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Background: Transcatheter aortic valve replacement is an established treatment option for patients with severe symptomatic aortic stenosis and is most commonly performed through the transfemoral access route. Percutaneous access site closure can be achieved using dedicated plug-based or suture-based vascular closure device (VCD) strategies, but randomized comparative studies are scarce. Methods: The CHOICE-CLOSURE trial (Randomized Comparison of Catheter-based Strategies for Interventional Access Site Closure during Transfemoral Transcatheter Aortic Valve Implantation) is an investigator-initiated, multicenter study, in which patients undergoing transfemoral transcatheter aortic valve replacement were randomly assigned to vascular access site closure using either a pure plug-based technique (MANTA, Teleflex) with no additional VCDs or a primary suture-based technique (ProGlide, Abbott Vascular) potentially complemented by a small plug. The primary end point consisted of access site– or access-related major and minor vascular complications during index hospitalization, defined according to the Valve Academic Research Consortium-2 criteria. Secondary end points included the rate of access site– or access-related bleeding, VCD failure, and time to hemostasis. Results: A total of 516 patients were included and randomly assigned. The mean age of the study population was 80.5±6.1 years, 55.4% were male, 7.6% of patients had peripheral vascular disease, and the mean Society of Thoracic Surgeons score was 4.1±2.9%. The primary end point occurred in 19.4% (50/258) of the pure plug-based group and 12.0% (31/258) of the primary suture-based group (relative risk, 1.61 [95% CI, 1.07–2.44], P =0.029). Access site– or access-related bleeding occurred in 11.6% versus 7.4% (relative risk, 1.58 [95%CI: 0.91–2.73], P =0.133) and device failure in 4.7% versus 5.4% (relative risk, 0.86, [95% CI, 0.40–1.82], P =0.841) in the respective groups. Time to hemostasis was significantly shorter in the pure plug-based group (80 [32–180] versus 240 [174–316] seconds, P Conclusions: Among patients treated with transfemoral transcatheter aortic valve replacement, a pure plug-based vascular closure technique using the MANTA VCD is associated with a higher rate of access site– or access-related vascular complications but a shorter time to hemostasis compared with a primary suture-based technique using the ProGlide VCD. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04459208.

BACKGROUND There were gaps between guidelines and practice when surgery was the only treatment for aortic stenosis (AS). OBJECTIVES This study analyzed the decision to intervene in patients with severe AS in the EORP VHD (EURObservational Research Programme Valvular Heart Disease) II survey. METHODS Among 2,152 patients with severe AS, 1,271 patients with high-gradient AS who were symptomatic fulfilled a Class I recommendation for intervention according to the 2012 European Society of Cardiology guidelines; the primary end point was the decision for intervention. RESULTS A decision not to intervene was taken in 262 patients (20.6%). In multivariate analysis, the decision not to intervene was associated with older age (odds ratio [OR]: 1.34 per 10-year increase; 95% CI: 1.11 to 1.61; P = 0.002), New York Heart Association functional classes I and II versus III (OR: 1.63; 95% CI: 1.16 to 2.30; P = 0.005), higher age adjusted Charlson comorbidity index (OR: 1.09 per 1-point increase; 95% CI: 1.01 to 1.17; P = 0.03), and a lower transaortic mean gradient (OR: 0.81 per 10-mm Hg decrease; 95% CI: 0.71 to 0.92; P < 0.001). During the study period, 346 patients (40.2%, median age 84 years, median EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 3.1%) underwent transcatheter intervention and 515 (59.8%, median age 69 years, median EuroSCORE II 1.5%) underwent surgery. A decision not to intervene versus intervention was associated with lower 6-month survival (87.4%; 95% CI: 82.0 to 91.3 vs 94.6%; 95% CI: 92.8 to 95.9; P < 0.001). CONCLUSIONS A decision not to intervene was taken in 1 in 5 patients with severe symptomatic AS despite a Class I recommendation for intervention and the decision was particularly associated with older age and combined comorbidities. Transcatheter intervention was extensively used in octogenarians. (J Am Coll Cardiol 2021;78:2131-2143) (c) 2021 by the American College of Cardiology Foundation.

BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.FUNDING: Bayer AG.

Transradial access (TRA) has become a standard approach for cardiac catheterization. However, an obstacle to TRA is the risk of radial artery occlusion (RAO) after radial access in about 5%-10% of patients. We analyzed the safety and efficacy of getting vascular access after RAO by percutaneous transluminal angioplasty in cases of chronic radial occlusion.Chronic RAO was confirmed by Allen test and color Doppler in 8 patients. TRA was achieved by puncture in the distal tabatiere (anatomical snuffbox) using Seldinger's technique followed by insertion of a 5 Fr radial introducer sheath. Angiogram was obtained before percutaneous transluminal angioplasty with a 2.0 mm coronary balloon to reopen the artery. Puncture of the occluded radial artery, percutaneous transluminal angioplasty, and subsequent coronary catheterization and PCI were successful in all 8 patients. One complication was a dissection of the radial artery without further adverse events. No hemorrhage or compartment syndrome occurred.With increased application of TRA, the incidence of RAO is also rising. Some patients with RAO require repeat cardiac catheterization. Given the risk of damaging the contralateral radial artery in subsequent procedures, using the same access site is desirable. We demonstrate that it is feasible to get access to an occluded radial artery by percutaneous transluminal angioplasty.

Background Previous studies have reported slightly higher stroke rates in Takotsubo Syndrome compared to acute myocardial infarction. Our goal was to evaluate the temporal course of stroke rates and left ventricular recovery in patients with Takotsubo Syndrome. Methods We retrospectively examined the clinical and imaging data of 72 patients with Takotsubo Syndrome. The data collected came from January 2005 to March 2017. Left ventricular performance was evaluated by cardiovascular magnetic resonance imaging (MRI) in all patients during the acute phase of Takotsubo Syndrome and in a follow-up scan 2 months later. Acute stroke and major adverse clinical events, such as myocardial infarction or recurrence of Takotsubo Syndrome and death, were also determined for each patient at 30 days and 12 months after initial presentation. Results The MRI scans performed during the acute phase of Takotsubo Syndrome demonstrated apical ballooning with anterior wall motion dysfunction in 65 (90%) patients. Imaging performed 2 months later demonstrated resolution of this in 97% of those patients. Median left ventricular ejection fraction also significantly increased between both scans (49.5% vs. 64.0%, P

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, pINTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.FUNDING: Bayer AG.

