Polymer-free biolimus-A9-coated stent for primary percutaneous coronary intervention.

BACKGROUND: The polymer-free biolimus-A9 drug-coated stent (DCS) was reported to have superior safety and efficacy outcomes compared with a bare metal stent in the LEADERS FREE trial of high-bleeding-risk patients with acute coronary syndrome and on dual antiplatelet treatment (DAPT) for 1 month. The aim of this investigation was to evaluate the DCS in a consecutive cohort of patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). METHODS: We analyzed data from 164 consecutive STEMI patients who underwent PPCI using the DCS at our institution. The primary efficacy endpoint was clinically indicated target lesion revascularization (ciTLR); the primary safety endpoint was a composite of cardiac death, myocardial infarction, and definite/probable stent thrombosis. Clinical outcomes at 1 year are presented here. RESULTS: The mean age of the patients was 61.5 ± 15.5 years, and 86.6% were male. The median symptom-to-balloon-time was 55 min. In 57.9% of patients (n = 95), the infarct had an anterior location. PPCI achieved Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in 163 of 164 patients (99.4%). All patients were prescribed DAPT for 1 year. At 1 year, ciTLR occurred in 1.2% of patients, the primary safety endpoint was reached in 4.3% of patients, and definite stent thrombosis was noted in 0.6% of patients. CONCLUSION: In this consecutive real-world cohort of patients, the DCS was safe and efficacious when used for PPCI in patients with STEMI.

2-year follow-up of Nevo RES-elution I, a randomisedmulticentre comparison of the Nevo Sirolimus-eluting coronarystent system using RES technology with the Taxus LibertéPaclitaxel-eluting stent

Aims: The NEVO™ sirolimus eluting coronary stent is designed to improvelong-term PCI safety by combining sirolimus release from reservoirs withbioabsorbable polymer to reduce spatial and temporal polymer exposure.Absorption of drug and polymer within approximately three months limits theduration of vessel wall exposure to the polymer. Thereafter, only a biologically inertbare-metal platform remains. The NEVO™ stent was first evaluated in the multicenterrandomised NEVO RES-Elution I trial which demonstrated its superiority tothe TAXUS Liberté Paclitaxel - eluting stent.

Sirolimus-eluting stents, bare metal stents or coronary artery bypass grafting for patients with multivessel disease including involvement of the proximal left anterior descending artery: analysis of the Arterial Revascularization Therapies study part 2 (ARTS-II).

OBJECTIVE: The The Arterial Revascularization Therapies Study (ARTS)-II trial found no differences in survival or overall adverse events between sirolimus-eluting stents (SES) and the surgical arm of ARTS-I. Nevertheless, existing data suggest that patients with disease of the proximal left anterior descending artery (LAD) may derive particular benefit from coronary artery bypass grafting (CABG). We therefore analysed the clinical outcome of patients in ARTS-I and ARTS-II with proximal LAD involvement. DESIGN: Multicentre observational study. SETTING: Forty-five European academic hospitals. PATIENTS: Patients with multivessel coronary artery disease. INTERVENTIONS: Patients in ARTS-II with proximal LAD disease treated with SES (289/607, 48%) were compared with 187/600 (31%) bare metal stent patients (ARTS-I BMS) and 206/605 (34%) surgical patients (ARTS-I CABG) with proximal LAD involvement from ARTS-I. MAIN OUTCOME MEASURES: Major adverse cardiac and cerebrovascular events after 3 years. RESULTS: The Arterial Revascularization Therapies study part 2 (ARTS-II) subgroup had better survival than both ARTS-I groups (ARTS-II 98.6% vs ARTS-I BMS 95.7%, p = 0.05 and vs ARTS-I CABG 94.7%, p = 0.01) and lower rates of the hard clinical composite endpoint of death or non-fatal myocardial infarction (ARTS-II 3.1% vs ARTS-I BMS 9.6%, p = 0.002 and vs ARTS-I CABG 9.7%, p = 0.002). Although the ARTS-I CABG patients had a lower need for repeat revascularisation than ARTS-II (5.3% vs 13.1%, p = 0.002), the overall composite adverse event rates (death, myocardial infarction, stroke or any repeat revascularisation) were not significantly different between the ARTS-I CABG and ARTS-II patients (15.0% vs 18.0%, p = 0.4). CONCLUSIONS: SES are not inferior to CABG or bare metal stents for the treatment of patients with multivessel coronary disease including involvement of the proximal LAD.

