Instantaneous coronary collateral function during supine bicycle exercise

The instantaneous response of the collateral circulation to isometric physical exercise in patients with non-occlusive coronary artery disease (CAD) is not known.

Plaque characteristics of nonobstructive coronary lesions in diabetic patients: an intravascular ultrasound virtual histology analysis

Patients with diabetes mellitus are known to be at increased risk for acute cardiovascular events. We used intravascular ultrasound virtual histology (IVUS-VH) to examine whether nonobstructive coronary artery lesions of diabetic patients have distinct plaque composition and morphology compared with nondiabetic patients.

A randomised determination of the effect of fluvastatin and atorvastatin on top of dual antiplatelet treatment on platelet aggregation after implantation of coronary drug-eluting stents. The EFA-Trial

Drug-drug interaction between statins metabolised by cytochrome P450 3A4 and clopidogrel have been claimed to attenuate the inhibitory effect of clopidogrel. However, published data regarding this drug-drug interaction are controversial. We aimed to determine the effect of fluvastatin and atorvastatin on the inhibitory effect of dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel. One hundred one patients with symptomatic stable coronary artery disease undergoing percutaneous coronary intervention and drug-eluting stent implantation were enrolled in this prospective randomised study. After an interval of two weeks under dual antiplatelet therapy with ASA and clopidogrel, without any lipid-lowering drug, 87 patients were randomised to receive a treatment with either fluvastatin 80 mg daily or atorvastatin 40 mg daily in addition to the dual antiplatelet therapy for one month. Platelet aggregation was assessed using light transmission aggregometry and whole blood impedance platelet aggregometry prior to randomisation and after one month of receiving assigned statin and dual antiplatelet treatment. Platelet function assessment after one month of statin and dual antiplatelet therapy did not show a significant change in platelet aggregation from 1st to 2nd assessment for either statin group. There was also no difference between atorvastatin and fluvastatin treatment arms. In conclusion, neither atorvastatin 40 mg daily nor fluvastatin 80 mg daily administered in combination with standard dual antiplatelet therapy following coronary drug-eluting stent implantation significantly interfere with the antiaggregatory effect of ASA and clopidogrel.

Physical coronary arteriogenesis: a human "model" of collateral growth promotion

In patients with coronary artery disease, the size of myocardial infarction mainly determines the subsequent clinical outcome. Accordingly, it is the primary strategy to decrease cardiovascular mortality by minimizing infarct size. Promotion of collateral artery growth (arteriogenesis) is an appealing option of reducing infarct size. It has been demonstrated in experimental models that tangential fluid shear stress is the major trigger of arterial remodeling and, thus, of collateral growth. Lower-leg, high-pressure external counterpulsation triggered to occur during diastole induces a flow velocity signal and thus tangential endothelial shear stress in addition to the flow signal caused by cardiac stroke volume. We here present two cases of cardiac transplant recipients as human "models" of physical coronary arteriogenesis, providing an example of progressing and regressing clinical arteriogenesis, and review available evidence from clinical studies on other feasible forms of physical arteriogenesis.

The human coronary collateral circulation

Coronary collaterals are an alternative source of blood supply to myocardium jeopardized by ischaemia. Well-developed coronary collateral arteries in patients with coronary artery disease (CAD) mitigate myocardial infarcts and improve survival.

Analysis of coronary bifurcations by intravascular ultrasound and virtual histology

Background Regional differences in shear stress have been identified as reason for early plaque formation in vessel bifurcations. We aimed to investigate regional plaque morphology and composition using intravascular ultrasound (IVUS) and virtual histology (IVUS–VH) in coronary artery bifurcations. Methods We performed IVUS and IVUS–VH studies at coronary bifurcations to analyze segmental plaque burden and composition of different segments in relation to their orientation to the bifurcation. Results A total of 236 patients with a mean age of 59 ± 11 years (69% male) were analyzed. Plaque burden was higher at the contralateral vessel wall facing the bifurcation compared to the ipsilateral vessel wall and this difference was true for proximal and distal segments (proximal: 37 ± 12% and 45 ± 15% for segments at the ipsilateral and contralateral vessel wall, respectively, p < 0.001; distal: 37 ± 10% and 47 ± 15% for segments at the ipsilateral and contralateral vessel wall, respectively, p < 0.001). In addition, these segments exhibited a higher proportion of dense calcium and a lower proportion of fibrous tissue and fibro fatty tissue. Conclusions Segments on the contralateral wall of the bifurcation which have previously been identified as regions with low shear stress not only exhibited a higher plaque burden, but also a higher degree of calcification.