Aims No intraprocedural assessment is currently available to evaluate the extent of nerve ablation by renal denervation (RDN). We prospectively evaluated the association of intraprocedural reduction of renal veno-arterial norepinephrine gradient with blood pressure (BP) response after RDN. Methods and results In 46 consecutive RDN patients, the periprocedural norepinephrine veno-arterial difference was defined as veno-arterial norepinephrine gradient. We observed a reduction of the office systolic BP from 176±19 mmHg to 165±24 mmHg (p=0.02) at three months and 163±22 mmHg (p=0.02) at six months. The mean and maximum systolic ABP decreased by 5 mmHg (p=0.03) and 9 mmHg (p=0.02), respectively. There was a decrease of the norepinephrine RV-RA difference from pre- to post-procedural levels (median 186 pg/ml [54;466] vs. 81 pg/ml [0;182], p=0.02). OBP responders (office systolic BP reduction ≥10 mmHg) showed a greater reduction of the norepinephrine gradient compared to non-responders (-290±450 pg/ml vs. -4±106 pg/ml, p=0.01). Patients with a reduction of norepinephrine gradient in both kidneys showed the most pronounced decrease of the systolic OBP (-24±14 mmHg) compared to patients with a reduction of norepinephrine gradient in only one kidney (-7±15 mmHg) or patients without a norepinephrine reduction (-3±19 mmHg, p=0.03 vs. bilateral reduction). Conclusions Measuring renal norepinephrine gradient during RDN may be a method to gauge the extent of renal nerve ablation.

AIMS Transcatheter mitral valve repair has become a promising alternative treatment option for severe symptomatic mitral regurgitation in patients at high risk for open heart surgery with heart-lung bypass. METHODS AND RESULTS We describe the first successful procedure of mitral clipping through a right lateral mini-thoracotomy via the right upper pulmonary vein in a patient with an agenesis of the inferior vena cava. The set-up of the MitraClip system on a separate table located at 70i on the right side of the patient and the fixation of the steerable sheath at the entry into the thorax with constant posterior pressure enabled clip implantation using the usual manoeuvres with marked reduction of the mitral insufficiency. CONCLUSIONS The access through the right upper pulmonary vein using the usual right mini-thoracotomy enabled a successful mitral clipping even in the absence or occlusion of the inferior vena cava.

Background Medical devices such as implant delivery systems are commonly used during minimally invasive procedures in the cardiovascular system. These devices often have lubricious polymer coatings to reduce friction between the device and blood vessels but coatings may separate and potentially cause serious injuries to patients. Methods Lubricious coated eSheaths for transcatheter heart valve implantation were assessed for luminal integrity at the proximal, medial and distal part. We assessed the number, depths and area of luminal trails using environmental scanning electron microscope (ESEM), white light interferometry (WLI) and optical profilometry using area scale fractal complexity (asfc) as surface parameters. A total of 15 eSheaths were retrieved and analyzed after successful femoral transcatheter Sapien 3 implantation in patients (23 mm valve– 14F eSheath, 26 mm valve– 14F eSheath and 29 mm valve– 16F eSheath, n = 5 for each group). Unused eSheaths (14F and 16F) served as controls (n = 5 for each group). Results ESEM revealed significantly greater number of trails after TAVR passage with the 23 mm, 26 mm and 29 mm valves compared to unused control 14F and 16F eSheaths (13.9 ± 3.1, 14.2 ± 2.3, 15.8 ± 1.7 vs. 0.08 ± 0.1 and 1.0 ± 0.5 [n]; p ≤ 0.0001 for all comparisons). Similarly, WLI showed minor, but significantly greater areas of luminal defects after 23 mm, 26 mm and 29 mm valve implantation vs. 14F and 16F unused controls (7.5 ± 0.9, 10.3 ± 1.1, 10.4 ± 1.4 vs. 4.1 ± 0.4 and 2.2 ± 0.4 [μm2], p = 0.0081). Likewise, the 3D-surface-measurement showed comparable results after implantation of the 23 mm, 26 mm and 29 mm valves vs. 14F and 16F unused control eSheaths (79.5 ± 6.3, 105.9 ± 5.3, 98.8 ± 4.8 vs. 5.1 ± 2.8 and 5.6 ± 0.5 [asfc] p = 0.0001). Conclusion Measurable defects of the luminal layer occur during balloon expandable TAVR using 14F and 16F eSheaths though this is likely clinically insignificant. Further clinical investigations including a prospective assessment of minor peripheral embolization are needed to fully address the impact of this luminal defects. Published version

Aims We aimed to investigate a fully bioresorbable poly-l-lactide (PLLA) scaffold to assess vascular remodelling in comparison to a permanent polymeric metal DES. Methods and results Twenty-five New Zealand white rabbits received an Absorb bioresorbable vascular scaffold (BVS, 1.0 and 1.1) or a CYPHER sirolimus-eluting stent (SES) in the iliac arteries. Twelve arteries were harvested at one month for scanning electron microscopy (SEM) analysis (BVS 1.1). The other implanted (BVS 1.0) arteries (n=32) were explanted at three, six and 36 months for light microscopic analysis. Re-endothelialisation assessed at one month was incomplete in both BVS and SES by SEM, with a trend towards greater coverage in SES (endothelialisation above strut: 32.2% vs. 60.6%, p=0.10). However, light microscopic analysis at later time points revealed greater endothelial coverage in BVS than in SES at 36 months (100.0% vs. 93.3%, p=0.05). Inflammation scores were comparable between arteries implanted with BVS and SES at three months (1.1 vs. 1.1, p=0.99), which decreased over time in the BVS implanted arteries (36 months: 0.0 vs. 0.2, p=0.05). At 36 months, BVS were completely resorbed, and resorption sites were replaced by connective tissue. Conclusions BVS in the rabbit iliac artery model demonstrated ongoing vascular healing at three and six months, and complete vessel restoration, re-endothelialisation and no to minimal vascular inflammation at 36 months.

