A noninvasive algorithm to exclude pre-capillary pulmonary hypertension.

Current guidelines recommend right heart catheterisation (RHC) in symptomatic patients at risk of pre-capillary pulmonary hypertension (PH) with echocardiographic systolic pulmonary artery pressures ≥ 36 mmHg. Growing awareness for PH, a high prevalence of post-capillary PH and the inability to distinguish between pre- and post-capillary PH by echocardiography have led to unnecessary RHCs. The aim of our study was to assess whether standard noninvasive diagnostic procedures are able to safely exclude pre-capillary PH. Data from 251 patients referred for suspicion of pre-capillary PH were used to develop a noninvasive diagnostic decision tree. A prospectively collected data set of 121 consecutive patients was utilised for temporal validation. According to the decision tree, patients were stratified by the presence or absence of an electrocardiographic right ventricular strain pattern (RVS) and serum N-terminal brain natriuretic peptide (NT-proBNP) levels below and above 80 pg·mL⁻¹. In the absence of RVS and elevated NT-proBNP, none of the patients in the prospective validation cohort were diagnosed with pre-capillary PH by RHC. Combining echocardiography with the diagnostic algorithm increased specificity to 19.3% (p = 0.0009), while sensitivity remained at 100%. Employing ECG and NT-proBNP on top of echocardiography helps recognise one false positive case per five patients referred with dyspnoea and echocardiographic suspicion of PH, while not missing true pre-capillary PH.

Inhomogeneous vasomotor effects of moderate selective and non-selective endothelin-receptor blockade in stable coronary artery disease.

OBJECTIVE: To explore the morphological and functional effect of selective and non-selective endothelin (ET)-receptor blockade in coronary artery disease (CAD). DESIGN: Prospective randomised controlled trial. SETTING: University hospital. PATIENTS: 26 patients with stable CAD. INTERVENTIONS: Intracoronary infusion (30 minutes) of the ET-A receptor blocker BQ-123 (40 nmol/min, group A, n = 13) alone or with the ET-B receptor blocker BQ-788 (10 nmol/min, group AB, n = 13) as well. MAIN OUTCOME MEASURES: Fractional flow reserve (FFR), coronary flow reserve (CFR) and intramyocardial resistance (IMR) by PressureWire, mean arterial blood pressure (MAP), minimal lumen diameter (MLD) and average angiographic lumen diameter (mean LD) of the target vessel before and after intracoronary infusion of ET antagonists. Concentrations of C-terminal pro-endothelin-1 (CT-proET1) in arterial blood were determined before and after infusion. RESULTS: Mean MLD, mean LD, FFR, CFR, IMR and MAP remained unaffected by ET-receptor blockade in both groups; their changes were comparable. Concentrations of CT-proET-1 increased by 6.2 (SD 5.9) pmol/l (95% CI 1.2 to 11.1 pmol/l; p = 0.022) in group A and by 4.1 (SD 4.3) pmol/l (95% CI 1.1 to 7.2 pmol/l; p = 0.014) in group AB. CONCLUSIONS: We found a broad variety of individual haemodynamic responses to ET-receptor antagonists with an overall neutral effect after an infusion period of 30 minutes despite an overall effective blockade of ET-receptors. Prolonged infusion time may be needed to cause a more distinct vasomotor response. TRIAL REGISTRATION NUMBER: NCT00427232.

Quantification of dose perturbation by plaque in vascular brachytherapy.

