18F-Sodium fluoride uptake is associated with severity of atherosclerotic stenosis in stable ischemic heart disease.

BACKGROUND: Increased uptake of 18F-Sodium fluoride (18F-NaF) PET has potential to identify atherosclerotic plaques that are vulnerable to rupture. Whether 18F-NaF PET can evaluate the significance of atherosclerotic plaque in patients with stable coronary artery disease is less clear. We evaluated 18F-NaF PET uptake in coronary arteries in patients without acute coronary artery syndrome to determine the association of 18F-NaF signal uptake with severity of coronary stenosis. METHODS AND RESULTS: We retrospectively identified 114 patients who received both regadenoson stress 82Rb myocardial perfusion PET and 18F-NaF PET study with an average interval of 5 months. Out of this cohort, forty-one patients underwent invasive coronary angiography. In a patient-based analysis, patients with ischemic regadenoson stress 82Rb PET had significantly higher coronary 18F-NaF uptake than patients with normal myocardial perfusion (P < .01). Among the 41 patients who underwent coronary angiography, per-vessel 18F-NaF uptake in both obstructive and nonobstructive coronary arteries was significantly higher than in normal coronary arteries (P < .05) regardless of the severity of coronary calcification. There was poor correlation between calcification and 18F-NaF uptake in coronary arteries (r = 0.41) CONCLUSION: Coronary arterial 18F-NaF uptake is associated with coronary stenosis severity in patients with stable coronary artery disease. 18F-NaF PET studies may be useful for characterizing coronary atherosclerotic plaques.

Targeted Myocardial Hypoxia Imaging Using a Nitroreductase-Activatable Near-Infrared Fluorescent Nanoprobe.

Development of a highly selective and sensitive imaging probe for accurate detection of myocardial hypoxia will be helpful to estimate the degree of ischemia and subsequently guide personalized treatment. However, an efficient optical approach for hypoxia monitoring in myocardial ischemia is still lacking. In this work, a cardiomyocyte-specific and nitroreductase-activatable near-infrared nanoprobe has been developed for selective and sensitive imaging of myocardial hypoxia. The nanoprobe is a liposome-based nanoarchitecture which is functionalized with a peptide (GGGGDRVYIHPF) for targeting heart cells and encapsulating a nitrobenzene-substituted BODIPY for nitroreductase imaging. The nanoprobe can specifically recognize and bind to angiotensin II type 1 receptor that is overexpressed on the ischemic heart cells by the peptide and is subsequently uptaken into heart cells, in which the probe is released and activated by hypoxia-related nitroreductase to produce fluorescence emission at 713 nm. The in vitro response of the nanoprobe toward nitroreductase resulted in 55-fold fluorescence enhancement with the limit of detection as low as 7.08 ng/mL. Confocal fluorescence imaging confirmed the successful uptake of nanoprobe by hypoxic heart cells and intracellular detection of nitroreductase. More significantly, in vivo imaging of hypoxia in a murine model of myocardial ischemia was achieved by the nanoprobe with high sensitivity and good biocompatibility. Therefore, this work presents a new tool for targeted detection of myocardial hypoxia and will promote the investigation of the hypoxia-related physiological and pathological process of ischemic heart disease.

Rationale and design of the Japan-USA harmonized assessment by randomized, multicenter study of OrbusNEich's combo StEnt (Japan-USA HARMONEE): Assessment of a novel DES platform for percutaneous coronary revascularization in patients with ischemic coronary disease and non-ST-elevation acute coronary syndrome.

Tissue trauma associated with stent implantation continues to generate early thrombosis rates of 0.9% to 1.3% for both bare-metal and drug-eluting stent platforms. The Combo sirolimus-eluting stent combines an abluminal, bioabsorbable polymer with a luminal CD34+ antibody designed to capture endothelial progenitor cells. This article describes the design and methods of the HARMONEE trial (NCT02073565), which represents the first randomized controlled trial of the Combo design against a best-in-class contemporary everolimus-eluting stent. Up to 50 sites in Japan and the United States will enroll 286 subjects (271 evaluable) in each of 2 arms, for a total sample size of 572 subjects (542 evaluable). The statistical plan includes both superiority to imputed bare-metal stent control and noninferiority to everolimus-eluting stent on a primary clinical end point of target vessel failure at 1 year. In addition, fractional flow reserve assessment to evaluate the physiology of target vessels in the entire population will augment the end point definition of ischemia-driven target vessel revascularization. Finally, key safety considerations will be evaluated with a subpopulation with optical coherence tomography imaging for strut coverage, late strut malapposition, and plaque volume, as well as serial human antimurine antibody assessments. As the first international prospective randomized coronary intervention study under the "Harmonization by Doing" program, this study represents a unique collaboration between regulators and investigators in Japan and the United States.

