A relatively simple, invasive method for quantitatively assessing the status of the coronary microcirculation independent of the epicardial artery is lacking.
By using a coronary pressure wire and ...modified software, it is possible to calculate the mean transit time of room-temperature saline injected down a coronary artery. The inverse of the hyperemic mean transit time has been shown to correlate with absolute flow. We hypothesize that distal coronary pressure divided by the inverse of the hyperemic mean transit time provides an index of microcirculatory resistance (IMR) that will correlate with true microcirculatory resistance (TMR), defined as the distal left anterior descending (LAD) pressure divided by hyperemic flow, measured with an external ultrasonic flow probe. A total of 61 measurements were made in 9 Yorkshire swine at baseline and after disruption of the coronary microcirculation, both with and without an epicardial LAD stenosis. The mean IMR (16.9+/-6.5 U to 25.9+/-14.4 U, P=0.002) and TMR (0.51+/-0.14 to 0.79+/-0.32 mm Hg x mL(-1) x min(-1), P=0.0001), as well as the % change in IMR (147+/-66%) and TMR (159+/-105%, P=NS versus IMR % change), increased significantly and to a similar degree after disruption of the microcirculation. These changes were independent of the status of the epicardial artery. There was a significant correlation between mean IMR and TMR values, as well as between the % change in IMR and % change in TMR.
Measuring IMR may provide a simple, quantitative, invasive assessment of the coronary microcirculation.
Current treatment for acute myocardial infarction (AMI) focuses on reestablishing blood flow (reperfusion). Paradoxically, reperfusion itself may cause additional injury to the heart. We previously ...found that delta-protein kinase C (deltaPKC) inhibition during simulated ischemia/reperfusion in isolated rat hearts is cardioprotective. We focus here on the role for deltaPKC during reperfusion only, using an in vivo porcine model of AMI.
An intracoronary application of a selective deltaPKC inhibitor to the heart at the time of reperfusion reduced infarct size, improved cardiac function, inhibited troponin T release, and reduced apoptosis. Using 31P NMR in isolated perfused mouse hearts, we found a faster recovery of ATP levels in hearts treated with the deltaPKC inhibitor during reperfusion only.
Reperfusion injury after cardiac ischemia is mediated, at least in part, by deltaPKC activation. This study suggests that including a deltaPKC inhibitor at reperfusion may improve the outcome for patients with AMI.
Aims To investigate whether intravascular ultrasound provides additional information regarding the prediction of stent thrombosis, a retrospective multicentre registry was designed to enrol patients ...with stent thrombosis following stent deployment under ultrasound guidance. Methods and Results A total of 53 patients were enrolled (mean age 61±9 years) with stable angina (43%), unstable angina (36%), and post-infarct angina (21%) who underwent intracoronary stenting. The majority had balloon angioplasty alone prior to stenting (94%) with 6% also undergoing rotational atherectomy. The indication for stenting was elective (53%), suboptimal result (32%) and bailout (15%). There were 1·6±0·8 stents/artery with 87% undergoing high-pressure dilatation (≥14 atmospheres). The minimum stent area was 7·7±2·8mm2with a mean stent expansion of 81·5±21·9%. Overall, 94% of cases demonstrated one abnormal ultrasound finding (stent under-expansion, malapposition, inflow/outflow disease, dissection, or thrombus). Angiography demonstrated an abnormality in only 32% of cases (chi-square=30·0,P <0·001). Stent thrombosis occurred at 132±125h after deployment. Myocardial infarction occurred in 67% and there was an overall mortality of 15%. Conclusion On comparison with angiography, the vast majority of stents associated with subsequent thrombosis have at least one abnormal feature by intravascular ultrasound at the time of stent deployment.
Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been ...thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model.
Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10(7) 111indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by gamma-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26+/-3% (IM), 47+/-1% (IC), and 43+/-3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11+/-3%) compared with IC (2.6+/-0.3%) (P<0.05) delivery. IRV delivery efficiency (3.2+/-1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques.
The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.
Thermodilution coronary flow reserve (CFRthermo) is a new technique for invasively measuring coronary flow reserve (CFR) with a coronary pressure wire and is based on the ability of the pressure ...transducer to also measure temperature changes. Whether CFRthermo correlates well enough with absolute flow-derived CFR (CFRflow) to replace Doppler wire-derived CFR (CFRDoppler) remains unclear.
