjects (N = 18) and arteries (N = 37). There were no study-related adverse clinical events at follow-up. One death of a subject was recorded but determined by the investigator and an independent medical monitor to be non-study related. There were no angiographic observations of renal artery stenosis, aneurysms, or other renal artery abnormalities at 6 months (32 renal arteries). Sixteen of the 18 subjects had a 6-month follow-up. The mean office systolic blood pressure decreased from 175 ± 17 mm Hg to 151 ± 26 mm Hg (-24 mm Hg). There was an average reduction of antihypertensive medications from 3.4 (baseline) to 2.0 per subject at 6 months.Chemical renal denervation using the infusion of very low doses of alcohol directly into the adventitial space appears to be feasible and safe. This approach may be a promising alternative approach to perform catheter-based renal denervation. These results need to be confirmed in larger scale clinical studies.

It is our pleasure to respond to the letter published by Dr. Toutouzas and colleagues in reference to our paper describing the first-in-human experience with the Peregrine System for chemical renal denervation (RDN) [(1)][1]. We appreciate their enthusiasm for the concept and acknowledge their

Background— Stent thrombosis is an infrequent complication of intracoronary stenting that often has devastating clinical consequences. This study assesses the additional benefit of heparin coating with the BX VELOCITY Balloon-Expandable Stent with HEPACOAT, Carmeda end-point attached heparin (HEPACOAT) in patients with de novo or restenotic native coronary artery lesions treated with aspirin monotherapy after optimal stenting. Methods and Results— This was a multicenter, prospective, nonrandomized, pilot study. Two hundred patients (69% men; mean age, 64.1±11.2 years) meeting the eligibility criteria were treated with the HEPACOAT stent and aspirin alone after stenting. Any other antiplatelet or anticoagulation therapy was not permitted. Procedural success was achieved in all patients. There were 3 postprocedural non–Q-wave myocardial infarctions. The primary end point of stent thrombosis at 30 days occurred in 2 of 200 patients (1%): in one after blunt chest trauma and in the other in the setting of essential thrombocytosis. Major adverse cardiac events (death, myocardial infarction, target lesion revascularization, and coronary artery bypass grafting) were observed at 30 days in 5 of 200 (2.5%) patients. Conclusions— The BX VELOCITY stent with HEPACOAT and aspirin alone after the procedure was safe in select patients with de novo or restenotic lesions in native coronary arteries. Heparin coating provides additional protection against stent thrombosis.

In the 1930s–1950s surgical renal sympathectomy was used to treat severe hypertension [1–3]. Despite a successful lowering of blood pressure (BP) observed with surgical denervation, this technique was abandoned due to a relatively high morbidity and mortality, and as a result of the development of more effective oral antihypertensive medications

Although manufacturers' compliance tables of stent delivery balloons indicate the diameter of the balloon at a given inflation pressure, it is unclear whether these data correlate with in vivo true intracoronary balloon diameters (TBDs). The TBDs of two new-generation balloon-expandable stent delivery systems (Duet and NIR) were measured by quantitative coronary analysis (QCA) in 100 consecutive patients. The manufacturers' stated balloon diameter (BD) of the stent delivery systems overestimated the TBD in 94% +/- 4% of patients receiving both Duet or NIR stent implantations. In only 6% of the patients, the TBD matched the manufacturers' stated balloon diameter. There was no underestimation of TBDs by both manufacturers' compliance tables. The Duet tables overestimated TBDs by 14% +/- 8% (range, 1%-36%), the NIR tables by 18% +/- 8% (range, 1%-41%), P < 0.05, Duet vs. NIR, respectively. When the manufacturers' data were corrected for the differences in reporting data from in vitro tests, i.e., balloon compliance data with or without the stent, the degree of overestimation of diameters was similar for Duet and NIR stent delivery balloons (14% +/- 8% vs. 13% +/- 7%, Duet vs. NIR; P = NS). Manufacturers' compliance tables of both the Duet and NIR stent delivery balloon systems significantly overestimate the true intracoronary balloon diameter. The manufacturers' of stent delivery balloons should clearly state on the box, if balloon compliance data were derived from in vitro bench testing, which phantoms were used for compliance analysis, and that the tables may overestimate the true intracoronary balloon diameter. The findings of the present study have important clinical implications with respect to performing coronary stent implantation with precision.

Despite improvements in catheter-based revascularization outcomes, coronary interventionalists face difficult challenges in the treatment of the thrombus-laden coronary lesion. In this report, we describe the use of the Acolysis device, which utilizes high-frequency (41.9 kHz) ultrasonic energy to vibrate a small metal tip at the end of a 4.5 Fr catheter to treat two thrombotically occluded saphenous vein grafts in two patients. In both cases, the Acolysis device provided normalization of flow with angiographically evident dissolution of thrombus and excellent acute angiographic and clinical results. We conclude that in these two selected cases the Acolysis device was used safely and effectively for thrombus debulking as an adjunct to stenting in diseased saphenous vein bypass grafts.