A comparative assessment by optical coherence tomography of the performance of the first and second generation of the everolimus-eluting bioresorbable vascular scaffolds.

AIMS: The first generation of the everolimus-eluting bioresorbable vascular scaffold (BVS 1.0) showed an angiographic late loss higher than the metallic everolimus-eluting stent Xience V due to scaffold shrinkage. The new generation (BVS 1.1) presents a different design and manufacturing process than the BVS 1.0. This study sought to evaluate the differences in late shrinkage, neointimal response, and bioresorption process between these two scaffold generations using optical coherence tomography (OCT). METHODS AND RESULTS: A total of 12 lesions treated with the BVS 1.0 and 12 selected lesions treated with the revised BVS 1.1 were imaged at baseline and 6-month follow-up with OCT. Late shrinkage and neointimal area (NIA) were derived from OCT area measurements. Neointimal thickness was measured in each strut. Strut appearance has been classified as previously described. Baseline clinical, angiographic, and OCT characteristics were mainly similar in the two groups. At 6 months, absolute and relative shrinkages were significantly larger for the BVS 1.0 than for the BVS 1.1 (0.98 vs. 0.07 mm² and 13.0 vs. 1.0%, respectively; P = 0.01). Neointimal area was significantly higher in the BVS 1.0 than in the BVS 1.1 (in-scaffold area obstruction of 23.6 vs. 12.3%; P < 0.01). Neointimal thickness was also larger in the BVS 1.0 than in the BVS 1.1 (166.0 vs. 76.4 µm; P < 0.01). Consequently, OCT, intravascular ultrasound, and angiographic luminal losses were higher with the BVS 1.0 than with the BVS 1.1. At 6 months, strut appearance was preserved in only 2.9% of the BVS 1.0 struts, but remained unchanged with the BVS 1.1 indicating different state of strut microstucture and/or their reflectivity. CONCLUSION: The BVS 1.1 has less late shrinkage and less neointimal growth at 6-month follow-up compared with the BVS 1.0. A difference in polymer degradation leading to changes in microstructure and reflectivity is the most plausible explanation for this finding.

Triple-marker cardiac MRI detects sequential tissue changes of healing myocardium after a hydrogel-based therapy.

Regenerative therapies based on injectable biomaterials, hold an unparalleled potential for treating myocardial ischemia. Yet, noninvasive evaluation of their efficacy has been lagging behind. Here, we report the development and longitudinal application of multiparametric cardiac magnetic resonance imaging (MRI) to evaluate a hydrogel-based cardiac regenerative therapy. A pH-switchable hydrogel was loaded with slow releasing insulin growth factor 1 and vascular endothelial growth factor, followed by intramyocardial injection in a mouse model of ischemia reperfusion injury. Longitudinal cardiac MRI assessed three hallmarks of cardiac regeneration: angiogenesis, resolution of fibrosis and (re)muscularization after infarction. The multiparametric approach contained dynamic contrast enhanced MRI that measured improved vessel features by assessing fractional blood volume and permeability*surface area product, T1-mapping that displayed reduced fibrosis, and tagging MRI that showed improved regional myocardial strain in hydrogel treated infarcts. Finally, standard volumetric MRI demonstrated improved left ventricular functioning in hydrogel treated mice followed over time. Histology confirmed MR-based vessel features and fibrotic measurements. Our novel triple-marker strategy enabled detection of ameliorated regeneration in hydrogel treated hearts highlighting the translational potential of these longitudinal MRI approaches.

Efficacy of intramyocardial injection of Algisyl-LVR for the treatment of ischemic heart failure in swine.

