Jacques J. Koolen

Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses

BACKGROUND The clinical significance of coronary-artery stenoses of moderate severity can be difficult to determine. Myocardial fractional flow reserve (FFR) is a new index of the functional severity of coronary stenoses that is calculated from pressure measurements made during coronary arteriography. We compared this index with the results of noninvasive tests commonly used to detect myocardial ischemia, to determine the usefulness of the index. METHODS In 45 consecutive patients with moderate coronary stenosis and chest pain of uncertain origin, we performed bicycle exercise testing, thallium scintigraphy, stress echocardiography with dobutamine, and quantitative coronary arteriography and compared the results with measurements of FFR. RESULTS In all 21 patients with an FFR of less than 0.75, reversible myocardial ischemia was demonstrated unequivocally on at least one noninvasive test. After coronary angioplasty or bypass surgery was performed, all the positive test results reverted to normal. In contrast, 21 of the 24 patients with an FFR of 0.75 or higher tested negative for reversible myocardial ischemia on all the noninvasive tests. No revascularization procedures were performed in these patients, and none were required during 14 months of follow-up. The sensitivity of FFR in the identification of reversible ischemia was 88 percent, the specificity 100 percent, the positive predictive value 100 percent, the negative predictive value 88 percent, and the accuracy 93 percent. CONCLUSIONS In patients with coronary stenosis of moderate severity, FFR appears to be a useful index of the functional severity of the stenoses and the need for coronary revascularization.

Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial

BACKGROUND Coronary stents improve immediate and late results of balloon angioplasty by tacking up dissections and preventing wall recoil. These goals are achieved within weeks after angioplasty, but with current technology stents permanently remain in the artery, with many limitations including the need for long-term antiplatelet treatment to avoid thrombosis. We report a prospective multicentre clinical trial of coronary implantations of absorbable magnesium stents. METHODS We enrolled 63 patients (44 men; mean age 61.3 [SD 9.5 years]) in eight centres with single de novo lesions in a native coronary artery in a multicentre, non-randomised prospective study. Follow-up included coronary angiography and intravascular ultrasound at 4 months and clinical assessment at 6 months and 12 months. The primary endpoint was cardiac death, non-fatal myocardial infarction, or clinically driven target lesion revascularisation at 4 months FINDINGS 71 stents, 10-15 mm in length and 3.0-3.5 mm in diameter, were successfully implanted after pre-dilatation in 63 patients. Diameter stenosis was reduced from 61.5 (SD 13.1%) to 12.6 (5.6%) with an acute gain of 1.41 mm (0.46 mm) and in-stent late loss of 1.08 mm (0.49 mm). The ischaemia-driven target lesion revascularisation rate was 23.8% after 4 months, and the overall target lesion revascularisation rate was 45% after 1 year. No myocardial infarction, subacute or late thrombosis, or death occurred. Angiography at 4 months showed an increased diameter stenosis of 48.4 (17.0%). After serial intravascular ultrasound examinations, only small remnants of the original struts were visible, well embedded into the intima. Neointimal growth and negative remodelling were the main operating mechanisms of restenosis. INTERPRETATION This study shows that biodegradable magnesium stents can achieve an immediate angiographic result similar to the result of other metal stents and can be safely degraded after 4 months. Modifications of stent characteristics with prolonged degradation and drug elution are currently in development.

Predictors of Coronary Stent Thrombosis: The Dutch Stent Thrombosis Registry

OBJECTIVES This study sought to comprehensively identify predictors of stent thrombosis (ST). BACKGROUND Given the devastating consequences of ST, efforts should be directed toward risk stratification to identify patients at highest risk for ST. METHODS Consecutive patients with angiographic ST were enrolled. Patients who did not suffer from a ST were randomly selected in a 2:1 ratio and were matched for: 1) percutaneous coronary intervention (PCI) indication; 2) same date of index PCI; and 3) same interventional center. RESULTS Of 21,009 patients treated with either a bare-metal or drug-eluting stent, 437 patients (2.1%) presented with a definite ST. A total of 140 STs were acute, 180 were subacute, 58 were late, and 59 were very late. Undersizing of the coronary stent, Thrombolysis In Myocardial Infarction flow grade <3, present malignancy, presence of intermediate coronary artery disease proximal and distal to the culprit lesion, dissection, lack of aspirin, bifurcation lesions, ejection fraction <30%, and younger age were associated with ST. The lack of clopidogrel therapy at the time of ST in the first 30 days after the index PCI (hazard ratio [HR]: 36.5, 95% confidence interval [CI]: 8.0 to 167.8), between 30 days and 6 months after the index PCI (HR: 4.6, 95% CI: 1.4 to 15.3), and beyond 6 months (HR: 5.9, 95% CI: 1.7 to 19.8) after the index PCI was strongly associated with ST. CONCLUSIONS Important correlates of ST were identified. Discontinuation of clopidogrel, undersizing of the coronary stent, present malignancy, and intermediate (>or=50% to <70% stenosis) coronary artery disease proximal to the culprit lesion were the strongest predictors of ST.