The efficacy of abciximab and moderate dose heparin in attaining reperfusion in acute MI was tested in a multicenter pilot study. Patients with acute MI of less than 6-hr onset triaged to primary PTCA received intravenous abciximab bolus and infusion and heparin (70 u/kg) in the emergency room. Mean time to angiography from administration of abciximab was 34 +/- 23 min. TIMI flow rates were: grade 0-62%, grade I-20%, grade II-9%, and grade III-9%. Primary PTCA was performed with 100% success rate. Access site bleeding occurred in 10% of patients with no incidence of intracranial bleeding. TIMI II/III flow rates were 50% in a patient subset where angiography was delayed by 45 min. While not an alternative to thrombolytics in AMI, abciximab administration in the emergency room in patients triaged to PTCA may be beneficial in situation where door to needle time is delayed as TIMI II/III flows may be attained in some patients. Cathet. Cardiovasc. Intervent. 48:430-434, 1999.

Slow or no reflow is a serious problem complicating catheter-based revascularization of degenerated saphenous vein bypass grafts. We examined the efficacy of rapidly delivered, high-velocity injections of intracoronary adenosine to reverse 11 slow-flow events complicating stenting of diseased bypass grafts. Ten of 11 events were rapidly improved to TIMI 3 flow by this technique within 3.8+/-1.6 min of the initial adenosine injection. In an ex vivo model, 3-ml syringes created higher peak pressures and velocities than 10- and 20-ml syringes. We conclude that rapid and repeated high-velocity intragraft administration of adenosine is a promising new approach to promptly reverse no-reflow events complicating PTCA and stenting of diseased saphenous vein grafts. Ex vivo studies demonstrate a potentially important mechanical advantage with the use of small syringes for injection. Further randomized studies will be required to better define the mechanism(s) and efficacy of this approach for treating no reflow, including its use in native vessels.

Rupture of an atherosclerotic coronary arterial plaque, as occurs spontaneously in patients with acute coronary syndromes, or as the result of a percutaneous coronary intervention (PCI), may serve as a stimulus for platelet adhesion, aggregation, and thrombus formation. Resultant platelet-mediated thromboembolic events are believed to cause a large percentage of the non–q-wave myocardial infarctions (MIs), and a rare need for early (b24 hours) repeat target lesion revascularization after PCI. A number of trials have demonstrated the potential importance of glycoprotein (GP) IIb/IIIa inhibition as a means to reduce the incidence of periprocedural death, myocardial infarction, and target lesion revascularization (MACE) during coronary angioplasty and stenting. 6 Thus, there is a rationale, supported by a significant body of clinical trial data, demonstrating the benefits of GP IIb/ IIIa inhibitor use during coronary interventions. Despite these potential benefits, many interventional cardiologists and hospitals have resisted the routine use of these agents because of the relatively high drugrelated costs, concerns about a possible increase in bleeding complications, and skepticism related to a relatively modest absolute reduction of MACE, when compared with unfractionated heparin alone. 6 The article presented by Marmur et al in the current issue of the Journal suggests that we may be able to improve clinical outcomes, with properly directed and cost-effective use of powerful pharmacologic agents in the cardiac catheterization laboratory. The analysis presented by his group from the original EPIC Trial suggests that there may be significant clinical benefit to a simplified, bbolus-onlyQ regimen of a GP IIb/IIIa receptor blockade, even in relatively high-risk patients. As pointed out in the article by Marmur et al, there are several caveats to their observations. The EPIC Trial was

We report the use of a novel endovascular approach using chemical neurolysis, via periadventitial injection of dehydrated ethanol (EtOH) to perform renal artery denervation.A novel, three-needle delivery device was introduced into the renal arteries of adult swine using fluoroscopic guidance. EtOH was injected bilaterally with one injection per artery, via the three needles into the adventitial and periadventitial space, using EtOH doses 0.15 ml/artery; n=3, 0.30 ml/artery; n=3, and 0.60 ml/artery; n=3, with saline injection as a sham control (0.4 ml/artery; n=3), and naive subjects (n=7) as a true negative control. The renal parenchymal norepinephrine (NE) concentration at two-week follow-up was the primary efficacy endpoint. The mean renal NE reduction was 54%, 78% and 88% at doses of 0.15 ml, 0.30 ml and 0.60 ml, respectively (p0.0001 vs. controls). Histological examination revealed marked, and deep, circumferential renal nerve injury at depths of 2-8 mm from the intimal surface. There was no evidence of device-related or EtOH-induced injury to the intimal layers. In some samples at the higher EtOH doses, there was focal loss of smooth muscle cells in the outer media. Angiography at 45 days demonstrated normal appearing renal arteries with no detectable stenoses (n=8).Circumferential adventitial delivery of very low doses of EtOH may be a promising alternative to energy-based systems to achieve dose-dependent, and predictable renal denervation. Further study is warranted.