BACKGROUND: Progressive thinning and dilation of the LV due to ischemic heart failure (IHF) increases wall stress and myocardial oxygen consumption. Injectable biopolymers implanted in the myocardial wall have been used to increase wall thickness to reduce chamber volume, decrease wall stress, and improve cardiac function. We sought to evaluate the efficacy of a biopolymer (Algisyl-LVR) to prevent left ventricular (LV) remodeling in a swine model of IHF. METHODS: IHF was induced in 11 swine by occluding the marginal obtuse branches of the left circumflex artery. Eight weeks later, Algisyl-LVR was injected into the LV myocardial free wall in five of the 11 animals. Echocardiographic examinations were done every 2weeks for 16weeks. RESULTS: Within eight weeks of treatment, the ejection fraction increased from 30.5%±7.7% to 42.4%±3.5% (treated group) vs. 37.3%±3.8% to 34.3%±2.9% (control), p<0.01. Stroke volume increased from 18.5±9.3mL to 41.3±13.3mL (treated group) vs. 25.4±2.3mL to 31.4±5.3mL (control), p<0.05. Wall thickness in end-diastole of the infarcted region changed from 0.69±0.06cm to 0.81±0.13cm (treated group) vs. 0.73±0.09cm to 0.68±0.11cm (control), p<0.05. Sphericity index remained almost unchanged after treatment, although differences were found at the end of the study between both groups (p<0.001). Average myofiber stress changed from 16.3±5.8kPa to 10.2±4.0kPa (treated group) vs. 15.2±4.8kPa to 17.9±5.6kPa (control), p<0.05. CONCLUSIONS: Algisyl-LVR is an effective strategy that serves as a micro-LV assist device to reduce stress and hence prevent or reverse maladaptive cardiac remodeling caused by IHF in swine.

Severe post-ischemic elongation of the anterior papillary muscle: an unusual cause of mitral insufficiency in a 75-year-old man.

As a complication of myocardial ischemia, severe elongation of the anterior papillary muscle with resultant mitral valve insufficiency is a rare clinical finding. Using echocardiography, we accurately diagnosed this condition in a 75-year-old man. The patient underwent successful plication of the elongated anterior papillary muscle and the implantation of polytetrafluoroethylene neochordae tendineae.

[In-hospital and remote results of the use of sirolimus coated coronary stent CYPHER].

Stents were implanted to 554 previously non-revascularized patients in 703 injured coronary segments; 32% of stented stenoses were complicated; 23% of patients received 2-4 stents. Immediate success was 100% with no cases of acute stent thrombosis. Rate of in-hospital subacute thrombosis and non-Q-wave myocardial infarction was 0.2%. Survival without restenosis, angina, myocardial infarction and repeat revascularization during follow up (mean duration 257+/-107 days) was 94%, restenosis rate -- 5.6%. Six patients with in-stent restenosis were successfully revascularized. All 108 patients followed for 27 months were alive by the end of this term.

PEGylated nanoliposomes encapsulating angiogenic peptides improve perfusion defects: Radionuclide imaging-based study.

INTRODUCTION: Although liposomes hold promise for cancer therapy, the effectiveness of treating myocardial ischemia by promoting angiogenesis has yet to be proved. Nanoliposomes loaded with therapeutic agents can effectively target ischemic myocardium via enhanced permeability and retention. Surface polyethylene glycol (PEG) modification can further facilitate effective targeting by prolonging liposomal circulation. This study aimed to determine whether PEGylated nanoliposomes are effective in facilitating targeted drug delivery and treating myocardial ischemia. METHODS: Rats subjected to 30min of myocardial ischemia were given (99m)Tc-hexamethylpropyleneamine oxime- or (99m)Tc-diethylenetriamine pentaacetate-labeled liposomes with mean diameters of ~100nm or ~600nm with or without PEG modifications to determine the extent of myocardial uptake in the different conditions. Therapeutic effectiveness was assessed by studying changes in myocardial perfusion defects with (99m)Tc-tetrofosmin autoradiography and vascular density with immunohistochemistry at 7days post-treatment. RESULTS: The liver and spleen showed the largest capacity for liposome uptake. Uptake by the liver and spleen was more pronounced when the liposomes were larger. Conversely, myocardial liposome uptake was significantly greater when the liposomes were ~100nm rather than ~600nm in diameter. Surface modification with PEG significantly augmented myocardial uptake of ~100nm liposomes. PEG modification did not affect the size dependence. To investigate therapeutic efficacy, hearts subjected to ischemia received PEGylated nanoliposomes encapsulated with angiogenic peptides. Our data demonstrated that PEGylated nanoliposomes loaded with angiogenic peptides improved myocardial perfusion defects and increased vascular density. A 10-fold increase in liposomal concentration did not further benefit myocardial ischemia. CONCLUSIONS: Liposomal angiogenic formulation with size control and PEG modification may be effective treatment strategy for myocardial ischemia. Increasing the concentration of liposomes does not necessarily benefit myocardial ischemia.