The mitral clipping technique is emerging as a promising new treatment option for severe mitral regurgitation. The device was designed and assessed in intermediate risk populations, which is in contrast to the real world, where most patients are deemed to be at very high risk for open heart surgery. The cardiac anatomy of these patients often challenges the freedom grades of the current mitral clip device. In this case presentation, we describe a novel technique overcoming extreme atrial dilation in a patient with severe mitral regurgitation despite previous implantation of two mitral clips. Based on a low/anterior trans-septal puncture, this procedure relied on a counter clock-wise 90° turn of the steerable sheath and alignment of the clip delivery system to the mitral valve, thereby gaining additional longitudinal freedom. This resulted in the successful implantation of two additional clips with achievement of a mild to moderate mitral regurgitation without relevant gradient and dramatic and sustained clinical improvement of the patient.

Coronary stenting represents the standard of care for percutaneous revascularization of symptomatic coronary artery disease. However, despite progress in the evolution of intravascular stents, clinical adverse events such as restenosis and stent thrombosis still represent the “achilles heel” of this ground-breaking technology. Of particular note was the association of these adverse events with the material, the polymer coating, and the active drug of currently approved drug eluting stents. Consequently, modifications were made to the design, coating, and the choice of drugs, eventually, resulting in (fully) biodegradable drug-eluting stents. Such stents offer the appealing concept of a temporary vascular scaffold and are currently under extensive preclinical and clinical investigation. However, biodegradable stents must demonstrate efficacy and safety in larger randomized clinical trials in real-world scenarios, which are currently on the horizon.

Background Despite the technical advancements of the transcatheter aortic valve implantation (TAVI) procedure, valve embolisation into the left ventricle remains a challenging situation requiring expedited management through the Heart Team. Investigation The advantages and pitfalls of an interventional transfemoral approach, a transapical extraction of the dislocated prosthesis or the conversion to open heart surgery have to be balanced depending on the overall situation and the specific characteristics of the patient. Diagnosis A transfemoral approach would be the first choice for most TAVI implanters. We discuss the different options and present an elegant solution solving this challenging situation, leading to a good immediate and long-term outcome. Management Attempts at pulling the prosthesis out of the ventricle using a balloon remained unsuccessful. After grasping of the prosthesis with a goose-neck snare, the valve was pulled into the annulus. A second SAPIEN XT prosthesis was implanted and fixed the first prosthesis within the annulus. After post-dilatation, there was a good result without relevant gradient and minimal aortic regurgitation.

To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques.All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen κ statistic.Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both P.0001), while mixed plaque at coronary CT angiography, calcified plaque at intravascular US, and lipid-rich plaque at OFDI were associated with advanced lesions (OR: 2.49, P=.0003; OR: 2.60, P=.002; and OR: 31.2, P.0001, respectively). OFDI had higher accuracy for discriminating early from advanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, P.0001). Interobserver agreement was excellent for OFDI and coronary CT angiography (κ=0.87 and 0.85, respectively) and was good for intravascular US (κ=0.66).Systematic and standardized comparison between invasive and noninvasive modalities for coronary plaque characterization in ex vivo specimens demonstrated that coronary CT angiography and intravascular US are reasonably associated with plaque composition and lesion grading according to histopathologic findings, while OFDI was strongly associated. These data may help to develop initial concepts of sequential imaging strategies to identify patients with advanced coronary plaques.

Objectives This study sought to examine the capability of optical frequency domain imaging (OFDI) to characterize various morphological and histological responses to stents implanted in human coronary arteries. Background A precise assessment of vascular responses to stents may help stratify the risk of future adverse events in patients who have been treated with coronary stents. Methods Fourteen human stented coronary segments with implant duration ≥1 month from 10 hearts acquired at autopsy were interrogated ex vivo by OFDI and intravascular ultrasound (IVUS). Comparison with histology was assessed in 134 pairs of images where the endpoints were to investigate: 1) accuracy of morphological measurements; 2) detection of uncovered struts; and 3) characterization of neointima. Results Although both OFDI and IVUS provided a good correlation of neointimal area with histology, the correlation of minimum neointimal thickness was inferior in IVUS (R2 = 0.39) as compared with OFDI (R2 = 0.67). Similarly, IVUS showed a weak correlation of the ratio of uncovered to total stent struts per section (RUTSS) (R2 = 0.24), whereas OFDI maintained superiority (R2 = 0.66). In a more detailed analysis by OFDI, identification of individual uncovered struts demonstrated a sensitivity of 77.9% and specificity of 96.4%. Other important morphological features such as fibrin accumulation, excessive inflammation (hypersensitivity), and in-stent atherosclerosis were characterized by OFDI; however, the similarly dark appearance of these tissues did not allow for direct visual discrimination. The quantitative analysis of OFDI signal reflections from various in-stent tissues demonstrated distinct features of organized thrombus and accumulation of foamy macrophages. Conclusions The results of the present study reinforce the potential of OFDI to detect vascular responses that may be important for the understanding of long-term stent performance, and indicate the capability of this technology to serve as a diagnostic indicator of clinical success.

Objectives This study sought to validate the sensitivity and specificity of the Academic Research Consortium's (ARC) classification of stent thrombosis. Background Classification of stent thrombosis according to ARC criteria has become widely accepted. The criteria have not been validated against an autopsy standard. Methods An autopsy registry of 139 subjects with prior coronary stenting underwent detailed histopathological analysis to assess for stent thrombosis. Based on clinical data only, cases were adjudicated according to ARC stent thrombosis criteria, including a proposed modification of the possible classification to include death beyond 30 days due only to sudden death or acute ischemia. Results Autopsy results confirmed 51 cases as positive and 88 as negative for stent thrombosis. Clinical adjudication classified 105 cases as definite (10), probable (31), or possible (64) ARC stent thrombosis. Specificity was high for definite (99%) and definite plus probable (83%) criteria, but sensitivity was poor at 18% and 51%, respectively. Including the possible cases improved sensitivity to 92% but reduced specificity to 34% (58 false positives). The modified possible criteria eliminated 13 false positive cases (specificity = 49%) and was the best approximation of a hypothetical gold standard in a sensitivity analysis if late death represented at least 20% of all stent thrombosis cases. Conclusions In a selected autopsy sample, restricting ARC stent thrombosis to definite or definite plus probable criteria results in substantial under-reporting of confirmed cases. Inclusion of a modified possible classification may provide the best estimate of late and very late stent thrombosis rates.

