Fernando Alfonso

Expert review document part 2: methodology, terminology and clinical applications of optical coherence tomography for the assessment of interventional procedures.

This document is complementary to an Expert Review Document on Optical Coherence Tomography (OCT) for the study of coronary arteries and atherosclerosis.1 The goal of this companion manuscript is to provide a practical guide framework for the appropriate use and reporting of the novel frequency domain (FD) OCT imaging to guide interventional procedures, with a particular interest on the comparison with intravascular ultrasound (IVUS).1–4 In the OCT Expert Review Document on Atherosclerosis, a comprehensive description of the physical principles for OCT imaging and time domain (TD) catheters (St Jude Medical, Westford, MA, USA) was provided.1 The main advantage of FD-OCT is that the technology enables rapid imaging of the coronary artery, using a non-occlusive acquisition modality. The FD-OCT catheter (DragonflyTM; St Jude Medical) employs a single-mode optical fibre, enclosed in a hollow metal torque wire that rotates at a speed of 100 r.p.s. It is compatible with a conventional 0.014″ angioplasty guide wire, inserted into a short monorail lumen at the tip. The frequency domain optical coherence tomography lateral resolution is improved in comparison with TD-OCT, while the axial resolution did not change. These features, together with reduced motion artefacts and an increased maximum field of view up to 11 mm, have significantly improved both the quality and ease of use of OCT in the catheterization laboratory.3,4 However, the imaging depth of the FD-OCT is still limited to 0.5–2.0 mm.5 The main obstacle to the adoption of TD-OCT imaging in clinical practice is that OCT cannot image through a blood field, and therefore requires clearing or flushing of blood from the lumen.1 The 6 Fr compatible DragonflyTM FD-OCT catheter is so far the only one in the market, as two other systems from Volcano and Terumo, which …

Impact of Chronic Kidney Disease on Platelet Function Profiles in Diabetes Mellitus Patients With Coronary Artery Disease Taking Dual Antiplatelet Therapy

OBJECTIVES We sought to assess the impact of renal function on platelet reactivity in patients with diabetes mellitus (DM) and coronary artery disease on aspirin and clopidogrel therapy. BACKGROUND Diabetes mellitus is a key risk factor for chronic kidney disease (CKD). In aspirin-treated DM patients the presence of moderate/severe CKD is associated with reduced clinical efficacy of adjunctive clopidogrel therapy. Whether these findings may be attributed to differences in clopidogrel-induced effects is unknown. METHODS This was a cross-sectional observational study in which DM patients taking maintenance aspirin and clopidogrel therapy were studied. Patients were categorized into 2 groups according to the presence or absence of moderate/severe CKD. Platelet aggregation after adenosine diphosphate (ADP) and collagen stimuli were assessed with light transmittance aggregometry and defined patients with high post-treatment platelet reactivity (HPPR). Markers of platelet activation, including glycoprotein IIb/IIIa activation and P-selectin expression, were also determined using flow cytometry. RESULTS A total of 306 DM patients were analyzed. Patients with moderate/severe CKD (n = 84) had significantly higher ADP-induced (60 +/- 13% vs. 52 +/- 15%, p = 0.001) and collagen-induced (49 +/- 20% vs. 41 +/- 20%, p = 0.004) platelet aggregation compared with those without (n = 222). After adjustment for potential confounders, patients with moderate/severe CKD were more likely to have HPPR after ADP (adjusted odds ratio: 3.8, 95% confidence interval: 1.7 to 8.5, p = 0.001) and collagen (adjusted odds ratio: 2.4; 95% confidence interval: 1.1 to 5.4; p = 0.029) stimuli. Markers of platelet activation were significantly increased in patients with HPPR. CONCLUSIONS In DM patients with coronary artery disease taking maintenance aspirin and clopidogrel therapy, impaired renal function is associated with reduced clopidogrel-induced antiplatelet effects and a greater prevalence of HPPR.

Coronary aneurysms after drug-eluting stent implantation: clinical, angiographic, and intravascular ultrasound findings.