Impact of platelet glycoprotein IIb/IIIa Inhibition on the paclitaxel-eluting stent in patients with stable or unstable angina pectoris or provocable myocardial ischemia (a TAXUS IV substudy).

Whether the benefits that glycoprotein IIb/IIIa inhibitors confer in patients who undergo bare metal stent implantation extend to drug-eluting stents is unknown. We performed a prespecified subgroup analysis of the TAXUS IV study population to examine the effect of procedural glycoprotein IIb/IIIa inhibition during paclitaxel-eluting stent implantation on periprocedural creatine kinase-MB (CK-MB) levels. Glycoprotein (GP) IIb/IIIa inhibitors were administered to 57.7% of patients who had been randomized to receive the TAXUS stent and to 56.7% of those who had been randomized to receive the control stent. Among patients who received the TAXUS stent, the rate of CK-MB increases of >3 times the normal level was 2.6-fold higher in those who received a GP IIb/IIIa inhibitor than in those who did not (11.4% vs 4.4%, p = 0.0015). Composite rates of major adverse cardiac events and target vessel failure were also higher at 1 month in the GP IIb/IIIa group. By multivariate analysis, use of GP IIb/IIIa inhibitors during stenting with the TAXUS stent was an independent predictor of CK-MB increases >3 times the normal level. Further studies are warranted.

Impact of obesity on revascularization and restenosis rates after bare-metal and drug-eluting stent implantation (from the TAXUS-IV trial).

The effect of obesity on repeat coronary revascularization and restenosis in patients who undergo stent implantation has not been reported. We therefore examined the database from the multicenter randomized TAXUS-IV trial to determine the effect of body mass index (BMI) on outcomes after bare-metal and drug-eluting stent implantation. In TAXUS-IV, patients were randomized to receive a slow-release, polymer-based, paclitaxel-eluting stent or a bare-metal stent. Outcomes were stratified by baseline BMI. Of the 1,307 randomized patients who had documented BMI, 233 (17.8%) had normal weight (BMI <25 kg/m2), 531 (40.6%) were overweight (BMI < or =25 to 30 kg/m2), and 543 (41.5%) were obese (BMI > or =30 kg/m2). Patients who had been assigned to receive bare-metal stents and were overweight and obese compared with those who had normal weight had higher rates of 9-month binary restenosis (29.2% and 30.5% vs 9.3%, respectively; p = 0.01) and 1-year major adverse cardiac events (20.8% and 23.2% vs 11.1%, respectively; p = 0.02), whereas rates of these events did not differ significantly among those who received a paclitaxel-eluting stent (7.6% and 9.3% vs 4.9%, respectively for binary restenosis; p = 0.65; 11.3% and 10.4% vs 10.1%, respectively; p = 0.82 for major adverse cardiac events). By multivariate analysis, BMI > or =30.0 kg/m2 independently predicted binary restenosis (hazard ratio 4.26, p = 0.005), 1-year target vessel revascularization (hazard ratio 1.95, p = 0.04), and major adverse cardiac events (hazard ratio 1.95, p = 0.004) in patients who received bare-metal stents but not paclitaxel-eluting stents. In conclusion, obesity is an important risk factor for clinical and angiographic restenosis and for composite major adverse cardiac events in patients who receive bare-metal stents. Paclitaxel-eluting stents attenuate the increased risk associated with obesity, such that the intermediate-term prognosis after percutaneous coronary intervention is independent of weight.

Symptoms of patients with silent ischemia as detected by thallium stress testing.

This study was undertaken to determine whether patients with silent ischemia (SI) (a positive thallium stress test without chest pain) have nonchest-pain symptoms that might serve as "anginal equivalents." Two hundred ninety-four individuals on completing a stress test were requested to score ten symptoms on a questionnaire (0 absent; 3 severe). Forty-three with a positive test had pains (chest, back, arm, and/or jaw) (no SI), whereas 93 with a positive test did not (SI). Patients with SI and patients without SI did not differ as to age, gender, or clinical features (including presence of diabetes or a history of myocardial infarction), but patients with SI were less likely to report a history of effort-related chest pains. Patients with SI exercised longer and had a higher peak heart rate. Patients were comparable with respect to myocardial ischemia (ST segment depression, double product, thallium lung uptake, and positive thallium scintigrams) and severity of coronary disease. Patients with SI complained less of weakness (p < 0.02) and tended to have lower overall symptom scores (4.2 +/- 0.3 vs 5.4 +/- 0.6), but breathlessness was comparable for both groups. On multivariate analysis, no nonanginal symptom was associated with SI. Only absence of a history of chest pain with activity and longer exercise time were related to SI. Patients with SI have similar clinical features as those with angina but tend to be less symptomatic with myocardial ischemia even for symptoms other than chest pain.