Impact of late incomplete stent apposition after sirolimus-eluting stent implantation on 4-year clinical events: intravascular ultrasound analysis from the multicentre, randomised, RAVEL, E-SIRIUS and SIRIUS trials.

BACKGROUND: The impact of incomplete stent apposition (ISA) after drug-eluting stent implantation determined by intravascular ultrasound (IVUS) on late clinical events is not well defined. OBJECTIVE: To evaluate the clinical impact of ISA after sirolimus-eluting stent (SES) placement during a follow-up period of 4 years. DESIGN: Pooled analysis from the RAVEL, E-SIRIUS and SIRIUS trials, three randomised, multicentre studies comparing SES and bare-metal stents (BMS). METHODS: IVUS at angiographic follow-up was available in 325 patients (SES: n = 180, BMS: n = 145). IVUS images were reviewed for the presence of ISA defined as one or more unapposed stent struts. Clinical follow-up was available for a 4-year period in all patients. Frequency, predictors and clinical sequel of ISA at follow-up after SES and BMS implantation were determined. RESULTS: ISA at follow-up was more common after SES (n = 45 (25%)) than after BMS (n = 12 (8.3%), p<0.001). Canadian Cardiology Society class III or IV angina at stent implantation (odds ratio (OR) = 4.69, 95% CI 2.15 to 10.23, p<0.001) and absence of diabetes (OR = 3.42, 95% CI 1.05 to 11.1, p = 0.041) were predictors of ISA at follow-up after SES placement. Rate of myocardial infarction tended to be slightly higher for ISA than for non-ISA patients. When SES patients only were considered, major adverse cardiac event free survival at 4 years was identical for those with and without ISA at follow-up (11.1% vs 16.3%, p = 0.48). CONCLUSIONS: ISA at follow-up is more common after SES implantation than after BMS implantation. Considering the current very sensitive IVUS definition, ISA appears to be an IVUS finding without significant impact on the incidence of major adverse cardiac events even during long-term follow-up.

Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis.

UNLABELLED: Balloon catheters filled with liquid radioisotopes provide excellent dose homogeneity for intracoronary radiation therapy but are associated with risk for rupture or leakage. We hypothesized that the safety of liquid-filled balloons may be improved once positron emitters with half-lives below 2 h are used instead of the high-energy beta-emitters 166Ho, 186Re, or 188Re, all of which have a longer half-life of at least 17 h. METHODS: To support this concept, the suitability of 18F (half-life, 109.8 min), 68Ga (half-life, 67.6 min), 11C (half-life, 20.4 min), 13N (half-life, 9.97 min), and 15O (half-life, 2.04 min) for intracoronary radiation therapy was evaluated. Potential tissue penetration of positron radiation was assessed in a series of phantom experiments using Gafchromic film. Antiproliferative efficacy of positrons emitted by 68Ga was investigated in vitro using cultured bovine aortic smooth muscle cells (BASMCs), and was compared with gamma-radiation emitted by 137Cs. To characterize the remaining risk, we estimated radiotoxicity after accidental intravascular balloon rupture on the basis of tabulated isotope-specific doses (ICRP 53) and compared these values with 188Re. RESULTS: Half-dose depth of tissue penetration measured in phantom experiments was 0.29 mm for 18F, 0.42 mm for 11C, 0.54 mm for 13N, 0.79 mm for 15O, and 0.9 mm for 68Ga. Irradiation of cultured BASMCs with positron radiation (68Ga) induced dose-dependent inhibition of proliferation with complete proliferative arrest at doses exceeding 6 Gy. ED(50) and ED(80) were 2.5 +/- 0.4 Gy (mean +/- SD) and 4.4 +/- 0.8 Gy, respectively. Antiproliferative efficacy was equal to that of the 662-keV gamma-radiation emitted by 137Cs (ED(50), 3.8 +/- 0.2 Gy; ED(80), 8.0 +/- 0.3 Gy). Estimates made for patient whole-body and organ doses were generally below 50 mSv/1.85 GBq for all investigated positron emitters. The same dose estimates for 188Re were 6-20 fold higher. CONCLUSION: Among the studied radioisotopes, 68Ga is the most attractive source for liquid-filled balloons because of its convenient half-life, sufficient positron energy (2.92 MeV), documented antiproliferative efficacy, and uncomplicated availability from a radioisotope generator. The safety profile for 68Ga is significantly better than that of 188Re, which suggests this radioisotope should be evaluated further in preclinical studies.