Fractional Flow Reserve to Determine the Appropriateness of Angioplasty in Moderate Coronary Stenosis

Background—PTCA of a coronary stenosis without documented ischemia at noninvasive stress testing is often performed, but its benefit is unproven. Coronary pressure–derived fractional flow reserve (FFR) is an invasive index of stenosis severity that is a reliable substitute for noninvasive stress testing. A value of 0.75 identifies stenoses with hemodynamic significance. Methods and Results—In 325 patients for whom PTCA was planned and who did not have documented ischemia, FFR of the stenosis was measured. If FFR was >0.75, patients were randomly assigned to deferral (deferral group; n=91) or performance (performance group; n=90) of PTCA. If FFR was <0.75, PTCA was performed as planned (reference group; n=144). Clinical follow-up was obtained at 1, 3, 6, 12, and 24 months. Event-free survival was similar between the deferral and performance groups (92% versus 89% at 12 months and 89% versus 83% at 24 months) but was significantly lower in the reference group (80% at 12 months and 78% at 24 months). In addi...

Evaluation of the Second Generation of a Bioresorbable Everolimus Drug-Eluting Vascular Scaffold for Treatment of De Novo Coronary Artery Stenosis Six-Month Clinical and Imaging Outcomes

OBJECTIVES The aim of this study was to demonstrate that the prevention of early scaffold area shrinkage of the ABSORB BVS (Rev.1.1, Abbott Vascular, Santa Clara, California) was sustained and not simply delayed by a few months. BACKGROUND With improved scaffold design and modified manufacturing process of its polymer, the second iteration of ABSORB (BVS 1.1) has improved performance to prevent a scaffold area reduction at 6 months. METHODS Fifty-six patients were enrolled and received 57 ABSORB scaffolds. Quantitative coronary angiography, intravascular ultrasound (IVUS), analysis of radiofrequency backscattering, echogenicity and optical coherence tomography (OCT) were performed at baseline and at 12-month follow-up. RESULTS Overall the scaffold area remained unchanged with IVUS as well as with OCT, whereas the radiofrequency backscattering and the echogenicity of the struts decreased by 16.8% (p < 0.001) and 20% (p < 0.001), respectively; more specifically, the strut core area on OCT decreased by 11.4% (p = 0.003). Despite the absence of scaffold area loss, pharmacological vasomotion was restored. On an intention-to-treat basis, the angiographic late lumen loss amounted to 0.27 ± 0.32 mm with an IVUS relative decrease in minimal lumen area of 1.94% (p = 0.12), without significant changes in mean lumen area. The OCT at follow-up showed that 96.69% of the struts were covered and that malapposition, initially observed in 18 scaffolds was only detected at follow-up in 4 scaffolds. Two patients experienced peri-procedural and iatrogenic myocardial infarction, respectively, whereas 2 underwent repeat intervention, resulting in the major adverse cardiac event rate of 7.1% (4 of 56). CONCLUSIONS The 12-month performance of the second-generation ABSORB bioresorbable everolimus-eluting scaffold justifies the conduct of a randomized trial against current best standards. (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System [BVS EECSS] in the Treatment of Patients With de Novo Native Coronary Artery Lesions; NCT00856856).

Evaluation of the Second Generation of a Bioresorbable Everolimus Drug-Eluting Vascular Scaffold for Treatment of De Novo Coronary Artery StenosisClinical Perspective