Papillary muscle sling: a new functional approach to mitral repair in patients with ischemic left ventricular dysfunction and functional mitral regurgitation.

BACKGROUND: In patients with ischemic left ventricular dysfunction (LVD) and functional mitral regurgitation (FMR), restoring a more normal alignment between mitral annulus and laterally displaced papillary muscles (PM) may be beneficial in terms of mitral repair and regional dynamics. METHODS: Ten patients, 29 to 78 years old, with an ejection fraction of 25% to 45%, pulmonary hypertension greater than 60, and New York Heart Association Class III-IV, had their PMs drawn together by a tightly encircling loop using a 4-mm Gore-Tex tube. Associated mitral annuloplasty rings were only moderately undersized. Efficiency was essentially evaluated on reversal of mitral tenting and control of FMR. RESULTS: Postoperative echocardioraphy revealed changes in "tenting effect" from 14 +/- 2.8 mm to 4 +/- 1.41 mm. Regurgitation is none to trivial in 9 patients, and mild in 1 patient. The posterior left ventricular wall between the PMs is shortened as a result of the surgical remodeling and may be beneficial on local dynamics. CONCLUSIONS: Joining the PM side-by-side has an obvious immediate effect on mitral leaflet mobility by suppressing the tethering due to displacement of the PM. An eventual result on local ventricular dynamics needs confirmation.

Evaluation of a new ultrasound contrast agent (AI-700) using two-dimensional and three-dimensional imaging during acute ischemia.

BACKGROUND: A new intravenous contrast agent, AI-700, was evaluated to determine whether a bolus injection could be used to detect myocardial perfusion abnormalities during acute ischemia by using 2-dimensional (2D) and 3-dimensional (3D) myocardial contrast echocardiography. METHODS: 2D MCE was performed in 14 closed-chest dogs during coronary occlusion by using both continuous and triggered gray scale harmonic imaging and triggered power Doppler imaging. 3D MCE (open-chest) and nuclear perfusion imaging were performed in 10 of the 14 dogs. Postmortem triphenyl tetrazolium chloride (TTC) staining was performed to verify infarction. RESULTS: Thirteen of the 14 dogs had infarct by TTC; all 10 that had nuclear imaging showed a perfusion defect. Of the 13 dogs that had infarction, perfusion defects were detected in all (13 of 13) by gray scale harmonic imaging (sensitivity = 100%), and in 11 of 13 by power Doppler imaging (sensitivity = 85%). All 10 dogs that had nuclear imaging showed perfusion defects by gray scale harmonic imaging (sensitivity = 100%) and 8 of 10 by power Doppler imaging (sensitivity = 80%). The perfusion defect size, derived from 3D imaging (25% +/- 12%) correlated well with that from nuclear imaging (24% +/- 12%) (y = 0.9x + 3.8, r = 0.96, mean difference = 1.3% +/- 2.6%). The perfusion defect mass by 3D (22 +/- 14 g) also correlated well with the infarct mass by TTC staining (24 +/- 16 g) (y = 0.8x + 2.9, r = 0.89, P <.001, mean difference = -2.8 +/- 7.6 g). CONCLUSION: After a single bolus of AI-700, both 2D and 3D MCE could accurately detect perfusion defects representing the area at risk of infarction during acute ischemia compared with nuclear imaging and predicted the size of infarction as verified by TTC staining.

Italian BiodivYsio open registry (BiodivYsio PC-coated stent): study of clinical outcomes of the implant of a PC-coated coronary stent.