Objectives Human coronary bare-metal stents (BMS) and drug-eluting stents (DES) from autopsy cases with implant duration >30 days were examined for the presence of neointimal atherosclerotic disease. Background Neointimal atherosclerotic change (neoatherosclerosis) after BMS implantation is rarely reported and usually occurs beyond 5 years. The incidence of neoatherosclerosis after DES implantation has not been reported. Methods All available cases from the CVPath stent registry (n = 299 autopsies), which includes a total of 406 lesions—197 BMS, 209 DES (103 sirolimus-eluting stents [SES] and 106 paclitaxel-eluting stents [PES])—with implant duration >30 days were examined. Neoatherosclerosis was recognized as clusters of lipid-laden foamy macrophages within the neointima with or without necrotic core formation. Results The incidence of neoatherosclerosis was significantly greater in DES lesions (31%) than BMS lesions (16%; p Conclusions Neoatherosclerosis is a frequent finding in DES and occurs earlier than in BMS. Unstable features of neoatherosclerosis are identified for both BMS and DES with shorter implant durations for the latter. The development of neoatherosclerosis may be yet another rare contributing factor to late thrombotic events.

Objectives The purpose of this study was to assess the mechanism(s) of late stent thrombosis (LST) and vascular healing responses in first-generation polymeric drug-eluting stents (DES). Background Recent clinical trials have reported variations in late lumen loss between first-generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). Little is known, however, about the vascular responses, time course of healing, and underlying mechanism(s) of complications of LST between platforms in human coronary implants. Methods The overall analysis included 174 cases (230 DES lesions) from the CVPath Institute's stent registry. Histomorphometry was performed on coronary stents from 127 patients (171 lesions) who died ≥30 days after receiving stent implants in which fibrin deposition, endothelial strut coverage, inflammatory response, and mechanism(s) of in-stent thrombosis were assessed. Results Both platforms demonstrated increased neointimal thickness over time where values were greater in PES (mean 0.13 mm; range 0.03 to 0.20 mm) than SES (mean 0.10 mm; range 0.04 to 0.15 mm; p = 0.04). The percentage of uncovered struts was similar between SES and PES including stents with LST (SES = 21% vs. PES = 27%; p = 0.47). The underlying mechanism(s) of LST, however, was strikingly different between platforms; localized strut hypersensitivity was exclusive to SES, whereas malapposition secondary to excessive fibrin deposition was the underlying cause in PES. Moreover, although both PES and SES showed nearly complete strut coverage after 12 months for on-label use, the majority of stents placed for off-label indications remained unhealed after 12 months in both types of DES. Conclusions Differential mechanisms of LST involving either hypersensitivity or excessive fibrin were identified between first-generation DES in which overall stent healing was further delayed in DES placed for off-label indications.

First generation drug-eluting stents (DES) have significantly improved the treatment options for patients with symptomatic coronary artery disease by decreasing rates of acute vessel closure and restenosis after percutaneous coronary revascularization procedures. However, early enthusiasm was temperd by reports of late stent thrombosis (LST), which raised concerns about safety. Since millions of DES have been implanted in patients worldwide, it is imperative to understand the pathology of DES in man. Autopsy studies from the CVPath DES registry documented that delayed arterial healing is accompanied by poor endothelialization of stent struts which is the single best predictor of late stent thrombosis. Arterial healing of DES is highly heterogeneous and is dependent on underlying plaque morphology as well as on the stent location. We identified several anatomical and pathological changes in man, which were associated with LST; these include hypersensitivity reaction to polymer, plaque rupture, bifurcation sites, malapposition and stent fracture. DES was also associated with premature atherosclerotic changes versus BMS.

Background— We aimed to demonstrate that, by separating endothelial progenitor cell capture from sirolimus delivery through the application of drug to the abluminal surface of the stent, the degree of endothelialization can be enhanced. Methods and Results— Stainless steel R Stents, with biodegradable SynBiosys polymer coating with sirolimus abluminally applied and surface modified with anti-CD34 antibody were prepared at 2 dosages (low-dose sirolimus [LD-Combo, 2.5 μg sirolimus/mm] and full-dose sirolimus [Combo, 5 μg sirolimus/mm). These Combo stents and the Cypher stent (10 μg sirolimus/mm) were deployed in 98 normal porcine arteries and harvested for pharmacokinetic analysis at 0.25, 1, 3, 7, 14, 28, and 35 days. The LD-Combo stents showed faster early release (50%total dose in 72 hours) than the Combo and Cypher. At 30 days, drug release was near complete with both Combo stents, whereas 20% of drug remained on the Cypher stents. To assess efficacy, a total of 50 stents (Xience V=8, Cypher=8, Genous bioengineered R stent=6, LD-Combo=14, and Combo=14) were implanted in 18 pigs for 14 and 28 days. Optical coherence tomography was performed, and stents were harvested for histology. At 28 days, there was less neointimal thickness with Combo (0.173±0.088 mm) compared with Cypher (0.358±0.225 mm), LD-Combo (0.316±0.228 mm), and Xience V (0.305±0.252 mm; P Conclusions— Both optical coherence tomography and histology demonstrate that anti-CD34 sirolimus-eluting stents promote endothelialization while reducing neointimal formation and inflammation.