Background— The first generation of the bioresorbable everolimus drug-eluting vascular scaffold showed signs of shrinkage at 6 months, which largely contributed to late luminal loss. Nevertheless, late luminal loss was less than that observed with bare metal stents. To maintain the mechanical integrity of the device up to 6 months, the scaffold design and manufacturing process of its polymer were modified. Methods and Results— Quantitative coronary angiography, intravascular ultrasound with analysis of radiofrequency backscattering, and as an optional assessment, optical coherence tomography (OCT) were performed at baseline and at a 6-month follow-up. Forty-five patients successfully received a single bioresorbable everolimus drug-eluting vascular scaffold. One patient had postprocedural release of myocardial enzyme without Q-wave occurrence; 1 patient with OCT-diagnosed disruption of the scaffold caused by excessive postdilatation was treated 1 month later with a metallic drug-eluting stent. At follow-up, 3 patients declined recatheterization, 42 patients had quantitative coronary angiography, 37 had quantitative intravascular ultrasound, and 25 had OCT. Quantitative coronary angiography disclosed 1 edge restenosis (1 of 42; in-segment binary restenosis, 2.4%). At variance with the ultrasonic changes seen with the first generation of bioresorbable everolimus drug-eluting vascular scaffold at 6 months, the backscattering of the polymeric struts did not decrease over time, the scaffold area was reduced by only 2.0% with intravascular ultrasound, and no change was noted with OCT. On an intention-to-treat basis, the late lumen loss amounted to 0.19±0.18 mm with a limited relative decrease in minimal luminal area of 5.4% on intravascular ultrasound. OCT showed at follow-up that 96.8% of the struts were covered and that malapposition of at least 1 strut, initially observed in 12 scaffolds, was detected at follow-up in only 3 scaffolds. Mean neointimal growth measured by OCT between and on top of the polymeric struts equaled 1.25 mm2, or 16.6% of the scaffold area. Conclusion— Modified manufacturing process of the polymer and geometric changes in the polymeric platform have substantially improved the medium-term performance of this new generation of drug-eluting scaffold to become comparable to those of current drug eluting stents. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00856856.

Quantification of recruitable coronary collateral blood flow in conscious humans and its potential to predict future ischemic events

OBJECTIVES The present study was designed to evaluate the applicability of a pressure-flow equation for quantitative calculation of recruitable collateral blood flow at coronary artery occlusion in conscious patients and to investigate the value of that index to predict future ischemic events. BACKGROUND Recent experimental studies have indicated that recruitable collateral blood flow at coronary artery occlusion can be expressed as a fraction of normal maximal myocardial blood flow by simultaneous recordings of mean arterial, coronary wedge and central venous pressures, respectively. This index is called the pressure-derived fractional collateral flow and is independent of hemodynamic loading conditions. METHODS In 120 patients undergoing elective coronary angioplasty, mean arterial, coronary wedge and central venous pressures were measured at balloon inflations of 2 min. All patients had a recent exercise electrocardiogram (ECG) with positive findings showing clearly distinguishable, reversible ECG abnormalities, enabling recognition of ischemia at balloon inflation. Fractional collateral blood flow at angioplasty was calculated by coronary wedge pressure minus central venous pressure divided by mean arterial pressure minus central venous pressure and correlated to the presence or absence of ischemia at balloon inflation. Ischemic events were monitored during a follow-up period of 6 to 22 months. RESULTS In 90 of the 120 patients, ischemia was present at balloon inflation, and in 82 of these patients, fractional collateral blood flow was < or = 23%. By contrast, in 29 patients, no ischemia was present, and fractional collateral blood flow was > 24% in all 29. During the follow-up period, 16 patients had an ischemic event. Fifteen of these 16 patients were in the group with insufficient collateral flow (p < 0.05). CONCLUSIONS To our knowledge, this study presents the first method for quantitative assessment of recruitable collateral blood flow in humans in the catheterization laboratory. Sufficient and insufficient collateral circulation can be reliably distinguished by this method. Use of this method can also help to provide more insight into the extent and behavior of the collateral circulation for investigational purposes and may have potential clinical implications.

Evaluation of the Second Generation of a Bioresorbable Everolimus-Eluting Vascular Scaffold for the Treatment of De Novo Coronary Artery Stenosis

