I. De Scheerder

Intravascular ultrasound versus angiography for measurement of luminal diameters in normal and diseased coronary arteries

Quantitation of coronary luminal diameter with a 20 MHz mechanically rotating intravascular ultrasound (IVUS) catheter was compared with orthogonal-view cineangiography by use of a semiautomated edge-detection algorithm in 48 patients undergoing coronary angioplasty. Quantitative comparison of 196 matched segments was attempted, but in only 174 (88.8%) was a direct comparison of the two techniques possible. In angiographically normal coronary arteries (46 segments) the correlation between the values obtained by quantitative coronary angiography (QCA) and those achieved by IVUS was excellent (r = 0.92, p < 0.0001). For mild stenoses (80 segments) the correlation coefficient was only fair (r = 0.467, p < 0.001). After percutaneous transluminal coronary angioplasty the correlation coefficient between IVUS and QCA data (48 segments) was very weak (r = 0.282, p < 0.05). In conclusion, coronary IVUS is feasible and safe and even for a limited range of coronary arterial narrowing, significant correlations between IVUS and QCA measurements of minimal lumen diameter were found. They were excellent in normal coronary arteries, moderate in mildly diseased arteries, and weak after balloon angioplasty.

Relative risk analysis of angiographic predictors of restenosis within the coronary Wallstent.

BackgroundLate angiographic narrowing has been observed following coronary implantation of the Wallstent®. To identify the angiographic variables that predict restenosis within the stented segment, a retrospective study of data from the European Wallstent core laboratory was performed. Methods and ResultsFollow-up angiograms (excluding patients with in-hospital occlusions) were analyzed for 214 lesions in 176 patients (78% restudy rate). The incidence of restenosis within the stented segment was 35% by lesion and 35% by patient for criterion 1 (20.72 mm loss in minimal luminal diameter) and 24% by lesion and 24% by patient for criterion 2 (diameter stenosis 50% at follow-up). The association between 16 variables and restenosis was determined by a relative risk ratio assessment. Variables with significant risk ratios for restenosis with criterion 1 were use of multiple stents/lesion (relative risk, 1.56; 95% confidence interval [CI], 1.08–2.25) and oversized (unconstrained stent diameter exceeding reference diameter > 0.7 mm) stents (relative risk, 1.64; 95% CI, 1.10–2.45), and for criterion 2, oversizing by more than 0.70 mm (relative risk, 1.93; 95% CI, 1.13–3.31), bypass grafts (relative risk, 1.62; 95% CI, 0.98–2.66), use of multiple stents/lesion (relative risk, 1.61; 95% CI, 0.97–2.67) and residual diameter stenosis more than 20% post stenting (relative risk, 1.51; 95% CI, 0.91–2.50). ConclusionsIt is concluded that several angiographic variables are significantly associated with late angiographic narrowing after stenting in the coronary arteries. We suggest that stent operators avoid excessive oversizing in the selection of stent diameter and the use of multiple stents per lesion to lessen the risk of late restenosis.

M cells and transmural heterogeneity of action potential configuration in myocytes from the left ventricular wall of the pig heart

OBJECTIVEnHeterogeneity of action potential configuration in the left ventricle (LV), and the contribution of M cells to it, has been observed in the human heart and is important for arrhythmogenesis. Whether the pig heart has similar properties remains a controversial but important issue as the pig heart is currently under study for use in xenotransplantation.nnnMETHODSnSingle myocytes were enzymatically isolated from the epicardium (EPI, ncells = 29), midmyocardium (MID, ncells = 38), and endocardium (ENDO, ncells = 13) of the free LV wall (npigs = 26, 14-22 weeks old, 55-80 kg), and studied at different stimulation rates during whole-cell recording (normal Tyrodes solution, K(+)-aspartate-based pipette solution, 50 microM K5fluo-3 as [Ca2+]i indicator, 37 degrees C). Standard six-lead ECGs were recorded from anesthetized pigs.nnnRESULTSnThe action potential duration (APD) was not significantly different at 0.25 Hz vs. 2 Hz for the majority of cells in all three layers. However, a subpopulation of cells behaved like M cells and had a very steep frequency response (APD90 at 0.25 Hz 538 +/- 30 ms, vs. 337 +/- 9 ms at 2 Hz, P < 0.05, n = 22). These cells were found predominantly in the MID layer (34% of cells), but also (24%) in EPI. M cells had a more pronounced spike-and-dome configuration, with a significantly larger phase 1 magnitude and plateau voltage. The frequency response of these parameters was different from the other cell types. [Ca2+]i transients tended to be larger in M cells. For the in vivo ECG of anesthetized pigs, the QT time was close to the APD90 of M cells, and J waves were seen in 7/12 recordings.nnnCONCLUSIONSnIn young adult pigs, M cells can be identified by a steep frequency response of the APD and by a spike-and-dome configuration. These cells are mostly, but not exclusively, found in the midmyocardium, and could contribute to the ECG characteristics. Their properties may however be different from those of other species, including humans.