BACKGROUND: Dose prescription and reporting in vascular brachytherapy (VBT) is based on the assumption that the vessel wall is water equivalent, which does not consider a possible dose perturbation by plaque. As the extent of this perturbation is unknown, we aimed to quantify dose attenuation by atherosclerotic plaque for beta- and gamma-radiation. MATERIAL AND METHODS: The dose delivered from Strontium-90/Yttrium-90 ((90)Sr/Y) and Iridium-192 ((192)Ir) sources with and without human peripheral arteries ((90)Sr/Y: n = 38, (192)Ir: n = 7) surrounding the respective delivery catheter was determined with radiochromic films. Plaque and vessel wall thickness were measured using light microscopy. From the ratio-attenuated doseunattenuated dose (dose perturbation factor: DPF) we determined averaged attenuation coefficients for atherosclerotic plaque (micro(P)) and the residual part of the vessel wall (micro(W)) by regression analysis based on the function DPF = exp(-micro(P) * plaque thickness -micro(W) * residual wall thickness). RESULTS: Attenuation in case of (192)Ir was less than the measurement uncertainties. For beta-radiation correlation was found by discrimination between calcified and noncalcified plaque. Classifying noncalcified plaque as normal arterial tissue, the regression coefficient was r = 0.845 at micro(P)= 0.5356 mm(-1) and micro(W) = 0.0663 mm(-1). CONCLUSIONS: Vascular brachytherapy with beta radiation in calcified arteries results in significant dose attenuation within the vessel wall, which can be calculated on knowing the vascular morphometry. Thus, plaque thickness should be taken into account in treatment planning and retrospective analyses.

Percutaneous interventions in radiation-associated coronary in-stent restenosis.

This study was performed to evaluate the outcome of percutaneous revascularization in "edge restenoses" developing after radioactive stent implantation in de novo and in-stent lesions. Twenty-one consecutive patients undergoing target lesion revascularization (TLR) at any follow-up after phosphorus-32 radioactive stent implantation were included in this study. We assessed the incidence of death, myocardial infarction, repeated TLR and recurrent angina over the following 18 months. After 6 months, TLR rate was 28.6%, and no stent thromboses, deaths or Q-wave myocardial infarctions occurred. Among the patients with TLR there were significantly more subjects who had received a radioactive stent in a previous in-stent restenosis (66.7% vs. 0% in patients without second restenosis; P <0.001), or who had received two radioactive stents (83.3% vs. 33.3%; P = 0.038). After 18 months, TLR rate was 33.3%, and two patients (9.5%) had died. Restenosis after intravascular radiotherapy can be safely treated by percutaneous interventional techniques, yielding an acceptable clinical result within 18 months.

Increased intimal apoptosis in coronary atherosclerotic vessel segments lacking compensatory enlargement.

OBJECTIVES: In a histopathologic study, we assessed the balance of cell proliferation and apoptosis by counting the number of apoptotic and proliferating cell nuclear antigen-positive cells in freshly harvested atherectomy specimens from 34 patients. BACKGROUND: Remodeling of human coronary arteries is an adaptive process that alters vascular lumen size. METHODS: Intravascular ultrasound was performed prior to atherectomy. Total vessel area (area within the external elastic lamina [EEL]), lumen area and plaque area were measured at the region of interest (ROI), and at a proximal and distal reference segment, utilizing the formula Delta(%)=100x(ROI-reference segment)/reference segment. Positive arterial remodeling (R+) resulting in luminal expansion was defined as DeltaEEL >10%. Absence of remodeling (0 < DeltaEEL <10%) and constrictive arterial remodeling (DeltaEEL <0) were considered as neutral remodeling (R0) and negative remodeling (R-), respectively. RESULTS: In R- lesions, apoptotic indices (APO) were significantly elevated (17.17 +/- 2.19%) compared with R+ lesions (4.89 +/- 1.7%; p = 0.0007). In a rabbit iliac percutaneous transluminal coronary angioplasty model intimal apoptosis was increased four weeks after balloon angioplasty injury (APO 8.8 +/- 0.03%) compared with contralateral untreated segments (APO 3.0 +/- 0.04%, n = 6). Lesions with an EEL/intimal area <3.0 showed significantly more intimal apoptosis than untreated lesions (p = 0.02). CONCLUSIONS: The data indicate that constrictive remodeling of atherosclerotic coronary lesions is associated with increased apoptosis of intimal cells. We speculate that increased apoptosis is due to extensive plaque healing after episodes of symptomatic or asymptomatic plaque rupture.

An iatrogenic coronary arteriovenous fistula causing a steal phenomenon: an intracoronary Doppler study.