Liquid-filled balloon brachytherapy using (68)Ga is effective and safe because of the short 68-minute half-life: results of a feasibility study in the porcine coronary overstretch model.

BACKGROUND: Liquid-filled balloons for coronary brachytherapy provide significant advantages over solid sources in dose homogeneity but carry the risk of life-threatening radiointoxication after balloon rupture and laboratory contamination in case of a spill. We hypothesized that the positron emitter (68)Ga, with a half-life of only 68 minutes, was well suited to overcome these safety obstacles while providing full therapeutic efficacy. METHODS AND RESULTS: The feasibility, efficacy, and safety of (68)Ga liquid-filled balloon brachytherapy were investigated in the porcine coronary overstretch model. Four groups of 5 balloon-induced coronary lesions were irradiated with 8, 12, 16, and 24 Gy targeted to the adventitia. Ten unirradiated lesions served as controls. Segments treated with 16 or 24 Gy exhibited marked suppression of neointimal proliferation at 28-day follow-up, with quantitative parameters of intraluminal proliferation reduced to <20%. This beneficial effect was not compromised by untoward edge effects. Uninjured but irradiated vessels did not show histological signs of radiation damage. The (68)Ga whole-body dose due to balloon rupture was estimated to be 5 rem/50 mCi treatment activity and compared favorably with that of (188)Re (78 rem/50 mCi). CONCLUSIONS: (68)Ga positron radiation suppresses neointimal proliferation at doses of 16 and 24 Gy. This biological efficacy, coupled with the attractive safety profile, suggests the selection of (68)Ga as an attractive isotope for liquid-filled balloon brachytherapy.

Experimental validation of a new coronary guide wire labeled with rubidium 81/krypton 81m for continuous assessment of myocardial blood flow.

BACKGROUND: The rubidium 81/krypton 81m method was suggested for assessment of myocardial blood flow (MBF) three decades ago. This study investigates the novel concept of using 81Rb-/81mKr-labeled coronary guide wires with wire-attached 81Rb activity and diffusable 81mKr gas for assessment of lesion-specific impairment of MBF by evaluation of the 81Rb/81mKr activity ratio. The feasibility of wire production is tested, and application of the method is investigated in the canine model. METHODS AND RESULTS: Conventional coronary guide wires for angioplasty (0.014 in) were labeled with radioactive 81Rb/81mKr by ion bombardment of the wire tip. A total of 16 of the 18 wires labeled in series showed successful 81Rb fixation in combination with free 81mKr gas diffusability during quality control measurements. The suitability of the wires to assess MBF in combination with an external gamma ray detector was investigated in open-chested dogs. Electromagnetic measurement of coronary blood flow (CBF) was used as reference, providing a signal that is directly linked to volumetric MBF. The 81Rb/81mKr ratio tracked changes in CBF reliably in all 6 dogs. The found linear dependence of measured 81Rb/81mKr count rates on measured CBF supports the modeling assumptions made to apply the theoretic basis of the 81Rb/81mKr technique to 81Rb-labeled coronary guide wires. CONCLUSION: 81Rb-/81mKr-labeled coronary guide wires provide a signal that indicates volumetric MBF directly. This unique capability may qualify the technique as a valuable tool for research purposes and as an attractive method for invasive cardiology at centers where the logistic arrangements for short-lived isotope supply are provided.