Value of age, creatinine, and ejection fraction (ACEF score) in assessing risk in patients undergoing percutaneous coronary interventions in the 'All-Comers' LEADERS trial

Background— The age, creatinine, and ejection fraction (ACEF) score (age/left ventricular ejection fraction+1 if creatinine >2.0 mg/dL) has been established as an effective predictor of clinical outcomes in patients undergoing elective coronary artery bypass surgery; however, its utility in “all-comer” patients undergoing percutaneous coronary intervention is yet unexplored. Methods and Results— The ACEF score was calculated for 1208 of the 1707 patients enrolled in the LEADERS trial. Post hoc analysis was performed by stratifying clinical outcomes at the 1-year follow-up according to ACEF score tertiles: ACEFlow ≤1.0225, 1.0225< ACEFmid ≤1.277, and ACEFhigh >1.277. At 1-year follow-up, there was a significantly lower number of patients with major adverse cardiac event–free survival in the highest tertile of the ACEF score (ACEFlow=92.1%, ACEFmid=89.5%, and ACEFhigh=86.1%; P=0.0218). Cardiac death was less frequent in ACEFlow than in ACEFmid and ACEFhigh (0.7% vs 2.2% vs 4.5%; hazard ratio=2.22, P=0.002) patients. Rates of myocardial infarction were significantly higher in patients with a high ACEF score (6.7% for ACEFhigh vs 5.2% for ACEFmid and 2.5% for ACEFlow; hazard ratio=1.6, P=0.006). Clinically driven target-vessel revascularization also tended to be higher in the ACEFhigh group, but the difference among the 3 groups did not reach statistical significance. The rate of composite definite, possible, and probable stent thrombosis was also higher in the ACEFhigh group (ACEFlow=1.2%, ACEFmid=3.5%, and ACEFhigh=6.2%; hazard ratio=2.04, P<0.001). Conclusions— ACEF score may be a simple way to stratify risk of events in patients treated with percutaneous coronary intervention with respect to mortality and risk of myocardial infarction.

Meta-analysis: diagnostic performance of low-radiation-dose coronary computed tomography angiography

A new radiation dose-saving technique for noninvasive coronary artery imaging with computed tomography (CT) is available.

Myocardial blood volume and coronary resistance during and after coronary angioplasty

Animal experiments have shown that the coronary circulation is pressure distensible, i.e., myocardial blood volume (MBV) increases with perfusion pressure. In humans, however, corresponding measurements are lacking so far. We sought to quantify parameters reflecting coronary distensibility such as MBV and coronary resistance (CR) during and after coronary angioplasty. Thirty patients with stable coronary artery disease underwent simultaneous coronary perfusion pressure assessment and myocardial contrast echocardiography (MCE) of 37 coronary arteries and their territories during and after angioplasty. MCE yielded MBV and myocardial blood flow (MBF; in ml · min(-1) · g(-1)). Complete data sets were obtained in 32 coronary arteries and their territories from 26 patients. During angioplasty, perfusion pressure, i.e., coronary occlusive pressure, and MBV varied between 9 and 57 mmHg (26.9 ± 11.9 mmHg) and between 1.2 and 14.5 ml/100 g (6.7 ± 3.7 ml/100 g), respectively. After successful angioplasty, perfusion pressure and MBV increased significantly (P < 0.001 for both) and varied between 64 and 118 mmHg (93.5 ± 12.8 mmHg) and between 3.7 and 17.3 ml/100 g (9.8 ± 3.4 ml/100 g), respectively. Mean MBF increased from 31 ± 20 ml · min(-1) · g(-1) during coronary occlusion, reflecting collateral flow, to 121 ± 33 ml · min(-1) · g(-1) (P < 0.01), whereas mean CR, i.e., the ratio of perfusion pressure and MBF, decreased by 20% (P < 0.001). In conclusion, the human coronary circulation is pressure distensible. MCE allows for the quantification of CR and MBV in humans.

Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease

The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone.

Determinants of prognostically relevant intracoronary electrocardiogram ST-segment shift during coronary balloon occlusion

The prognostic relevance of quantitative an intracoronary occlusive electrocardiographic (ECG) ST-segment shift and its determinants have not been investigated in humans. In 765 patients with chronic stable coronary artery disease, the following simultaneous quantitative measurements were obtained during a 1-minute coronary balloon occlusion: intracoronary ECG ST-segment shift (recorded by angioplasty guidewire), mean aortic pressure, mean distal coronary pressure, and mean central venous pressure (CVP). Collateral flow index (CFI) was calculated as follows: (mean distal coronary pressure minus CVP)/(mean aortic pressure minus CVP). During an average follow-up duration of 50 ± 34 months, the cumulative mortality rate from all causes was significantly lower in the group with an ST-segment shift <0.1 mV (n = 89) than in the group with an ST-segment shift ≥0.1 mV (n = 676, p = 0.0211). Factors independently related to intracoronary occlusive ECG ST-segment shift <0.1 mV (r(2) = 0.189, p <0.0001) were high CFI (p <0.0001), intracoronary occlusive RR interval (p = 0.0467), right coronary artery as the ischemic region (p <0.0001), and absence of arterial hypertension (p = 0.0132). "High" CFI according to receiver operating characteristics analysis was ≥0.217 (area under receiver operating characteristics curve 0.647, p <0.0001). In conclusion, absence of ECG ST-segment shift during brief coronary occlusion in patients with chronic coronary artery disease conveys a decreased mortality and is directly influenced by a well-developed collateral supply to the right versus left coronary ischemic region and by the absence of systemic hypertension in a patient's history.

Registry for the Evaluation of the Prognostik value of a novel integrated imaging approach combining Single Photon Emission Computed Tomography with coronary calcification imaging (REPROSPECT)

AIMS: Although an added diagnostic and prognostic value of the global coronary artery calcification (CAC) score as an adjunct to single-photon emission computed tomography (SPECT)-myocardial perfusion image (MPI) has been repeatedly documented, none of the previous studies took advantage of the anatomic information provided by the unenhanced cardiac CT. Therefore, no co-registration has so far been used to match a myocardial perfusion defect with calcifications in the subtending coronary artery. To evaluate the prognostic value of integrating SPECT-MPI with CAC images were obtained from non-enhanced cardiac computed tomography (CT) for attenuation correction to predict major adverse cardiac events (MACE). METHODS AND RESULTS: Follow-up was obtained in 462 patients undergoing a 1-day stress/rest (99m)Tc-teterofosmin SPECT and non-enhanced cardiac CT for attenuation correction. Survival free of MACE was determined using the Kaplan-Meier method. After integrating MPI and CT findings, patients were divided into three groups (i) MPI defect matched by calcification (CAC ≥ 1) in the subtending coronary artery (ii) unmatched MPI and CT finding (iii) normal finding by MPI and CT. At a mean follow-up of 34.5 ± 13 months, a MACE was observed in 80 patients (33 death, 6 non-fatal myocardial infarction, 9 hospitalizations due to unstable angina, and 32 revascularizations). Survival analysis revealed the most unfavourable outcome (P < 0.001 log-rank test) for patients with a matched finding. CONCLUSION: In the present study, a novel approach using a combined integration of cardiac SPECT-CAC imaging allows for refined risk stratification, as a matched defect emerged as an independent predictor of MACE.