Objectives Using human pathologic specimens from the CVPath registry, we aimed to investigate the location of the atherosclerotic plaque at bifurcation in native coronary atherosclerotic lesions and to determine the responses at bifurcation after implantation of bare-metal stents (BMS) and drug-eluting stents (DES). Background Greater atherosclerotic plaque burden has been reported to occur at low-shear regions of bifurcation. Methods Twenty-six randomly selected human atherosclerotic nonstented coronary bifurcation lesions were examined longitudinally for plaque distribution in patients dying of severe coronary artery disease. Forty stented bifurcation lesions (21 BMS and 19 DES) were reviewed and analyzed by morphometry. Results In nonstented coronary bifurcations, the lateral wall showed significantly greater intima as well as necrotic core thickness than the flow divider. In the stented lesion, the frequency of late stent thrombosis was greater in the DES group (75%) than in the BMS group (36%), whereas restenosis was more frequent in the BMS group (33%) than in the DES group (5%). Neointimal formation was significantly less at the flow divider compared with the lateral wall in the DES group (0.07 mm [interquartile range (IQR) 0.03 to 0.15 mm] vs. 0.17 mm [IQR 0.09 to 0.23 mm]; p = 0.001), whereas this difference was not significant in the BMS group. Similarly, uncovered struts and fibrin deposition was significantly greater at the flow divider compared with the lateral wall in the DES group (uncovered: 40% [IQR 16% to 76%] vs. 0% [IQR 0% to 15%]; p = 0.001; fibrin: 60% [IQR 21% to 67%] vs. 17% [IQR 0% to 55%]; p = 0.01), but not in the BMS group. Conclusions Plaque formation in native coronary bifurcations and neointimal growth after DES implantation was significantly less at the flow divider versus the lateral wall. A higher prevalence of late stent thrombosis in DES compared with BMS was associated with greater uncovered struts at flow divider sites, which is likely due to flow disturbances.

The introduction of drug-eluting stents (DES) has significantly reduced restenosis when compared with bare-metal stents and are considered the standard of care in the treatment of symptomatic coronary artery disease. However, late stent thrombosis (LST), potentially resulting in a fatal occlusion of the vessel, emerged as a major concern in first-generation DES (polymer-based sirolimus- and paclitaxel-eluting stents). Pathologic studies of patients dying from late DES thrombosis showed that the underlying mechanism is delayed healing, characterized by poor endothelialization of stent struts and persistence of fibrin. Additional risk factors for LST include long lesions, left main coronary artery disease, bifurcation stenting, underlying ruptured plaques and hypersensitivity reactions. Most recently, correlation of intravascular ultrasound findings with histopathological analysis of thrombus aspirates in patients with very late DES thrombosis showed eosinophilic infiltrates were associated with intravascul...

Objectives The aim of this study was to perform pathologic assessment on stent fracture. Background Clinically, stent fracture has been reported in 1% to 2% of patients after drug-eluting stent (DES) implantation. Methods High-contrast film-based radiographs of 177 consecutive lesions from the CVPath DES autopsy registry were reviewed. Stent fracture was graded as I (single-strut fracture), II (≥2 struts), III (≥2 struts with deformation), IV (with transection without gap), and V (with transection causing gap in stent segment). The incidence of adverse pathologic findings (thrombosis and restenosis) was assessed histologically. Results Stent fracture was documented in 51 lesions (29%; grade I = 10, II = 14, III = 12, IV = 6, and V = 9). Lesions with stent fracture had longer duration after implantation (172 days [interquartile range (IQR) 31 to 630 days] vs. 44 days [IQR 7 to 270 days], p = 0.004), a higher rate of Cypher (Cordis Corp., Miami Lakes, Florida) stent usage (63% vs. 36%, p = 0.001), longer stent length (30.0 mm [IQR 22.0 to 40.0 mm] vs. 20.0 mm [IQR 14.0 to 27.3 mm], p Conclusions The incidence of stent fracture was 29% lesions at autopsy, which is much higher than clinically reported. A high rate of adverse pathologic findings was observed in lesions with grade V stent fracture, whereas fracture with grade I to IV did not have a significant impact on the pathological outcome.

Background— No clinical trial has yet focused on contrast-mediated nephrotoxicity in patients with chronic renal failure exclusively undergoing percutaneous coronary intervention (PCI). Therefore, the aim of this study was to compare the effect of contemporary contrast media on nephrotoxicity in this high-risk patient population. Methods and Results— This prospective, randomized, double-blind, comparative clinical trial randomly selected 939 patients with chronic renal failure undergoing coronary angiography with potential PCI to receive either the iso-osmolar contrast medium iodixanol or the low-osmolar contrast medium iomeprol. Of those 939 patients, 615 received diagnostic angiography only and were not included in the primary study analysis, but were followed up in a registry. Three hundred twenty-four patients underwent PCI, of which one-half received iodixanol or iomeprol, respectively, and were included in the primary study analysis. The primary end point was the peak increase in S -creatinine during hospitalization for PCI. Maximum increase in S -creatinine after PCI was lower than expected and thus impaired the power of the study. It was not significantly different between the 2 contrast groups (0.19�0.40 mg/dL for iodixanol and 0.21�0.34 mg/dL for iomeprol; P =0.53). Albeit contrast media-induced nephropathy rates were lower with iodixanol (22.2% compared with 27.8% for iomeprol), this difference was not statistically different ( P =0.25). Subgroup analysis suggested a favorable outcome regarding nephrotoxicity in patients who received higher contrast volumes (>340 mL) in the iodixanol group ( P interaction =0.016). Conclusions— Routine use of iso-osmolar contrast medium is not associated with a significant reduction of nephrotoxicity compared with low-osmolar contrast medium in patients with chronic renal failure undergoing PCI. However, a positive effect was seen in the iso-osmolar contrast group for patients receiving high amounts of contrast medium, which awaits confirmation of a specifically designed randomized clinical trial. Clinical Trial Registration— clinicaltrials.gov Identifier: NCT00390585

Despite advances in the pharmacotherapy of atherosclerosis, the most successful agents used to treat this disease - statins - remain ineffective for the primary or secondary prevention of myocardial infarction in about two-thirds of patients. The lack of a more robust treatment effect underscores the limitations of lipid lowering alone and emphasizes the complexity of the disease and the need for targeting other critical processes. Further, despite the rapid progress in newer imaging modalities, the inability adequately to characterize lesions in individual patients beyond simple angiographic terms presents another problem. We need to be able to understand in living patients the histologic characteristics of non-flow limiting lesions and how these relate to risk for future events. Moreover, we also need to be able to modify critical elements within the atherosclerotic plaque, specifically macrophage foam cells, neoangiogenesis, necrotic core size, and fibrous cap thickness. These advancements will require newer pharmacologic agents and clinical refinements in the monitoring of treatment effects.