In an open-chest pig model, CFRthermo was measured in the left anterior descending (LAD) artery and compared with CFRDoppler and CFRflow, measured with an external flow probe placed around the LAD. In 9 pigs, CFR was measured simultaneously by all 3 means in the normal LAD and after creation of an epicardial LAD stenosis. To determine the added effect of microvascular disease, measurements of flow reserve were also performed after disruption of the coronary microcirculation with embolized microspheres. Intracoronary papaverine (20 mg) was used to induce hyperemia. In a total of 61 paired measurements, CFRthermo correlated strongly with the reference standard CFRflow (r=0.85, P<0.001). CFRDoppler correlated less well with CFRflow (r=0.72, P<0.001). Bland-Altman analysis showed a closer agreement between CFRthermo and CFRflow.
CFRthermo correlates better with CFRflow than does CFRDoppler.
Background Conventional gray-scale images of intravascular ultrasound (IVUS) cannot accurately differentiate histologic subtypes of sonolucent coronary plaques with or without a lipid core. Methods ...We analyzed radiofrequency signals obtained in vitro from 24 regions of interest (ROI) of noncalcified (sonolucent) plaques in 10 atherosclerotic coronary artery specimens pressure-fixed by formalin. Radiofrequency signals were sampled with a 30-MHz IVUS catheter and digitized at 500 MHz in 8-bit resolution. The ROIs were histologically categorized into 12 plaques with a lipid core and 12 plaques without it. Integrated backscatter and statistical parameters of the radiofrequency envelope (mean/SD ratio MSR, skewness, and kurtosis) within the ROI were calculated offline, and their ability to detect a lipid core was compared with visual analysis of the IVUS video images. In the group with lipid cores, percent area of a lipid core in each ROI was measured in a digitized histologic image by a computerized planimeter. Results Sensitivity and specificity of MSR, skewness, and kurtosis for lipid core detection were substantially greater than visual video image analysis (83.3% and 91.7%, 100% and 91.7%, 100% and 91.7% vs 53.3% and 71.7%). Furthermore, the parameters of integrated backscatter, MSR, skewness, and kurtosis were significantly correlated to percent of core area (r = –0.64, –0.73, 0.78, and 0.63, respectively; P < .05). Conclusions Compared with IVUS video images, the parameters of radiofrequency signal analysis may be used to aid in more accurate detection and quantitative evaluation of a lipid core, which is one of the major factors of a vulnerable coronary plaque. (Am Heart J 2000;140:565-74.)
We assessed the predictive value of minimum stent area (MSA) for long-term patency of sirolimus-eluting stents (SES) implantation compared to bare metal stents (BMS).
Although MSA is a consistent ...predictor of in-stent restenosis, its predictive value in BMS is still limited because of biologic variability in the restenosis process.
From the SIRolImUS (SIRIUS) trial, 122 cases (SES: 72; BMS: 50) with complete serial intravascular ultrasound (IVUS) (baseline and 8-month follow-up) were analyzed. Postprocedure MSA and follow-up minimum lumen area (MLA) were obtained. Based on previous physiologic studies, adequate stent patency at follow-up was defined as MLA >4 mm(2).
In both groups, a significant positive correlation was observed between baseline MSA and follow-up MLA (SES: p < 0.0001, BMS: p < 0.0001). However, SES showed higher correlation than BMS (0.8 vs. 0.65) with a higher regression coefficient (0.92 vs. 0.59). The sensitivity and specificity curves identified different optimal thresholds of MSA to predict adequate follow-up MLA: 5 mm(2) for SES and 6.5 mm(2) for BMS. The positive predictive values with these cutoff points were 90% and 56%, respectively.
In this SIRIUS IVUS substudy, SES reduced both biologic variability and restenosis, resulting in increased predictability of long-term stent patency with postprocedure MSA. In addition, SES had a considerably lower optimal MSA threshold compared to BMS.
Atherosclerotic plaque fracture and dissection of the arterial wall are frequent concomitants of the balloon angioplasty process. The composition and morphology of plaque within the vessel may be ...critical in determining the extent of plaque fracture and dissection during balloon angioplasty. To examine this potential association in the clinical setting, we studied patients with intravascular ultrasound imaging after balloon angioplasty.