Coronary collateral function long after drug-eluting stent implantation

OBJECTIVES: This study was designed to compare coronary collateral function in patients after bare-metal stent (BMS) or drug-eluting stent (DES) implantation. BACKGROUND: Drug-eluting stents have an inhibitory effect on the production of cytokines, chemotactic proteins, and growth factors, and may therefore negatively affect coronary collateral growth. METHODS: A total of 120 patients with long-term stable coronary artery disease (CAD) after stent implantation were included. Both the BMS group and the DES group comprised 60 patients matched for in-stent stenosis severity of the vessel undergoing collateral flow index (CFI) measurement at follow-up and for the duration of follow-up. The primary end point of the investigation was invasively determined coronary collateral function 6 months after stent implantation. Collateral function was assessed by simultaneous aortic, coronary wedge, and central venous pressure measurements (yielding CFI) and by intracoronary electrocardiogram during balloon occlusion. RESULTS: There were no differences between the groups regarding age, gender, body mass index, frequency of cardiovascular risk factors, use of cardiovascular drugs, severity of CAD, or site of coronary artery stenoses. Despite equal in-stent stenosis severity (46 +/- 34% and 45 +/- 36%) and equal follow-up duration (6.2 +/- 10 months and 6.5 +/- 5.4 months), CFI was diminished in the DES versus BMS group (0.154 +/- 0.097 vs. 0.224 +/- 0.142; p = 0.0049), and the rate of collaterals insufficient to prevent ischemia during occlusion (intracoronary electrocardiographic ST-segment elevation > or =0.1 mV) was higher with 50 of 60 patients in the DES group and 33 of 60 patients in the BMS group (p = 0.001). CONCLUSIONS: Collateral function long after coronary stenting is impaired with DES (sirolimus and paclitaxel) when compared with BMS. Considering the protective nature of collateral vessels, this could lead to more serious cardiac events in the presence of an abrupt coronary occlusion.

Sirolimus-eluting coronary stents in small vessels

BACKGROUND: This prospective multicenter study compared angiographic in-lesion late lumen loss in de novo native coronary artery lesions (vessel diameter range 2.25-2.75 mm, length range > or = 15 to < or = 30 mm) 8 months after the implantation of a sirolimus-eluting stent with that of similar vessels with the same drug-eluting stent or a bare stent of the SIRIUS study (historical controls). METHODS AND RESULTS: One hundred one patients (study group) were matched and compared with 323 patients receiving the bare stent (bare control group) and with 350 receiving the Cypher stent (Cypher control group) in the SIRIUS trial. Mean in-lesion late loss in the study group was lower than that in the bare control group (0.20 versus 0.76 mm, P < .0001) and not inferior to that in the Cypher control group (0.27 mm, P = .3). Adverse event rates (death and myocardial infarction) were similar between groups. At 8 months, target lesion revascularization rates were 0% in the study group, 13.2% in the bare control group (P < .001), and 4.6% in the Cypher control group (P = .03). CONCLUSIONS: The Cypher Bx Velocity stent was confirmed to be superior to the bare Bx Velocity stent in small coronary vessels in terms of in-lesion late loss 8 months after implantation.

Collateral-flow measurements in humans by myocardial contrast echocardiography: validation of coronary pressure-derived collateral-flow assessment

AIMS: Myocardial blood flow (MBF) is the gold standard to assess myocardial blood supply and, as recently shown, can be obtained by myocardial contrast echocardiography (MCE). The aims of this human study are (i) to test whether measurements of collateral-derived MBF by MCE are feasible during elective angioplasty and (ii) to validate the concept of pressure-derived collateral-flow assessment. METHODS AND RESULTS: Thirty patients with stable coronary artery disease underwent MCE of the collateral-receiving territory during and after angioplasty of 37 stenoses. MCE perfusion analysis was successful in 32 cases. MBF during and after angioplasty varied between 0.060-0.876 mL min(-1) g(-1) (0.304+/-0.196 mL min(-1) g(-1)) and 0.676-1.773 mL min(-1) g(-1) (1.207+/-0.327 mL min(-1) g(-1)), respectively. Collateral-perfusion index (CPI) is defined as the rate of MBF during and after angioplasty varied between 0.05 and 0.67 (0.26+/-0.15). During angioplasty, simultaneous measurements of mean aortic pressure, coronary wedge pressure, and central venous pressure determined the pressure-derived collateral-flow index (CFI(p)), which varied between 0.04 and 0.61 (0.23+/-0.14). Linear-regression analysis demonstrated an excellent agreement between CFI(p) and CPI (y=0.88 x +0.01; r(2)=0.92; P<0.0001). CONCLUSION: Collateral-derived MBF measurements by MCE during angioplasty are feasible and proved that the pressure-derived CFI exactly reflects collateral relative to normal myocardial perfusion in humans.