UNLABELLED: Rapid technological developments have made new materials available for percutaneous coronary intervention procedures. The coronary stent in particular has undergone progressive structural improvements leading to the recent availability of a third generation of stents, namely, coated stents. The rapid evolution of the stent has often made its evaluation problematical, since trials are frequently confined to small groups of patients in single centers. The purpose of this registry was to verify the safety and efficacy of the BiodivYsio stent (a stent coated with phosphorylcholine polymer) in a broad population of patients who reflect the daily reality of coronary intervention in a cardiac catheterization laboratory. METHODS AND RESULTS: The registry was designed to collect the principal angiographic and clinical data of a consecutive series of Oreal worldO patients. Patients were treated with a BiodivYsio stent (Biocompatibles, Galway, United Kingdom) in 12 centers (11 Italian and 1 Swiss) between January 1998 and January 1999. Procedural, in-hospital, 30-day and six-month follow-up data were collected. The monitoring, data entry and statistical analyses were carried out by an independent center. During the study, 218 patients were enrolled; 165 (76%) male and 53 (24%) female, with an average age of 61.6 +/- 9.4 years (range, 36Eth 84 years). A total of 258 stents were implanted in 233 lesions (1.1 stents per lesion), of which 233 (90%) were the BiodivYsio PC coated stent, the remaining 25 implants were of other stent types. The percutaneous transluminal coronary angioplasty and stenting procedure were carried out in 109 (50%) patients with unstable angina, 65 (30%) with stable angina, 29 (13%) with acute myocardial infarction, and 15 (7%) patients with silent ischemia. Procedural success was achieved in 217/218 (99.5%) patients. Optimal results were achieved in 212 (97.7%) patients. In 34 (15.6%) cases, patients were treated with periprocedural abciximab. During the hospitalization period, one (0.4%) death occurred on day 7 due to subacute occlusion of the stent, and 3 (1.4%) myocardial infarctions were reported. At 30-day follow-up, 211 (97.2%) patients were asymptomatic, as were 189 (87%) patients at clinical follow-up at 6 months. CONCLUSIONS: This study evaluated the safety and efficacy of a third-generation stent. The results demonstrate a high procedural success rate and a low incidence of major adverse cardiac events at short- and medium-term follow-up. It appears that the BiodivYsio stent should be considered safe in clinical and/or anatomical situations with a high risk of complications, confirming the hypothesis that PC may have non-thrombogenic properties. To corroborate these results, an appropriately designed study would be required to measure the stentOs efficacy in the most suitable clinical context, i.e., clinical situations that are at the highest risk of ischemic relapse.

The use of antibody modified liposomes loaded with AMO-1 to deliver oligonucleotides to ischemic myocardium for arrhythmia therapy.

MicroRNA-1 (miR-1) has been found in cardiac and skeletal tissues. It is overexpressed in ischemic cardiac tissues. Down-regulation of miR-1 could relieve arrhythmogenesis by the anti-miR-1 antisense oligonucleotides (AMO-1). To increase the therapeutic efficiency and inhibit off-target effects of AMO-1, here we explored anti-cardiac troponin I (cTnI) antibody modified liposomes loading with AMO-1 (cT-A-LIP) to deliver the oligonucleotides to ischemic myocardium tissues. Liposomal cytotoxicity was assessed by MTT assay. The targeting abilities to foci were evaluated by in vivo imaging. The uptake and bio-distribution in vitro were observed by live cell station and flow cytometry, respectively. The anti-arrhythmic effects of cT-A-LIP in vivo were evaluated by electrocardiograms (ECG), immunohistochemistry, real-time PCR and patch-clamp recording. Immunohistochemistry showed that cTnI expression had a peak at the third day after myocardial infarction (MI). After cT-LIP administration via tail vein, accumulation of fluorescent trackers in the ischemic foci was significantly increased more than that of LIP. In addition, after cT-A-LIP administration, the ischemic arrhythmias were recovered and ST segment in ECG was elevated nearly back to normal. Compared with MI group, miR-1 expression was significantly down-regulated while Kir2.1 and CX43 protein expression were increased. Patch-clamp recordings showed that cT-A-LIP as well as AMO-1 incubation increased K(+) current density in guinea pigs ventricular cardiomyocytes acting on repolarized membrane potential. In conclusion, the cT-A-LIP not only delivered AMO-1 to ischemic myocardium in MI rats, but validated AMO-1 on relieving ischemic arrhythmia by silencing of miR-1 in ischemic myocardium and restoring the depolarized resting membrane potential (RMP) in MI rats.

The effect of polymer degradation time on functional outcomes of temporary elastic patch support in ischemic cardiomyopathy.