Pharmacokinetics and consistency of pericardial delivery directed to coronary arteries: direct comparison with endoluminal delivery.

BACKGROUND AND HYPOTHESIS: Pharmacologic modulation of the contents of the pericardial space has been shown to influence the response of coronary arteries to balloon injury. Endoluminal (EL) local delivery of various drugs into coronaries has been found to be limited by short residence time, as well as by highly variable deposited agent concentration. We hypothesized that compounds placed into the pericardial space (P) would penetrate into coronary tissue with greater consistency than seen after EL delivery and provide for prolonged coronary exposure to agents. METHODS AND RESULTS: 125I-labeled basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), albumin, or 131I-labeled diazeniumdiolated albumin (NONO-albumin) were delivered as model/therapeutic proteins into the porcine pericardial space (n = 15 pigs) or into coronaries using an EL delivery catheter (n = 48 arteries). In subjects receiving 125I-labeled proteins, the delivery target or mid-regions of the left anterior descending (LAD) and left circumflex (LCx) arteries were harvested at 1 h or 24 h for gamma-counting and autoradiography, and fractional intramural delivery (FID) or retention measured as percent agent in 100 mg artery/agent in infusate for both time points. In the animals receiving 131I-labeled NONO-albumin, serial gamma imaging was employed to evaluate the rate of redistribution in individual animals following either pericardial or endoluminal delivery. At 1 h, FID values ranged from 0.00064 to 0.0052% for P delivery (median 0.0022%), and from 0.00021 to 6.7 for EL delivery (median 0.27%). At 24 h, FID values ranged from 0.00011 to 0.003 for P delivery (median 0.0013), and from 0.0002 to 1.4 for EL delivery. The estimated T1/2 for bFGF redistribution from the vascular tissue was 22 h (P) and 7 h (EL), respectively, while the directly determined T1/2 values for NONO-albumin redistribution from the delivery region were 22.2 h (P) and 2.5 h (EL). CONCLUSIONS: These data show that pericardial fluid contents can access coronary arteries with intramural concentrations which typically vary by 10-15-fold, while EL delivery results in a remarkably wide intramural concentration range with up to 33,000-fold variability. The apparent redistribution rate is more rapid following EL delivery, possibly due to sustained diffusive tissue loading from the pericardial space. Pericardial delivery appears to offer substantial advantages over EL administration with respect to residence time and reproducibility.

High resolution ECG and left ventricular volume after acute myocardial infarction.

The presence of ventricular late potentials (LPs) early after acute myocardial infarction (AMI) was recently reported to correlate with left ventricular dilatation subsequent to AMI. We assessed prospectively the relationship between LP (time domain) in the late phase of AMI and left ventricular end-diastolic volume (EDV) measured by equilibrium radionuclide angiocardiography 4 weeks and 12 months after AMI. In 80 consecutive patients 4 weeks and 12 months after thrombolytic therapy for AMI, LP and EDV were determined (EDV1, EDV2). There was no significant correlation between QRS duration (r = 0.18), RMS40 (r = 0.08), or LAS40 (r = 0.1) and EDV1 or EDV2 in patients with or without LP at baseline. In both groups (patients with [n = 15] and without LP [n = 65]), EDV1 and EDV2 were comparable (128 +/- 32 mL vs 126 +/- 35 mL; 114 +/- 40 mL vs 117 +/- 36 mL; P = NS). In addition, there was no significant difference between EDV1 and EDV2 in patients who developed new LP (n = 6) or lost LP (n = 9) 12 months after AMI. In contrast to LP in the very early phase after AMI, there seems to be no significant correlation between the high resolution ECG in the late phase after thrombolytic therapy for AMI and left ventricular EDV.

Myocardial metabolic imaging by means of fluorine-18 deoxyglucose/technetium-99m sestamibi dual-isotope single-photon emission tomography.