Percutaneous coronary intervention with intracoronary stenting is the most widely performed procedure for the treatment of symptomatic coronary disease ([1][1]). Although drug-eluting stents (DES) have minimized the major limitation of bare-metal stents (BMS), i.e., restenosis, stent thrombosis has

All four currently FDA-approved drug-eluting stents (DESs) contain a durable polymeric coating which can negatively impact vascular healing processes and eventually lead to adverse cardiac events. Aim of this study was the pre-clinical assessment of two novel rapamycin-eluting stent (RES) coating technologies that abstain from use of a durable polymer. Two distinctive RES coating technologies were evaluated in vitro and in the porcine coronary artery stent model. The R-poly(S) stent platform elutes rapamycin from a biodegradable polymer that is top coated with the resin shellac to minimize the amount of polymer. The R-pro(S) stent platform allows dual drug release of rapamycin and probucol, blended by shellac. HPLC-based determination of pharmacokinetics indicated drug release for more than 28 days. At 30 days, neointimal formation was found to be significantly decreased for both DESs compared to bare-metal stents. Assessment of vascular healing revealed absence of increased inflammation in both DESs, which is commonly observed in DES with non-erodible polymeric coating. In conclusion, the pre-clinical assessment of RESs with resin-based or dual drug coating indicated an adequate efficacy profile as well as a beneficial effect for vascular healing processes. These results encourage the transfer of these technologies to clinical evaluation.

Current guidelines favor the radial approach for coronary angiography. Therefore, specialty radial diagnostic catheters were designed to engage both coronary arteries with a single device. However, it is unclear if single catheters are superior to conventional catheters. A retrospective analysis was performed of consecutive right radial coronary angiographies to determine catheter use, fluoroscopy time, radiation dosage, and consumption of contrast. Procedures were performed with a single TIG catheter or conventional catheters (CONV). Procedures with coronary artery bypass grafts or ventricular angiographies were excluded. 273 transradial procedures were performed successfully. 95 procedures were performed with CONV and 178 procedures with a TIG. Crossover to additional catheters was higher in TIG (15.2%) compared to CONV (5.3%,p=0.02). Fluoroscopy time was comparable between CONV and TIG, without crossover (2.2±1.2 min versus2.3±1.2 min; n.s.), however, greater in the case of crossover for CONV (5.8±0.7) and TIG (7.6±3.0;p=0.0001). Radiation dosage was similar in CONV and the TIG, without crossover (1419±1075, cGy∗cm2versus1690±1138; n.s.), however, greater for CONV (2374±620) and TIG (3733±2281,p=0.05) with crossover. Overall, the amount of contrast was greater in TIG (56±13 mL) versus CONV (48±3 mL;p=0.0003). CONV femoral catheters may be the primary choice for radial approach.

Innovative catheter systems with lower-profile sheaths and a dynamic expansion mechanism (DEM) were recently introduced for transcatheter aortic valve replacement (TAVR). However, the labeling of 14 F and 16 F eSheaths denote the inner nominal diameter. Exact changes of the clinically relevant outer diameters during usage are not available. eSheaths were measured every 30 mm using a digital caliper. Unused 14 F and 16 F eSheaths served as controls. Maximum eSheath diameters were measured after insertion of the Edwards Commander Delivery System (ECDS) into 14 F and 16 F eSheaths.Finally, eSheaths were retrieved and measured after TAVR. Outer diameters of control 14 F eSheaths were 5.8 mm and 6.50 mm for the 16 F eSheath. Introduction of the 23 mm and 26 mm ECDS into 14 F eSheaths showed a maximum diameter of 7.65 mm and 7.64 mm (P=NS). Introduction of the 29 mm ECDS into the 16 F eSheath showed the greatest diameter of 8.18 mm (P=0.03). After TAVR, diameters of the 14 F eSheaths were 7.14 mm (23 mm valve) and 7.26 mm (26 mm valve) (P=NS), while 16 F eSheaths were 8.10 mm (29 mm valve) (P≤0.03). Nominal 14 F and 16 F eSheaths showed a significant increase of the outer diameter during advancement of the ECDS and after TAVR implantation.

Background—Enteroviridae such as coxsackievirus B3 (CVB3) are important infectious agents involved in viral heart disease, hepatitis, and pancreatitis, but no specific antiviral therapy is available.Methods and Results—The aim of the present study was to evaluate the impact of RNA interference on viral replication, cytopathogenicity, and survival. Small interfering RNA (siRNA) molecules were designed against the viral 2A region (siRNA-2A), which is considered to be highly conserved and essential for both virus maturation and host cytopathogenicity. siRNA-2A exhibited a significant protective effect on cell viability mediated by marked inhibition of CVB3 gene expression and viral replication. In highly susceptible type I interferon receptor–knockout mice, siRNA-2A led to significant reduction of viral tissue titers, attenuated tissue damage, and prolonged survival. Repeated siRNA-2A transfection was associated with a further improvement of survival. Various control siRNA molecules had no protective effect in vitro or in vivo.Conclusions—RNA interference directed against the 2A protease encoding genomic region effectively confers intracellular immunity toward CVB3-mediated cell injury and improves survival, suggesting a potential role for RNA interference for future treatment options targeting enteroviral diseases.