Biodegradable polyurethane patches have been applied as temporary mechanical supports to positively alter the remodeling and functional loss following myocardial infarction. How long such materials need to remain in place is unclear. Our objective was to compare the efficacy of porous onlay support patches made from one of three types of biodegradable polyurethane with relatively fast (poly(ester urethane)urea; PEUU), moderate (poly(ester carbonate urethane)urea; PECUU), and slow (poly(carbonate urethane)urea; PCUU) degradation rates in a rat model of ischemic cardiomyopathy. Microporous PEUU, PECUU or PCUU (n = 10 each) patches were implanted over left ventricular lesions 2 wk following myocardial infarction in rat hearts. Infarcted rats without patching and age-matched healthy rats (n = 10 each) were controls. Echocardiography was performed every 4 wk up to 16 wk, at which time hemodynamic and histological assessments were performed. The end-diastolic area for the PEUU group at 12 and 16 wk was significantly larger than for the PECUU or PCUU groups. Histological analysis demonstrated greater vascular density in the infarct region for the PECUU or PCUU versus PEUU group at 16 wk. Improved left ventricular contractility and diastolic performance in the PECUU group was observed at 16 wk compared to infarction controls. The results indicate that the degradation rate of an applied elastic patch influences the functional benefits associated patch placement, with a moderately slow degrading PECUU patch providing improved outcomes.

First human trial of KW39 slotted-tube stents: for percutaneous coronary intervention.

The KW39 stent is a balloon-expandable, stainless-steel, slotted-tube stent, newly designed to adjust to the shape of the coronary arteries. We evaluated the clinical efficacy and safety of KW39 stent-based percutaneous coronary interventions in human native coronary arteries. A total of 105 patients (110 lesions), with a diagnosis of stable angina, acute coronary syndrome, or asymptomatic myocardial ischemia, were included in this prospective study. The primary endpoint was the target-lesion revascularization rate at the conclusion of a 6-month follow-up period. The secondary endpoints were the rates of technical and procedural success and the rate of major adverse cardiac events (defined as cardiac death, myocardial infarction, and target-lesion revascularization) in the course of the 6 months after stent placement. The 6-month target-lesion revascularization rate was 8.6%. The KW39 stent was highly satisfactory in regard to all secondary endpoint comparisons. Binary (>50%) in-stent restenosis was observed in 22 of 110 lesions (20%). The mean diameter stenosis at 6 months after percutaneous coronary intervention was 35.1% ± 14.4%, and the mean late lumen loss was 1.06 ± 0.48 mm. Stepwise multivariate analysis showed probable causal associations between adverse local environments for stent implantation and the subsequent need for target-lesion revascularization. We conclude that KW39 stent implantation was technically feasible and clinically safe in the patient population that we studied. The results of the safety endpoints, including cardiac death and acute myocardial infarction, were acceptable.

Frequency of coronary artery bypass grafting following implantation of a paclitaxel-eluting or a bare-metal stent into a single coronary artery.

Limited data are available on the relative effect of drug-eluting versus bare-metal stents on the requirement for subsequent coronary artery bypass grafting (CABG). The aim of this study was to evaluate the incidence and predictors of CABG after bare-metal and paclitaxel-eluting coronary stent implantation. A patient-level, pooled analysis was conducted of 2,736 patients from 3 double-blind, randomized trials comparing the slow-release paclitaxel-eluting Taxus stent with an otherwise identical bare-metal stent control in single de novo coronary lesions, with 5-year follow-up. The rate of target lesion revascularization by CABG (TLR-CABG) was reduced from 4.1% in patients with bare-metal stents to 1.4% in those with Taxus stents (p <0.001). The use of the Taxus stent was the strongest predictor of freedom from TLR-CABG on multivariate analysis (hazard ratio 0.33, p <0.001). Significant reductions in TLR-CABG with Taxus compared with bare-metal stents were seen in the treatment of left anterior descending artery lesions (6.1% vs 1.8%, p <0.001) and non-left anterior descending artery lesions (2.8% vs 1.3%, p = 0.037), in patients with diabetes (6.0% vs 1.0%, p <0.01), and in those without diabetes (3.5% vs 1.6%, p <0.01). In conclusion, referral to CABG is significantly less common after stenting single coronary lesions with Taxus compared with bare-metal stents. The relative reductions in TLR-CABG of 54% in patients without diabetes, 87% in patients with diabetes, 70% in left anterior descending artery lesions, and 54% in non-left anterior descending artery lesions with Taxus compared with bare-metal stents should be considered during stent selection.