The detection of preserved glucose uptake in hypoperfused dysfunctional myocardium by fluorine-18 deoxyglucose (FDG) positron emission tomography (PET) represents the method of choice in myocardial viability diagnostics. As the technique is not available for the majority of patients due to cost and the limited capacity of the PET centres, it was the aim of the present work to develop and test FDG single-photon emission tomography (SPET) with the means of conventional nuclear medicine. The perfusion marker sestamibi (MIBI) was used together with the metabolic tracer FDG in dual-isotope acquisition. A conventional SPET camera was equipped with a 511-keV collimator and designed to operate with simultaneous four-channel acquisition. In this way, the scatter of 18F into the technetium-99m energy window could be taken into account by a novel method of scatter correction. Thirty patients with regional wall motion abnormalities at rest were investigated. The results of visual wall motion analysis by contrast cine-ventriculography in nine segments/heart were compared with the results of quantitative scintigraphy. The scintigraphic patterns of MIBI and FDG tracer accumulation were defined as normal, matched defects and perfusion-metabolism mismatches. Spatial resolution of the system was satisfactory, with a full width at half maximum (FWHM) of 15.2 mm for 18F and 14.0 mm for 99mTc, as measured by planar imaging in air at 5 cm distance from the collimator. Image quality allowed interpretation in all 30 patients. 88% of segments without relevant wall motion abnormalities presented normal scintigraphic results. Seventy-five akinetic segments showed mismatches in 27%, matched defects in 44% and normal perfusion in 29%. We conclude that FDG-MIBI dual-isotope SPET is technically feasible with the means of conventional nuclear medicine. Thus, the method is potentially available for widespread application in patient care and may represent an alternative to the 201Tl reinjection technique.

Myocardial perfusion measured by dual-isotope acquisition of 81rubidium/81mkrypton: an experimental verification of the method.

PURPOSE: The purpose of the study was to verify that the 81Rubidium/81mkrypton (81Rb/81mKr) method allows the quantitative measurement of myocardial perfusion. PRINCIPLE: The potassium analogous cation 81Rb is accumulated in the myocardium by the cell membrane-bound Na-K-ATPase. After accumulation an intracellular equilibrium establishes between 81Rb and its radioactive daughter nuclide 81mKr. The flow-sensitive method evaluates the disturbance of this equilibrium by perfusion which washes out the short-lived diffusable daughter nuclide 81mKr while the mother nuclide 81Rb remains cell-bound. METHODS: Isolated rabbit hearts were prepared in a modified Langendorff technique which allowed quantitative collection of the coronary sinus efflux. The myocardium was labeled with pure 81Rb by bolus injection into the aortic cannula. Spectroscopic measurements of 81Rb and 81mKr gamma radiation were performed using a germanium detector. Perfusion was varied in the range between 0 and 4 ml/min/g. The activity ratio 81Rb/81mKr was determined and compared with coronary sinus effusion. RESULTS: 81Rb/81mKr activity ratio was closely related (r = 0.98) to perfusion as described by the predicted equation Rb/Kr = (F/2.96 P) + 1. (Rb/Kr = activity ratio between 81Rb and 81mKr in the myocardium; F = myocardial perfusion (ml/min/g); P = partition coefficient (myocardium/perfusate) for Krypton gas). The constant P was found to be 1.14 +/- 0.06 (mean +/- SEM). No saturation of this ratio at high flow rates was observed. CONCLUSION: The activity ratio 81Rb/81mKr is a valid quantitative measure for myocardial perfusion in isolated hearts. The main limitation of the method before application in man is the correction of the different gamma ray tissue absorption of both nuclides.

Cineradiography for determination of normal and abnormal function in mechanical heart valves.

To determine the diagnostic value of cineradiography of mechanical heart valves, 112 cinefluoroscopic studies were performed in 76 patients with 95 valve prostheses (caged ball or disk valves, tilting disk and bileaflet valves). A patient group (n = 45) presenting with clinical or echocardiographic findings suggestive of valve-related complications was compared with a control group (n = 31) without such symptoms. Disk-opening angles (mean +/- SD) for Medtronic Hall aortic valves were found to be significantly smaller (62.8 +/- 11.1 degrees) in patients than in control subjects (73.9 +/- 1.6 degrees; p < 0.05). Tissue ingrowth or thrombus formation, or both, demonstrated in 3 patients on subsequent reoperation, are considered as the main cause of incomplete or asymmetric disk opening. Opening and closing times did not differ significantly between patients and control subjects. Besides abnormal valve motion, structural defects such as strut fracture or leaflet escape could be rapidly detected by cineradiography if x-ray projections according to the particular valve design were used. Together with quantitative Doppler echocardiographic and clinical data, this method can help to give specific answers if the question is to either confirm or exclude imminent or acute valve malfunction. Thus, modern cineradiography is a highly valuable noninvasive diagnostic tool for both rapid management of emergency cases and routine follow-up of patients with mechanical heart valves.