Forty-one patients were studied with intravascular ultrasound after angioplasty in both peripheral and coronary arteries. Ultrasound images representing the target lesion cross section were digitized, stored on computer, and analyzed off-line. The presence of intralesional calcium and the relative size of dissection for each lesion was computed. Thirty-one patients (76%) had ultrasound evidence of significant dissection or plaque fracture immediately after balloon dilation. In 23 of 31 (74%) of the lesions, the ultrasound scans showed significant localized calcium deposits within the plaque substance. In 87% of these cases, the dissections were adjacent to the calcific portion of the vessel wall. In addition, the relative size of dissections referenced to the neolumen area were significantly larger (p less than or equal to 0.002) in the calcified vessels (27.5 +/- 12.3%) compared with the size of the dissections in lesions without calcium (11.2 +/- 5.8%).
The presence of calcium within the vessel wall appeared to be significantly associated with both the location and size of the dissected tissue arm from the vessel wall. These data suggest that localized calcium deposits have a direct role in promoting dissection, presumably by increasing shear stresses within the plaque.
Background Fractional flow reserve (FFR) is a measure of coronary stenosis severity that is based on pressure measurements obtained at maximal hyperemia. The most widely used pharmacologic stimulus ...for maximal coronary hyperemia is adenosine, administered either as a continuous intravenous (IV) infusion or intracoronary (IC) bolus. IV adenosine has more side effects and is more costly than IC adenosine but has a more stable and prolonged hyperemic effect. Methods We compared the efficacy of IC and IV adenosine administration for the measurement of FFR in a multicenter trial. Fifty-two patients with 60 lesions underwent determination of FFR with both IV and IC adenosine. IV adenosine was administered as a continuous infusion at a rate of 140 μg/kg per minute until a steady state hyperemia was achieved. IC adenosine boluses were administered at a dose of 15 to 20 μg in the right and 18 to 24 μg in the left coronary artery. FFR was calculated as the ratio of the distal coronary pressure (from pressure guide wire) to the aortic pressure (guide catheter) at maximal hyperemia. Results A total of 26 left anterior descending, 23 right, 9 left circumflex, and 3 left main coronary arteries were evaluated. Mean percent stenosis for both groups was 55.8% ± 23.6% (range 0% to 95%), and mean FFR was 0.78 ± 0.15 (range 0.41 to 0.98). There was a strong and linear correlation between FFR measurements with IV and IC adenosine (R = 0.978, y = 0.032 + 0.964x, P < .001). The agreement between the 2 sets of measurements was also high, with a mean difference in FFR of –0.004 ± 0.03. However, a small random scatter in both directions of FFR measurements was noted with 5 lesions (8.3%) where FFR with IC adenosine was higher by 0.05 or more compared with IV infusions, suggesting a suboptimal hyperemic response in these patients. Changes in heart rate and blood pressure were significantly higher with IV adenosine. Two patients with IV, but none with IC adenosine, had severe side effects (bronchospasm and severe nausea). Conclusion These results suggest that IC adenosine is equivalent to IV infusion for the determination of FFR in the majority of patients. However, in a small percentage of cases, coronary hyperemia was suboptimal with IC adenosine. (Am Heart J 2000;140:651-7.)
We sought to identify the frequency of incomplete stent apposition (ISA) in sirolimus-eluting stents (SES) and clarify its findings and clinical sequelae.
Late-acquired ISA has been reported in ...bare-metal stents (BMS) and brachytherapy and recently in drug-eluting stents. However, the characteristics of late ISA in SES have not been clarified.
From the SIRIUS trial, a randomized, multicenter study comparing SES and BMS, serial qualitative intravascular ultrasound (IVUS; at stent implantation and eight-month follow-up) was available in 141 patients (BMS: n = 61; SES: n = 80). The IVUS images were reviewed for the presence of ISA.
Incomplete stent apposition at follow-up was observed in 19 patients (BMS: n = 6 9.8%; SES: n = 13 16.3%; p = NS). Among these, 12 had ISA after intervention and at follow-up (persistent ISA). Late-acquired ISA was seen in the remaining seven cases, all from the SES group (BMS: n = 0; SES: n = 7 8.7%; p < 0.05). In late-acquired ISA, there was an increase in external elastic membrane area (after intervention: 16.2 +/- 2.7 m2; follow-up: 18.9 +/- 3.6 mm2; p < 0.05). The location of stent-vessel wall separation was primarily at the stent edges in persistent ISA cases, whereas late-acquired ISA in SES occurred mostly in the mid portion of the stent. There were no negative clinical events reported for any ISA cases at 12-month clinical follow-up.
Late ISA was observed in 8.7% of patients after SES implantation. There were no negative clinical events associated with this IVUS finding at 12-month clinical follow-up; however, careful long-term follow-up will be necessary.
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