Despite prompt revascularization, some patients with acute myocardial infarction (AMI) develop myocardial scars, which can be visualized by late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR). Our goal was to identify angiographic findings that were predictive for scar development in patients after reperfused AMI. We examined 136 patients after first ST-elevated myocardial infarction by CMR after a median of 4 days (range: 2–7). Patients with manifestation of LGE were matched to patients without LGE by means of age and gender. Clinical follow-up with a combined primary endpoint including myocardial reinfarction, congestive heart failure, stroke, death and development of left ventricular thrombus was reported after 24 months. Patients with manifestation of LGE had a significant longer time of symptom-to-intervention, a higher prevalence of anterior AMI, and more proximal culprit lesions. Furthermore, left ventricular ejection fraction was significantly decreased, and peak values of infarct markers were significantly higher in these patients. Preinterventional thrombolysis in myocardial infarction-0-flow was significantly more frequent in patients with LGE manifestation. The presence of 3-vessel disease (odds ratio 53.99, 95% confidence interval 8.22–354.63, P

The precise sequence of events leading to carotid plaque vulnerability is as yet unknown, and the majority of ischemic strokes seem to result from atherosclerotic plaque rupture or thrombus propagation at the carotid bifurcation.1 Traditionally, the surgical approach of carotid endarterectomy is well accepted for the treatment of symptomatic and severe asymptomatic carotid stenosis.2,3 More recently, carotid artery stenting has arisen as the preferred, less invasive technique for the treatment of symptomatic and asymptomatic severe stenosis in patients with anatomically or physiologically high-risk features.4,5 To date, the mechanisms of recurrent stroke after carotid artery stenting have not been well characterized. A 79-year-old woman with a history of recurrent left hemispheric strokes underwent surgical resection of her left carotid artery 3 years after its stenting. The patient initially presented with recurrent ischemia after a left hemispheric stroke. Carotid ultrasound revealed a severe unilateral left internal carotid stenosis (peak systolic velocities were measured to be 408 cm/s with an internal carotid artery/common carotid artery ratio of 8.87). The patient was enrolled in the Carotid Revascularization Endarterectomy versus Stent Trial and randomized to receive a stent.6 A tapered 8 mm to 6 mm×40 mm open cell self-expanding stent (Acculink, Abbott Vascular, Abbott …

Background— Clinical trials have demonstrated that the second-generation cobalt-chromium everolimus-eluting stent (CoCr-EES) is superior to the first-generation paclitaxel-eluting stent (PES) and is noninferior or superior to the sirolimus-eluting stent (SES) in terms of safety and efficacy. It remains unclear whether vascular responses to CoCr-EES are different from those to SES and PES because the pathology of CoCr-EES has not been described in humans. Methods and Results— A total of 204 lesions (SES=73; PES=85; CoCr-EES=46) from 149 autopsy cases with duration of implantation >30 days and ≤3 years were pathologically analyzed, and comparison of vascular responses was corrected for duration of implantation. The observed frequency of late and very late stent thrombosis was less in CoCr-EES (4%) versus SES (21%; P =0.029) and PES (26%; P =0.008). Neointimal thickness was comparable among the groups, whereas the percentage of uncovered struts was strikingly lower in CoCr-EES (median=2.6%) versus SES (18.0%; P P P =0.007 for CoCr-EES versus SES), whereas fracture-related restenosis or thrombosis was comparable among the groups (CoCr-EES=6.5%; SES=5.5%; PES=1.2%). Conclusions— CoCr-EES demonstrated greater strut coverage with less inflammation, less fibrin deposition, and less late and very late stent thrombosis compared with SES and PES in human autopsy analysis. Nevertheless, the observed frequencies of neoatherosclerosis and fracture-related adverse pathological events were comparable in these devices, indicating that careful long-term follow-up remains important even after CoCr-EES placement.

This study was designed to evaluate the pharmacokinetic and vascular healing of a second-generation everolimus-eluting stent (EES) and slow-release zotarolimus-eluting stent (R-ZES).Second-generation DESs have alleviated the safety concerns of late stent thrombosis by addressing issues of polymer biocompatibility and stent design, and optimizing drug loads and release kinetics. No preclinical comparison study exists between these stents.Rabbit iliac artery stent implantation was performed using Xience Prime EES and Resolute R-ZES. Histomorphometric evaluation was performed at 28 and 60 days after implantation in an induced atheroma model. Endothelial coverage and maturation were assessed by scanning electron microscopy and immuno-labeling at 14 and 28 days following deployment. For pharmacokinetic studies, arterial tissue and stents were retrieved at 3, 14, 28, and 90 days, and blood samples were obtained during the first 24 hours.Vascular remodeling (percent stenosis, neointimal thickness) was similar in arteries implanted with either stent group. At 28 days, inflammation was significantly less in the EES group as compared to the R-ZES group (inflammation score: 1.59 ± 0.52 vs 2.22 ± 0.69, respectively; P=.044), with no differences observed at 60 days. Endothelial coverage was similar between both groups; however, endothelial maturation above stent struts was significantly higher in the EES group vs R-ZES group at 28 days (33 ± 20% vs 22 ± 21%, respectively; P=.040). Arterial drug level concentrations were also shown to be significantly less in the EES group vs the R-ZES group (P.0001).Overall, EES and R-ZES displayed similar remodeling properties with lower arterial drug levels observed in the EES group vs the R-ZES group, which may have led to more rapid endothelial maturation.

The mitral clipping technique is emerging as a promising new treatment option for severe mitral regurgitation. The device was designed and assessed in intermediate risk populations, which is in contrast to the real world, where most patients are deemed to be at very high risk for open heart surgery. The cardiac anatomy of these patients often challenges the freedom grades of the current mitral clip device. In this case presentation, we describe a novel technique overcoming extreme atrial dilation in a patient with severe mitral regurgitation despite previous implantation of two mitral clips. Based on a low/anterior trans-septal puncture, this procedure relied on a counter clock-wise 90° turn of the steerable sheath and alignment of the clip delivery system to the mitral valve, thereby gaining additional longitudinal freedom. This resulted in the successful implantation of two additional clips with achievement of a mild to moderate mitral regurgitation without relevant gradient and dramatic and sustained clinical improvement of the patient.