[Third replacement of the tricuspid valve in combined aortic-tricuspid defect]. / Trikuspidalklappen-Drittersatz bei kombiniertem Aorten-Trikuspidal-Vitium.

The implantation of valvular prostheses in tricuspid position is problematic due to the slow blood flow in the low-pressure system with the risk of valvular thromboses. Today there are prostheses with supportable low transvalvular gradients; nevertheless, the risk of valvular thromboses is, in spite of anticoagulation, increased by using mechanical prostheses in tricuspid position. We report on a 51-year-old woman in whom a dysfunction of the Starr Edwards ball prosthesis 15 years after its implantation in the tricuspid position was diagnosed. The prosthesis, which was unable to function due to connective tissue proliferation, was replaced by a St. Jude Medical prosthetic valve, which also presented a disturbed function a few days after the implantation. Because of a suspected valve thrombosis the patient was treated with rt-PA-lysis which proved to be ineffective. Thus it was inevitable to implant a third tricuspid valve; this time a bioprosthesis was used.

[Nuclear medicine assessment of renal function in beagles before and after extracorporeal percutaneous lithotripsy with a piezoelectric instrument system]. / Nuklearmedizinische Nierenfunktionsprüfung an Beagle-Hunden vor und nach extrakorporaler perkutaner Lithotripsie mit einem piezoelektrischen Gerätesystem (EPL).

High energy sound pulses which are generated piezoelectrically can be used for extracorporal lithotripsy as an alternative to shock-waves. Since several years a lithotripter for renal concrements based on piezoelectrical oscillators has been developed at the Department for Urology in Homburg/Saar; W.Germany. The present paper describes animal experiments which have been carried out with Beagle-dogs in order to prove that the sound pulses used for lithotripsy do not affect renal function. This function is measured by methods of nuclear medicine (131J-Hippuran Clearance with a modified evaluation). In addition it is evaluated by 111In labelled leucocytes if inflammatory processes in the kidney are suspected. It could be demonstrated that no detremental effects on the kidneys can be detected even with the most sensitive methods of nuclear medicine.

[Disintegration of kidney calculi by piezoelectrically generated high-energy sound waves. Physical principles and experimental studies]. / Die Zertrümmerung von Nierensteinen durch piezoelektrisch erzeugte Hochenergie-Schallpulse. Physikalische Grundlagen und experimentelle Untersuchungen.

The recently developed equipment for extracorporeal piezoelectric lithotripsy (EPL) represents an improvement concerning the shock-wave-induced disintegration of urinary calculi. While the usual spark gap transmitter needs a focusing reflector, the piezoelectric lithotriptor is based on a self-focusing spherical bowl transmitter. The stone is detected exclusively by ultrasound. For this purpose, an integrated sector scanner is used as well as the high-energy sound transmitter itself. With the piezoelectrically generated high-energy sound pulses we have succeeded in completely disintegrating implanted stones in the renal pelvis of dogs without injuring the morphology or function of the exposed kidneys.

A new method of preparing monocyte suspensions from human whole blood.

A method of isolating monocytes from human whole blood is described. The technique is primarily based on simple centrifugation steps that follow Tylose-sedimentation as well as on the use of the new density gradient medium Nycodens. Counterflow centrifugation is not involved. The final monocyte suspension is free of platelets. The contaminating cells are predominantly lymphocytes. As a whole, the method is a modification of the Nycodens technique published by Boyum in 1983, which leads to a total elimination of platelet contamination in the final cell suspension.