Angiotensin-converting enzyme inhibition with fosinopril sodium in the prevention of restenosis after coronary angioplasty.

BACKGROUNDnSeveral angiotensin-converting enzyme inhibitors have antiproliferative effects in a rat model after carotid artery balloon injury.nnnMETHODS AND RESULTSnWe conducted a randomized, double-blind, placebo-controlled trial to assess the effect of fosinopril, a novel angiotensin-converting enzyme inhibitor, in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received fosinopril or matched placebo 10 mg at least 18 hours before PTCA, 20 mg at least 4 hours before PTCA, and 40 mg daily for 6 months. In addition, all patients received aspirin. Coronary angiograms before PTCA and immediately after PTCA as well as at 6-month follow-up were quantitatively analyzed. A total of 509 patients were recruited. The final per-protocol population consisted of 153 fosinopril-treated and 151 placebo-treated patients. Restenosis rates according to the National Heart, Lung, and Blood Institute criterion 4 (loss of > or = 50% of the initial gain [primary end point]) were 45.7% and 40.7% in the fosinopril and control groups, respectively (not significant). The respective mean differences in minimal coronary luminal diameter between post-PTCA and follow-up angiograms were -0.59 +/- 0.71 mm and -0.51 +/- 0.67 mm (not significant). Clinical events during the 6-month follow-up period, analyzed on an on-treatment basis, were ranked according to the most serious event. The respective numbers in the fosinopril and the control groups were for death, 0 and 0; myocardial infarction, 0 and 0; coronary artery bypass graft surgery, 1 and 3; repeat PTCA, 35 and 35; recurrent signs of ischemia necessitating early repeat coronary angiography and managed medically, 6 and 7; and none of the above, 111 and 106. All these differences were significant.nnnCONCLUSIONSnAdministration of fosinopril in a dose of 40 mg daily during 6 months after PTCA does not prevent restenosis and has no effect on overall clinical outcome.

Long term effects of nisoldipine on the progression of coronary atherosclerosis and the occurrence of clinical events: the NICOLE study

Background: Earlier angiographic studies have suggested that calcium antagonists may prevent the formation of new coronary lesions and the progression of minimal lesions. Conversely, a meta-analysis suggested that these drugs may increase cardiovascular mortality and morbidity in patients with coronary heart disease. Objective: To investigate whether nisoldipine retards the progression of coronary atherosclerosis or reduces the occurrence of clinical events. Design and setting: The NICOLE study (NIsoldipine in COronary artery disease in LEuven) is a single centre, randomised, double blind, placebo controlled trial with coronary angiography at baseline, six months, and three years of follow up. Patients: 826 patients who had undergone successful coronary angioplasty were randomised to nisoldipine 40 mg once daily or placebo. The intention to treat and per protocol population consisted of 819 and 578 patients, respectively. Results: In the per protocol population, 625 of the nisoldipine treated and 655 of the placebo treated patients (NS) showed angiographic progression in at least one coronary arterial segment, defined as an increase in diameter stenosis of ≥ 13%. The average minimum luminal diameter of the non-dilated lesions decreased by 0.163 mm and 0.167 mm in the nisoldipine and placebo groups, respectively (NS). The respective numbers of new lesions detected were 7 and 13 (NS). In the intention to treat population, the rates of death, stroke, and acute myocardial infarction were similar in both treatment groups. However, nisoldipine use was associated with fewer revascularisation procedures and thus the percentage of patients with any clinical event was lower (44.6% v 52.6%, p = 0.02). Conclusions: Nisoldipine has no demonstrable effect on the angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but its use is associated with fewer revascularisation procedures.

Postoperative immunological response against contractile proteins after coronary bypass surgery.