ObjectivesThis study sought to evaluate the impact of anatomic and procedural variables on the outcome of the unprotected left main coronary artery (uLMCA) itself after drug-eluting stent (DES) implantation.BackgroundThere is a controversial debate regarding when and how to perform percutaneous coronary intervention (PCI) for an uLMCA stenosis.MethodsThis analysis is based on a randomized study of 607 patients undergoing PCI for uLMCA, randomized 1:1 to receive paclitaxel- or sirolimus-eluting stents. We evaluated the impact of the SYNTAX score, uLMCA anatomy, and stenting technique on in-stent restenosis (ISR), target lesion revascularization (TLR), and the 3-year outcomes.ResultsThe 3-year cardiac mortality rate was 5.8%; 235 (39%) patients had a true bifurcation lesion (TBL), and the median SYNTAX score was 27. TBL was associated with a higher need for multiple stents (72% vs. 37%, p < 0.001). TBL was a significant predictor of ISR (23% vs. 14%, p = 0.008) and for TLR (18% vs. 9%, p < 0.001). The need for multiple stents was a predictor of ISR (22% vs. 13%, p = 0.005) and for TLR (16% vs. 9%, p = 0.005). Culotte stenting showed better results compared with T-stenting for ISR (21% vs. 56%, p = 0.02) and for TLR (15% vs. 56%, p < 0.001). We observed a significant association between uLMCA-TLR and SYNTAX scores (9.2% for scores ≤22, 14.9% for scores 23 to 32, and 13.0% for scores ≥33, p = 0.008).ConclusionsPCI of uLMCA lesions with DES is safe and effective out to 3 years. TBL and multiple stents were independent predictors for ISR. In the multivariate analysis, independent predictors for TLR were TBL, age, and EuroSCORE (European System for Cardiac Operative Risk Evaluation). (Drug-Eluting-Stents for Unprotected Left Main Stem Disease [ISAR-LEFT-MAIN]; NCT00133237)

In coronary computed tomographic angiography (CTA), low attenuation of coronary atherosclerotic plaque is associated with lipid-rich plaques. However, an overlap in Hounsfield units (HU) between fibrous and lipid-rich plaque as well as an influence of luminal enhancement on plaque attenuation was observed and may limit accurate detection of lipid-rich plaques by CTA. We sought to determine whether the quantitative histogram analysis improves accuracy of the detection of lipid-core plaque (LCP) in ex vivo hearts by validation against histological analysis.Human donor hearts were imaged with a 64-slice computed tomographic scanner using a standard coronary CTA protocol, optical coherence tomography (OCT), a histological analysis. Lipid-core plaque was defined in the histological analysis as any fibroatheroma with a lipid/necrotic core diameter of greater than 200 μm and a circumference greater than 60 degrees as well as a cap thickness of less than 450 μm. In OCT, lipid-rich plaque was determined as a signal-poor region with diffuse borders in 2 quadrants or more. In CTA, the boundaries of the noncalcified plaque were manually traced. The absolute and relative areas of low attenuation plaque based on pixels with less than 30, less than 60, and less than 90 HU were calculated using quantitative histogram analysis.From 5 hearts, a total of 446 cross sections were coregistered between CTA and the histological analysis. Overall, 55 LCPs (12%) were identified by the histological analysis. In CTA, the absolute and relative areas of low attenuation plaque less than 30, less than 60, and less than 90 HU were 0.14 (0.31) mm2 (4.22% [9.02%]), 0.69 (0.95) mm2 (18.28% [21.22%]), and 1.35 (1.54) mm2 (35.65% [32.07%]), respectively. The low attenuation plaque area correlated significantly with histological lipid content (lipid/necrotic core size [in square millimeter] and a portion of lipid/necrotic core on the entire plaque) at all thresholds but was the strongest at less than 60 HU (r = 0.53 and r = 0.48 for the absolute and relative areas, respectively). Using a threshold of 1.0 mm2 or greater, the absolute plaque area of less than 60 HU in CTA yielded 69% sensitivity and 80% specificity to detect LCP, whereas sensitivity and specificity were 73% and 71% for using 25.0% or higher relative area less than 60 HU. The discriminatory ability of CTA for LCP was similar between the absolute and relative areas (the area under the curve, 0.744 versus 0.722; P = 0.37). Notably, the association of the low attenuation plaque area in CTA with LCP was not altered by the luminal enhancement for the relative (P = 0.48) but for the absolute measurement (P = 0.03). Similar results were achieved when validated against lipid-rich plaque by OCT in a subset of 285 cross sections.In ex vivo conditions, the relative area of coronary atherosclerotic plaque less than 60 HU in CTA as derived from quantitative histogram analysis has good accuracy to detect LCP as compared with a histological analysis independent of differences in luminal contrast enhancement.

Constrictive pericarditis (CP) is a highly relevant disease clinically because pericardiectomy represents the only curative therapeutic approach. Previous cardiac surgery or mediastinal radiation may cause CP, however, infectious agents account for a substantial portion of CP. In this report, we present a patient with previous biopsy-proven myocarditis and positive seroconversion against coxsackievirus B3 without clinical evidence of acute pericardial involvement who developed CP after a prolonged period of time. This suggests that infectious particles primarily infecting the myocardium may lead to chronic inflammatory responses of the pericardium, thus causing CP even at late clinical stages. This case emphasizes the important fact that primary myocarditis may not only cause systolic ventricular impairment but may also induce diastolic dysfunction of the heart, either as restrictive cardiomyopathy or, as in this case, through inflammatory involvement of the pericardium, leading to CP.

We aimed to assess the influence of different sirolimus analogues released from a uniform stent platform on re-endothelialisation and vascular healing responses.Bare metal stents (BMS) were coated with a fluoropolymer containing everolimus (EES), sirolimus (SES) or zotarolimus (ZES) to generate drug-eluting stents (DES) with identical stent backbones, drug loads and release kinetics. DES constructs and control BMS were implanted into the iliac arteries of rabbits and were analysed at 14 days by scanning electron microscopy (SEM) and confocal microscopy for en face evaluation of endothelialisation (n=6 for each stent), or at 28 days to determine histomorphometric characteristics (n=11 for each stent). SEM analysis revealed low degrees of strut re-endothelialisation within the DES without differences among groups, while the BMS control showed almost complete endothelialisation. Percent stenosis was significantly reduced in all DES compared to BMS. Strut-based fibrin analysis revealed significantly greater deposition in the DES compared to BMS, with EES showing maximum fibrin deposition among the DES groups.Sirolimus and its derivatives have similar effects on endothelial regrowth and neointimal thickening. The observation of greatest fibrin deposition in the experimental EES group indicates that everolimus may affect vascular healing differently.

To the Editor: We read with interest the recent publication by Umeda et al, “Impact of Sirolimus-Eluting Stent Fracture on 4-Year Clinical Outcomes.”1 The authors present the important finding that stent fracture in sirolimus-eluting stents was associated with a higher major …