We present the case of a 67-year-old man in whom a guidewire broke at rotablation of the right coronary artery, creating an iatrogenic aneurysmal arteriovenous fistula to the coronary sinus. Successful Doppler wire-guided fistula occlusion by percutaneous coil embolization lead to normalization of coronary blood flow and relief of the patient's symptoms. Myocardial ischemia in this patient may have been due to a steal phenomenon caused by coronary artery fistulae, as suggested by blood flow velocity data obtained before and after fistula occlusion.

Fatal late coronary thrombosis after implantation of a radioactive stent: postmortem angiographic and histologic findings--case report.

Postmortem angiography and histologic analysis of a fatal coronary thrombosis 4 months after implantation of a radioactive stent are described. Histologic findings suggested incomplete re-endothelialization in the segment with the stent. Ionizing radiation may delay re-endothelialization after revascularization, thus maintaining the thrombogenicity of the irradiated vessel segment. Thus, prolonged antiplatelet therapy should be considered after intravascular radiation therapy.

Adaptive remodeling of the infarct-related artery is associated with recurrent ischemic events after thrombolysis in acute myocardial infarction.

BACKGROUND: Recurrent ischemic events occur during the hospital stay of 7-32% of patients after successful thrombolytic treatment of acute myocardial infarction (AMI). OBJECTIVE: To define the association between postinfarction angina pectoris and the clinical, angiographic, and intravascular ultrasound (IVUS) parameters of the infarct-related artery for consecutive prospectively included patients. METHODS: Clinical, qualitative, and quantitative angiographic and IVUS data for 64 patients (56 men, aged 53+/-12 years) with thrombolysis of AMI were analyzed. All patients underwent coronary angiography and pre-interventional IVUS measurement electively within 1 month of AMI or at the time of the occurrence of postinfarction angina pectoris. Classification as adaptive or constrictive remodeling was according to whether the cross-sectional area of a vessel was larger or smaller than that of the proximal or distal reference segment. RESULTS: Nineteen of the 64 patients (29.7%) suffered from recurrence of ischemic events (group 1), whereas 45 patients (60.3%, group 2) remained free from symptoms. In univariate analyses, multivessel disease (42 versus 24%, P= 0.0236) and adaptive remodeling (63 versus 24%, P= 0.0032) were found to occur more commonly among patients in group 1. The patients in group 1 exhibited larger total vessel cross-sectional areas than did the patients in group 2 (17.5+/-4.2 versus 14.9+/-6.1 mm2, P = 0.0556). In multivariate regression analysis, adaptive remodeling proved to be a significant predictor (P = 0.0145) of the recurrence of ischemic events after thrombolysis of AMI. CONCLUSIONS: Adaptive remodeling of the infarct-related artery is associated with early postinfarction angina pectoris after thrombolysis of AMI.

Dose-volume histograms based on serial intravascular ultrasound: a calculation model for radioactive stents.

BACKGROUND AND PURPOSE: Radioactive stents are under investigation for reduction of coronary restenosis. However, the actual dose delivered to specific parts of the coronary artery wall based on the individual vessel anatomy has not been determined so far. Dose-volume histograms (DVHs) permit an estimation of the actual dose absorbed by the target volume. We present a method to calculate DVHs based on intravascular ultrasound (IVUS) measurements to determine the dose distribution within the vessel wall. MATERIALS AND METHODS: Ten patients were studied by intravascular ultrasound after radioactive stenting (BX Stent, P-32, 15-mm length) to obtain tomographic cross-sections of the treated segments. We developed a computer algorithm using the actual dose distribution of the stent to calculate differential and cumulative DVHs. The minimal target dose, the mean target dose, the minimal doses delivered to 10 and 90% of the adventitia (DV10, DV90), and the percentage of volume receiving a reference dose at 0.5 mm from the stent surface cumulated over 28 days were derived from the DVH plots. Results were expressed as mean+/-SD. RESULTS: The mean activity of the stents was 438+/-140 kBq at implantation. The mean reference dose was 111+/-35 Gy, whereas the calculated mean target dose within the adventitia along the stent was 68+/-20 Gy. On average, DV90 and DV10 were 33+/-9 Gy and 117+/-41 Gy, respectively. Expanding the target volume to include 2.5-mm-long segments at the proximal and distal ends of the stent, the calculated mean target dose decreased to 55+/-17 Gy, and DV 90 and DV 10 were 6.4+/-2.4 Gy and 107+/-36 Gy, respectively. CONCLUSIONS: The assessment of DVHs seems in principle to be a valuable tool for both prospective and retrospective analysis of dose-distribution of radioactive stents. It may provide the basis to adapt treatment planning in coronary brachytherapy to the common standards of radiotherapy.