OBJECTIVES The aim of this study was to demonstrate that the prevention of early scaffold area shrinkage of the ABSORB BVS (Rev.1.1, Abbott Vascular, Santa Clara, California) was sustained and not simply delayed by a few months. BACKGROUND With improved scaffold design and modified manufacturing process of its polymer, the second iteration of ABSORB (BVS 1.1) has improved performance to prevent a scaffold area reduction at 6 months. METHODS Fifty-six patients were enrolled and received 57 ABSORB scaffolds. Quantitative coronary angiography, intravascular ultrasound (IVUS), analysis of radiofrequency backscattering, echogenicity and optical coherence tomography (OCT) were performed at baseline and at 12-month follow-up. RESULTS Overall the scaffold area remained unchanged with IVUS as well as with OCT, whereas the radiofrequency backscattering and the echogenicity of the struts decreased by 16.8% (p < 0.001) and 20% (p < 0.001), respectively; more specifically, the strut core area on OCT decreased by 11.4% (p = 0.003). Despite the absence of scaffold area loss, pharmacological vasomotion was restored. On an intention-to-treat basis, the angiographic late lumen loss amounted to 0.27 ± 0.32 mm with an IVUS relative decrease in minimal lumen area of 1.94% (p = 0.12), without significant changes in mean lumen area. The OCT at follow-up showed that 96.69% of the struts were covered and that malapposition, initially observed in 18 scaffolds was only detected at follow-up in 4 scaffolds. Two patients experienced peri-procedural and iatrogenic myocardial infarction, respectively, whereas 2 underwent repeat intervention, resulting in the major adverse cardiac event rate of 7.1% (4 of 56). CONCLUSIONS The 12-month performance of the second-generation ABSORB bioresorbable everolimus-eluting scaffold justifies the conduct of a randomized trial against current best standards. (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System [BVS EECSS] in the Treatment of Patients With de Novo Native Coronary Artery Lesions; NCT00856856).

Safety and performance of the drug-eluting absorbable metal scaffold (DREAMS) in patients with de-novo coronary lesions: 12 month results of the prospective, multicentre, first-in-man BIOSOLVE-I trial

BACKGROUND Bioabsorbable vascular scaffolds were developed to overcome limitations of permanent bare-metal or drug-eluting coronary stents—ie, stent thrombosis (despite prolonged dual antiplatelet therapy), the life-long presence of a caged vessel segment that does not allow vasomotion or remodelling, and chronic vessel wall inflammation. We assessed the safety and performance of a new magnesium-based paclitaxel-eluting absorbable metal scaffold in symptomatic patients with de-novo coronary lesions. METHODS We did a prospective, multicentre, first-in-man trial (BIOSOLVE-1) of the drug-eluting absorbable metal scaffold (DREAMS). 46 patients with 47 lesions were enrolled at five European centres. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularisation, at 6 and 12 months. Clinical follow-up was scheduled at 1, 6, 12, 24, and 36 months. Patients were consecutively assigned to angiographic and intravascular ultrasonographic follow-up at 6 months or 12 months. Optical coherence tomography was done in some patients. All patients were recommended to take dual antiplatelet therapy for at least 12 months. This trial is registered with ClinicalTrials.gov, number NCT01168830. FINDINGS Overall device and procedural success was 100%. Two of 46 (4%) patients had target lesion failure at 6 months (both clinically driven target lesion revascularisations), which rose to three of 43 (7%) at 12 months (one periprocedural target vessel myocardial infarction occurred during angiography at the 12 month follow-up visit). We noted no cardiac death or scaffold thrombosis. INTERPRETATION Our results show feasibility, a good safety profile, and promising clinical and angiographic performance results up to 12 months for DREAMS. Our promising clinical results show that absorbable metal scaffolds might be an alternative to polymeric absorbable scaffolds. FUNDING Biotronik.

Coronary pressure measurement to assess the hemodynamic significance of serial stenoses within one coronary artery: Validation in humans

BackgroundWhen several stenoses are present within 1 coronary artery, the hemodynamic significance of each stenosis is influenced by the presence of the other(s), and the calculation of coronary and fractional flow reserve (CFR and FFR) for each individual stenosis is confounded. Recently, we developed and experimentally validated a method to determine the true FFR of each stenosis as it would be after the removal of the other stenosis; the true FFR can be reliably predicted by coronary pressures measured before treatment at specific locations within the coronary artery using equations accounting for stenosis interaction. The aim of the present study was to test the validity of these equations in humans. Methods and ResultsIn this study of 32 patients with 2 serial stenoses in 1 coronary artery, relevant pressures were measured before the intervention, after the treatment of 1 stenosis, and after the treatment of both stenoses. The true FFR of each stenosis (FFRtrue) was directly measured after the elimination of the other stenosis and compared with the value predicted (FFRpred) from the initial pressure measurements before treatment. Although the hyperemic gradient across 1 stenosis increased significantly (from 10±7 to 19±11 mm Hg after treatment of the other stenosis), FFRpred was close to FFRtrue in all patients (0.78±0.12 versus 0.78±0.11 mm Hg;r =0.92; &Dgr;%=4±0%). Without accounting for stenosis interaction, the value of FFR for each stenosis would have been significantly overestimated (0.85±0.08;P <0.01). ConclusionsCoronary pressure measurements made by a pressure wire at maximum hyperemia provide a simple, practical method for assessing the individual hemodynamic significance of multiple stenoses within the same artery.