The pathogenesis of post-cardiac injury syndrome was studied prospectively in 62 patients who underwent coronary bypass grafting. Preoperative and serial postoperative titres of actin and myosin antibodies were measured by an enzyme linked immunosorbent assay. Perioperative cumulative release of serum aspartate and alanine aminotransferases, lactate dehydrogenase, and creatine kinase was calculated by approximation formulas that are used to estimate infarct size. Complete post-cardiac injury syndrome developed in eight (13%) patients and an incomplete syndrome developed in 16 (26%). There was a significant correlation between frequency and intensity of the syndrome and the ratio of postoperative to preoperative titres of actin and myosin antibodies. Furthermore, there was a significant correlation between the cumulative release of lactate dehydrogenase, serum aspartate aminotransferase, and creatine kinase and the number of coronary vessels that were grafted, but no correlation was found between the incidence of post-cardiac injury syndrome and the number of coronary bypasses grafted or between the cumulative enzyme release and the postoperative immunological response against the major contractile proteins, actin and myosin. The amount of enzymes released during coronary bypass surgery seems to be a good indicator of the extent of myocardial damage during operation but it does not determine either the incidence of post-cardiac injury syndrome or the postoperative immunological response against the main contractile proteins actin and myosin.

Methotrexate loaded SAE coated coronary stents reduce neointimal hyperplasia in a porcine coronary model

Objective: To evaluate the effect of stent based methotrexate delivery on neointimal hyperplasia. Methods: Stainless steel coronary stents and biological polymer coated (SAE) stents were randomly implanted in coronary arteries of pigs with a stent to artery ratio of 1.1:1. The pigs were killed after five days (10 stents) or four weeks (20 stents). Second, stainless steel coronary stents were dip coated in a 10 mg/ml methotrexate–SAE polymer solution, resulting in a total load of 150 μg methotrexate/stent. SAE coated stents and methotrexate loaded stents were randomly implanted in porcine coronary arteries with a stent to artery ratio of 1.2:1 and followed up to four weeks. Results: SAE coated stents and bare stents elicited a similar tissue response at five days. At four weeks, neointimal hyperplasia induced by the coated stents was less pronounced than with the bare stents (1.32 (0.66) v 1.73 (0.93) mm2, p > 0.05). In vitro drug release studies showed that 50% of the methotrexate was released in 24 hours, and all drug was released within four weeks. No impact on vascular smooth muscle cell proliferation or viability was observed in in vitro cell cultures. At four weeks the arteries with methotrexate loaded stents had decreased peristrut inflammation and neointimal hyperplasia (1.22 (0.34) v 2.25 (1.28) mm2, p < 0.01). Conclusions: SAE coating had an excellent biocompatibility with vascular tissue. Stent based delivery of methotrexate in the SAE coating effectively reduced neointimal hyperplasia in a porcine coronary stent model, potentially due to reduced peristrut inflammation.

Macro CK type 1 as a marker for autoimmunity in coronary heart disease

In a group of 3000 hospital patients the prevalence of immunoglobulin bound creatine kinase (macro CK type 1) was 4.3%. The relative frequency was greater in the older age categories. The highest prevalence was found in patients with rheumatic and cardiac diseases. In a group of 556 cardiac patients selected for coronary angiography a prevalence of 13.8% was observed. No significant correlation was obtained between the findings of the coronary angiography and the activity of macro CK type 1. CK MB results determined by ion-exchange or immuno-inhibition techniques in macro CK type 1 positive patients are falsely positive. Macro CK type 1 may be seen as an antigen-antibody complex against CK BB, which originates at least partly from the vascular wall.

Biocompatibility of coronary stent materials : Effect of electrochemical polishing