Directional coronary atherectomy: the Vienna experience.

BACKGROUND: Several multicenter trials have shown excellent results for directional coronary atherectomy (DCA) in a selected patient cohort. To prove the applicability of this method in daily clinical routine and a nonselected patient cohort, we analyzed 46 consecutive cases performed at our catheterization lab. METHODS: DCA was performed as a routine procedure in 45 suitable patients. Balloon dilatation or stent implantation postprocedure was accomplished only in case of unsatisfactory results. Quantitative coronary angiography was achieved pre- and postprocedure as well as at 6-month follow-up. RESULTS: Optimal atherectomy < 20% residual stenosis was reached in 24 (52%) of 46 target lesions and a residual stenosis < 50% in 46 (100%) lesions. Procedure-related complications occurred in three (6%) patients (one major complication, death, < 24 hours, 2%; two minor complications, pseudoaneurysm, 4%). The 6-month angiographic follow-up revealed a binary restenosis rate of 29% (n = 11). Ten out of 11 restenotic lesions required revascularization. When patients were stratified in two groups according to their preprocedural minimal lumen diameter (MLD), this parameter proved to be a very strong predictor of outcome. The percentage of restenosis was significantly higher in patients with an MLD > 1.60 mm compared to patients with a smaller MLD (54% vs 19.3%; P < 0.0001). Reference vessel diameter preprocedure did not differ significantly. CONCLUSIONS: Our study demonstrated that DCA is a suitable technique for the daily clinical routine, as the rates of complications and restenosis were similar to that in a highly selective patient cohort. Additionally, our study showed that patient selection should include preprocedural analysis of MLD in order to achieve optimal results. Therefore, atherectomy yielded comparable results to other conventional techniques and may be used instead of or in combination with them.

Successful emergency percutaneous cardiopulmonary support during coronary intervention in an 80-year old patient.

In an 80-year old patient with acute coronary syndrome emergency institution of stand-by percutaneous cardiopulmonary support (PCPS; Bio-Medicus; Medtronic Inc, Minneapolis MN) for hemodynamic collapse in the cardiac catheterization laboratory resulted in successful hemodynamic stabilization and enabled safe performance of a complex coronary intervention. Weaning from PCPS was effectuated after 4 hours total extracorporal circulation time. Despite development of a systemic inflammatory response syndrome and prolonged weaning from mechanical ventilation the patient could be discharged from the intensive care unit after 14 days and eventually from hospital another 28 days later with favorable outcome. Although an increased complication rate with prolonged rehabilitation has to be taken into account percutaneous cardiopulmonary support may constitute a live-saving option even in selected elderly patients.

Pre-existing arterial remodeling is associated with in-hospital and late adverse cardiac events after coronary interventions in patients with stable angina pectoris.