OBJECTIVES This study sought to assess clinical, angiographic, and intravascular ultrasound (IVUS) findings in patients developing coronary aneurysms (CANs) after drug-eluting stent (DES) implantation. BACKGROUND The long-term safety of DES remains unsettled. METHODS This study analyzed 1,197 consecutive patients with late angiographic evaluation after DES implantation. In 15 patients (1.25%, 95% confidence interval: 0.58 to 1.93), CANs developed at follow-up. Analyses included quantitative angiography and volumetric IVUS. RESULTS DES developing CANs were more frequently implanted during acute myocardial infarction and were longer than those without this outcome. The elapsed time from DES implantation to CAN diagnosis was 313 +/- 194 days. Angiographically, maximal CAN diameter measured 5.1 +/- 1.2 mm. On IVUS, CAN external elastic lamina area was 32 +/- 13.1 mm(2) and incomplete apposition area was 12.1 +/- 8.6 mm(2). Two patients presented with acute myocardial infarction secondary to DES thrombosis. Four additional patients presented with unstable angina and underwent CAN aggressive dilation (3 were also treated for concomitant in-stent restenosis). Dual antiplatelet therapy was recommended in the remaining 9 patients who were asymptomatic at CAN diagnosis, but 1 of them eventually died of cardiogenic shock after a CAN-related myocardial infarction. After a mean follow-up of 399 +/- 347 days, the 1-year event-free survival was 49 +/- 14% and was related to CAN size on IVUS. In 2 patients, CANs disappeared at repeated late angiography and IVUS showed abluminal CAN thrombosis. CONCLUSIONS After DES implantation, CANs are rare and may be detected in asymptomatic patients. However, CANs are frequently associated with adverse clinical events as a result of DES restenosis and DES thrombosis. Further studies are required to determine the implications of this distinct new entity.

Morphometric Assessment of Coronary Stenosis Relevance With Optical Coherence Tomography : A Comparison With Fractional Flow Reserve and Intravascular Ultrasound

OBJECTIVES The study sought to assess the diagnostic efficiency of optical coherence tomography (OCT) in identifying hemodynamically severe coronary stenoses as determined by fractional flow reserve (FFR). Concomitant OCT and intravascular ultrasound (IVUS) area measurements were performed in a subgroup of patients to compare the diagnostic efficiency of both techniques. BACKGROUND The value of OCT to determine stenosis severity remains unsettled. METHODS Sixty-one stenoses with intermediate angiographic severity were studied in 56 patients. Stenoses were labeled as severe if FFR ≤0.80. OCT interrogation was performed in all cases, with concomitant IVUS imaging in 47 cases. RESULTS Angiographic stenosis severity was 50.9 ± 8% diameter stenosis with 1.28 ± 0.3 mm minimal lumen diameter. FFR was ≤0.80 in 28 (45.9%) stenoses. An overall moderate diagnostic efficiency of OCT was found (area under the curve [AUC]: 0.74; 95% confidence interval [CI]: 0.61 to 0.84), with sensitivity/specificity of 82%/63% associated with an optimal cutoff value of 1.95 mm(2). Comparison of the results in patients with simultaneous IVUS and OCT imaging revealed no significant differences in the diagnostic efficiency of OCT (AUC: 0.70; 95% CI: 0.55 to 0.83) and IVUS (AUC. 0.63; 95% CI: 0.47 to 0.77; p = 0.19). Sensitivity/specificity for IVUS was 67%/65% for an optimal cutoff value of 2.36 mm(2). In the subgroup of small vessels (reference diameter <3 mm) OCT showed a significantly better diagnostic efficiency (AUC: 0.77; 95% CI: 0.60 to 0.89) than IVUS (AUC: 0.63; 95% CI: 0.46 to 0.78) to identify functionally significant stenoses (p = 0.04). CONCLUSIONS OCT has a moderate diagnostic efficiency in identifying hemodynamically severe coronary stenoses. Although OCT seems slightly superior to IVUS for this purpose (particularly in vessels <3 mm), its low specificity precludes its use as a substitute of FFR for functional stenosis assessment.

Efficacy and Safety of Drug-Eluting Stents in Chronic Total Coronary Occlusion Recanalization: A Systematic Review and Meta-Analysis