Percutaneous Transluminal Coronary Revascularization (PTCR) is now a widely accepted treatment modality for atherosclerotic coronary artery disease. n n n nCurrent multicenter randomized trials comparing PTCR with the more invasive Coronary Artery Bypass Grafting could not show long-term significant survival differences. n n n nDuring the last two decades progress has been made to further optimize PTCR. The most logic approach to treat atherosclerotic coronary narrowings is to remove the atherosclerotic material using especially developed devices. Several trials, however, could not show a significant beneficial outcome after use of these devices compared to plain old balloon angioplasty. n n n nAnother approach was to implant a coronary prothesis (stent), scaffolding the diseased coronary artery after PTCA. This approach resulted in a decreased restenosis rate at follow-up. The beneficial effects of stenting, however, was not found to be related to the inhibition of the neointimal cellular proliferation after vascular injury, but simply to be the mechanical result of overstretching of the treated vessel segment. n n n nThe most important remaining clinical problem after stenting remains the neointimal hyperplasia within the stent, resulting in a significant stent narrowing in 13 to 30 % of patients. Further efforts to improve the clinical results of coronary stenting should focus on the reduction of this neointimal hyperplasia. n n n nNeointimal hyperplasia after stent implantation results from (1) a healing response to the injury caused by the stent implantation and (2) a foreign body response to the stent itself. Factors that seem to influence the neointimal hyperplastic response are genetic, local disease related, stent delivery related and stent related factors. n n n nBiocompatibilisation of coronary stents by looking for more biocompatible metal alloys, optimized surface characteristics and optimized stent designs should result in a better late patency. Furthermore drug eluting and radioactive stents are under development in order to decrease the neointimal hyperplastic response. n n n nBiokompatibilitat des Koronarstentmaterials: das Ergebnis des elektrochemischen Polierens n n n nPerkutane Transluminale Koronare Revaskularisierung (PTKR) ist heutzutage eine weit akzeptierte Behandlungsmodalitat koronararterieller Krankheit. n n n nHeutige randomisierte Vielzentrenstudien vergleichen PTKR und mehr intervenierende Koronararterie-Uberbruckungs-Chirurgie (KABC) miteinander. Sie konnten keine signifikanten Unterschiede zeigen. n n n nIn den letzten 10 Jahren wurden Fortschritte gemacht um PTKR weiter zu optimieren. n n n nDie logischte Weise um atherosklerotische Koronarverengungen zu behandeln, ist die Entfernung des atherosklerotischen Materials mit speziellen Hilfsmitteln. n n n nAber verschiedene Studien konnten kein signifikantes heilsames Resultat zeigen nach Gebrauch dieser Hilfsmittel im Vergleich mit der gewohnten Ballonangioplastie. n n n nEine andere Methode war die Einpflanzung einer Koronarprothese (Stent), die die kranke Koronararterie nach PTCA stutzen sollte. n n n nDiese Arbeitsweise resultierte in einem verringerten Restenosegrad bei Nachuntersuchungen. n n n nDas heilsame Ergebnis des Stents war jedoch nicht verbunden mit der Sperrung der neointimalen zellularen Vervielfaltigung nach vaskularer Verletzung, sondern war einfach das mechanische Resultat der Uberdehnung des behandelten Blutgefases. n n n nDas wichtigste klinische Problem nach dem Stenten bleibt jedoch die Hyperplasie im Stent, resultierend in einer signifikanten Verengung des Stents bei 13 bis 30 % der Patienten. n n n nWeitere Anstrengungen um die klinischen Ergebnisse koronaren Stentes zu verbessern sollten sich auf die Reduktion der neointimalen Hyperplasie konzentrieren. n n n nDie neointimale Hyperplasie nach Einpflanzung eines Stents resultiert aus (1) einer heilenden Antwort auf die Verletzungen verursacht durch die Einpflanzung eines Stents und (2) eine Fremdkorper-Antwort gegen den Stent selbst. n n n nDie Faktoren, die die neointimale Hyperplasie wahrscheinlich beeinflussen sind Faktoren, die in Verbindung stehen mit der Genetik, lokalen Krankheiten, dem Stent und der Stentplatzierung. n n n nBiokompatibilisierung des Koronarstents durch Suchen nach mehr biokompatiblen Metalllegierungen, optimierten Oberflachencharakteristiken und optimierte Stentkonzepte sollten resultieren in einem besseren spaten Patent. n n n nObendrein sind Stents die Heilmittel freilassen und radioaktive Stents in Entwicklung, damit die neointimale hyperplastische Antwort reduziert wird.

Assessment of myocardial viability in a porcine model of chronic coronary artery stenosis with dual dose dobutamine magnetic resonance imaging

In a non-surgical porcine coronary stenosis model resulting in chronic left ventricle dysfunction, we aimed in this study to evaluate the potential of magnetic resonance imaging (MRI) to distinguish dysfunctional but viable from necrotic myocardium by using multiple levels of dobutamine inotropic stimulation during a cine MRI protocol (F.P. van Rugge et al. Circulation 1994; 90: 127–138). We compared our results with histopathology. We were able to demonstrate a biphasic effect at increasing doses of dobutamine in a subgroup of animals with a high-grade coronary stenosis, while in another subgroup the coronary stenosis produced a chronic myocardial infarction, in which no functional recovery could be obtained. In this experimental protocol, dual dose dobutamine MRI proved to be an accurate and reproducible technique to perform viability studies in chronic obstructive coronary artery disease. It permits distinguishing chronic ischemic, but viable myocardium from infarcted tissue. The detection of chronically underperfused but potentially salvageable myocardium is of significant clinical importance since it may aid in determining which patients are eligible for revascularization.