OBJECTIVES: The goal of this study was to investigate the association between the atherosclerotic arterial remodeling and the incidence of cardiac events after coronary interventions in patients with stable angina. BACKGROUND: The local mode of de novo atherosclerotic remodeling is associated with plaque vulnerability and clinical symptoms. It may, therefore, reflect plaque morphology influencing the long-term outcome after coronary interventions. METHODS: Quantitative angiography and intravascular ultrasound were obtained in 244 patients with stable angina before and after single-vessel revascularization. On the basis of the lesion and the reference segment vessel size, patients were categorized into three groups (adaptive [AR], constrictive [CR] and intermediate [IR] remodeling). The lesion was analyzed for lumen, total vessel and plaque areas. Clinical follow-up was obtained at a mean period of 7.7+/-3.7 months. RESULTS: Patients with CR had a higher rate of in-hospital complications (10.9% vs. 2.9% and 2.7% in group CR vs. AR and IR, p = 0.035). In contrast, patients with AR had the highest rate of major adverse cardiac events (MACE) (44.3% vs. 25.5% in IR and 28.1% in CR, p = 0.024) with a predominance of revascularization at follow-up. Both target lesion restenosis (p = 0.036) and nontarget lesion de novo stenosis (p = 0.007) occurred more frequently in this group. Adaptive remodeling was a significant predictor of MACE in multivariate analysis. CONCLUSIONS: Adaptive remodeling is associated with a higher rate of MACE, target lesion restenosis and nontarget de novo stenosis. This finding may be due to differential responses of the adaptively remodeled vessel to revascularization and a generally accelerated course of systemic atherosclerosis.

Plasma levels of C-reactive protein after coronary stent implantation.

AIMS: This study was designed to investigate the role of inflammation on the occurrence of angiographic restenosis 6 months after coronary stent implantation and the influence of different kinds of antithrombotic and antiplatelet strategies on inflammation. METHODS AND RESULTS: In an open randomized trial, 40 consecutive patients were treated with aspirin (100 mg. day(-1)) and either ticlopidine (2x250 mg. day(-1)) (n=17), or phenprocoumon (INR 2.0-3.0) and dipyridamole (3x160 mg. day(-1)) (n=23) after successful elective coronary stent implantation. Plasma levels of C-reactive protein were determined one day before stent implantation and serially thereafter twice daily up to 120 h. C-reactive protein plasma levels increased significantly (P<0.0001) after stent implantation. Phenprocoumon and dipyridamole or ticlopidine had no effect on C-reactive protein plasma levels (P=0.51) or the occurrence of angiographic restenosis (P=0.48). C-reactive protein plasma levels were significantly higher in patients with lesion type C compared to types A or B (P=0.035), respectively. C-reactive protein plasma levels were significantly higher and mean shoulder levels occurred 48 h later in patients with restenosis compared to patients without restenosis after 6 months (P=0.038). CONCLUSIONS: Elevated C-reactive protein plasma levels still persisting 96 h after stent implantation might reflect a prolonged inflammatory reaction to coronary stent implantation which might causally be involved in pathophysiological mechanisms leading to restenosis.

Design and dosimetry of a novel 90Y beta source to prevent restenosis after angioplasty.

PURPOSE: Post-dilatation irradiation of the vessel wall is currently under investigation for prevention of restenosis after balloon dilatation. For the irradiation, special sources were designed for animal experiments which would give equivalent irradiation conditions and doses to the vessel wall that would later be employed for human application. METHODS AND MATERIALS: For the planned irradiations, a specially designed yttrium-wire of 0.45-mm diameter coated with a thin shrink tube to prevent contamination was deployed. Several leakage tests applied before and after application proved that the irradiation source was leakproof. Dosimetry was performed by using 0.1-mm-thick thermoluminescent dosimeters (TLD-100) calibrated against a primary standard. A shielding transport and application container was designed to facilitate the handling of the source during use, while reducing exposure of the medical personnel. RESULTS: The designed source proves to be flexible for the insertion into proximal coronary vessels, and positioning at the site of stenosis. It provides an optimum protection of the animal and requires little radiation protection efforts on behalf of the medical staff. Dosimetric calculations and measurements showed that a centering of the source inside the vessel could be achieved with a maximum deviation of 50% between maximum and average dose levels. CONCLUSION: A yttrium-90 beta brachytherapy source was designed which provides high flexibility within proximal coronary arteries, ensures an adequate centering inside the artery, and provides irradiation conditions to the vessel wall of the experimental animal comparable to the application inside a human artery.