Background Neointimal formation causes restenosis after intracoronary stent placement. Endovascular radiation delivered via a stent has been shown to reduce neointimal formation after placement in porcine and rabbit iliac arteries. The objective of this study was to evaluate the dose-related effects of a β-particle–emitting radioactive stent in a porcine coronary restenosis model. Methods and Results Thirty-seven swine underwent placement of 35 nonradioactive and 39 β-particle–emitting stents with activity levels of 23.0, 14.0, 6.0, 3.0, 1.0, 0.5, and 0.15 μCi of 32 P. Treatment effect was assessed by histological analysis 28 days after stent placement. Neointimal and medial smooth muscle cell density were inversely related to increasing stent activity. The neointima of the high-activity (3.0- to 23.0-μCi) stents consisted of fibrin, erythrocytes, occasional inflammatory cells, and smooth muscle cells with partial endothelialization of the luminal surface. In the 1.0-μCi stents, the neointima was expanded and consisted of smooth muscle cells and a proteoglycan-rich matrix. The neointima of the low-activity (0.15- and 0.5-μCi) stents was composed of smooth muscle cells and matrix with complete endothelialization of the luminal surface. At low and high stent activities, there was a reduction in neointimal area (low, 1.63±0.67 mm 2 and high, 1.73±0.97 mm 2 versus control, 2.40±0.87 mm 2 ) and percent area stenosis (low, 26±7% and high, 26±12%) compared with control stents (37±12%, P ≤.01). The 1.0-μCi stents, however, had greater neointimal formation (4.67±1.50 mm 2 ) and more luminal narrowing (64±16%) than the control stents ( P Conclusions The differential response to the doses of continuous β-particle irradiation used in this experimental model suggests a complex biological interaction of endovascular radiation and vascular repair after stent placement. Further study is required to determine the clinical potential for this therapy to prevent stent restenosis.

We report initial successful results using a novel retrograde cutting (pullback) atherectomy catheter (PAC) to treat complex bifurcation coronary artery disease, in 2 patients. In one case a bifurcation lesion involving the left anterior descending and a large diagonal branch was treated without the need for two-wire or kissing-balloon technique. In the second case a high-grade eccentric lesion of the right coronary artery at the site of a right ventricular marginal branch was treated successfully. This report describes the first clinical application of pullback atherectomy in human coronary circulation, and suggests that this device may play a useful role in the treatment of complex bifurcation coronary artery disease. © 1996 Wiley-Liss, Inc.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute ischaemic coronary events. It usually occurs during pregnancy or in the post-partum period in young women who have no traditional risk factors for coronary artery disease. We present two cases of SCAD in post-partum young women, who presented acutely with chest pain. Both underwent coronary angiography after worsening cardiac biomarkers. We utilised intravascular ultrasound (IVUS) in the first case, and optical coherence tomography (OCT) in the second case in order to confirm the diagnosis, define the anatomy and to measure the lesion length. This also serves to review the current literature and the available guidelines for treatment options for SCAD. We conclude that it is important to suspect SCAD as a cause of acute coronary syndrome in young female patients who present with chest pain especially in the post-partum period. These case studies also suggest a valuable role for IVUS and/or OCT in suspected cases of SCAD. This imaging is helpful in confirmation of the diagnosis, and allows optimal and precise treatment.

BACKGROUND Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by medial and/or intimal smooth muscle cell (SMC) proliferation. The objective of this study was investigate the ability of local emission of beta-particles from a 32P-impregnated titanium "stent" wire source to inhibit vascular SMC and endothelial cell proliferation in cell culture and to determine the dose-response characteristics of this inhibition. METHODS AND RESULTS A series of experiments were performed using 0.20-mm-diameter titanium wires that were impregnated with varying low concentrations of 32P (activity range, 0.002 to 0.06 microCi/cm wire, n = 47) or 31P (nonradioactive control, n = 28) in cultures of rat and human aortic SMCs and in cultured bovine aortic endothelial cells. The zone of complete cell growth inhibition (in millimeters from stent wire) was measured using light microscopy in the cultures exposed to the radioactive (32P) or control (31P) wires at 6 and 12 days after plating. In both rat and human SMC cultures there was a distinct 5.5- to 10.6-mm zone of complete SMC inhibition at wire activity levels > or = 0.006 microCi/cm. In contrast, there was no zone of inhibition surrounding the control (31P impregnated) wires (P < .001 versus 32P wires at all wire activities > or = 0.006 microCi/cm for human and rat SMCs). Proliferating bovine endothelial cells were more radioresistant than SMCs, with no zone of inhibition observed at wire activity levels up to 0.019 microCi/cm (P < .001 versus SMCs at 0.006 microCi/cm and 0.019 microCi/cm). CONCLUSIONS We conclude that very low doses of beta-particle emission from a 32P-impregnated stent wire (activity levels as low as 0.006 microCi/cm of wire) completely inhibit the growth and migration of both rat and human SMCs within a range of 5.5 to 10.6 mm from the wire. Endothelial cells appear to be much more radioresistant than SMCs. These data suggest that an intra-arterial stent impregnated with a low concentration of 32P may have a salutary effect on the restenosis process. Whether this approach can be used successfully and safely to inhibit restenosis in vivo and in the clinical setting is under investigation.