OBJECTIVES The aim of this study was to compare the efficacy and safety of drug-eluting stent (DES) and bare-metal stent (BMS) use in chronic total occlusion (CTO) recanalization. BACKGROUND The long-term effectiveness and safety of DES use in CTO recanalization are unclear, and performance of randomized clinical trials in the field is complex. METHODS Major electronic information sources were explored for articles comparing outcomes with DES and BMS use among patients with CTO. Assessed clinical outcomes were death, myocardial infarction, target vessel revascularization, major adverse cardiac events, and stent thrombosis; angiographic outcomes were stent restenosis and stent reocclusion. RESULTS Fourteen comparative studies were identified (a total of 4,394 patients). When compared with BMS, DES significantly reduced risk of major adverse cardiac events (relative risk [RR]: 0.45, 95% confidence interval [CI]: 0.34 to 0.60, p < 0.001) and TVR (RR: 0.40, 95% CI: 0.28 to 0.58, p < 0.001) without increasing death (RR: 0.87, 95% CI: 0.66 to 1.16, p = 0.88) or myocardial infarction (RR: 0.89, 95% CI: 0.54 to 1.46, p = 0.80). This benefit was sustained at >/=3 years of follow-up. Lower RRs for restenosis (RR: 0.25, 95% CI: 0.16 to 0.41, p < 0.001) and stent reocclusion (RR: 0.30, 95% CI: 0.18 to 0.49, p < 0.001) were also observed in the DES group. A strong trend toward a higher rate of stent thrombosis was documented in DES-treated patients (RR: 2.79, 95% CI: 0.98 to 7.97, p = 0.06). CONCLUSIONS DES use in CTO recanalization is associated with significantly fewer major adverse cardiac events and fewer occurrences of target vessel revascularization, restenosis, and stent reocclusion than with BMS. Although a statistical trend toward a higher risk of stent thrombosis was observed, the use of DES in this context seems to be safe, with an overall benefit sustained in the long term.

Importance of Diastolic Fractional Flow Reserve and Dobutamine Challenge in Physiologic Assessment of Myocardial Bridging

OBJECTIVES This study reports a comparative assessment of the hemodynamic relevance of myocardial bridges (MB) using two modalities of fractional flow reserve (FFR), with and without concomitant inotropic challenge. BACKGROUND Extravascular coronary compression by means of MB is modulated by myocardial inotropism and causes intracoronary systolic pressure overshooting and negative systolic gradients across the MB. The former characteristic suggests that adequate hemodynamic assessment of MB should include inotropic stimulation. The latter characteristic might interfere with FFR by decreasing the mean pressure gradient. METHODS We compared the hemodynamic relevance of 12 lone MB in symptomatic patients using conventional (mean) and diastolic FFR. Diastolic FFR was obtained from post-processed, digitally acquired electrocardiogram and pressure signals. Previously validated cut off values of 0.75 (mean FFR) and 0.76 (diastolic FFR) for hemodynamic relevance were used. Measurements were performed at baseline and after incremental intravenous dobutamine doses. RESULTS Fractional flow reserve decreased during dobutamine challenge: mean FFR was 0.90 +/- 0.04 at baseline and 0.84 +/- 0.06 after dobutamine (p = 0.0008); similarly, diastolic FFR was 0.88 +/- 0.05 and 0.77 +/- 0.10 before and after dobutamine, respectively (p = 0.0006). Diastolic FFR identified hemodynamic relevance in five patients, whereas mean FFR did so in only one patient. The discrepancy between mean FFR and diastolic FFR increased with dobutamine challenge: the ratio of mean FFR/diastolic FFR was 1.03 at baseline and 1.09 after dobutamine (p = 0.02). During the administration of dobutamine, the discrepancy was inversely related to the systolic pressure gradient (r = 0.58, P = 0.04). CONCLUSIONS Physiologic assessment of MB should include dobutamine challenge. Because the overshooting of systolic pressure interferes with and is a cause of error in FFR measurements based on mean pressures, diastolic FFR appears to be the technique of choice for MB assessment, whereas mean FFR should be used with caution.

Assessment of Microcirculatory Remodeling With Intracoronary Flow Velocity and Pressure Measurements Validation With Endomyocardial Sampling in Cardiac Allografts

Background— Intracoronary physiology techniques have been validated extensively for the assessment of epicardial stenoses but not for the lone study of coronary microcirculation. We performed a comparison between 4 intracoronary physiological indices with the actual structural microcirculatory changes documented in transplanted hearts. Methods and Results— In 17 cardiac allograft patients without coronary stenoses, ECG, intracoronary Doppler flow velocity, and aortic pressure were digitally recorded before and during maximal hyperemia with a dedicated system. Postprocessing of data yielded 4 indices of microcirculatory status: coronary flow velocity reserve (2.13±0.59), instantaneous hyperemic diastolic velocity pressure slope (2.33±1.25 cm · s · −1mm Hg−1), coronary resistance index (1.65±0.88 mm Hg · cm−1 · s−1), and coronary resistance reserve (2.36±0.65). Quantitative morphometry was performed in endomyocardial biopsies during the same hospital intake; arteriolar obliteration (76.57±6.95%) and density (2.00±1.22 arterioles per 1 mm2) and capillary density (645±179 capillaries per 1 mm2) were measured. Univariate regression analysis between intracoronary measurements and histological findings revealed that instantaneous hyperemic diastolic velocity-pressure slope correlated with arteriolar obliteration (r=0.58, P=0.014) and capillary density (r=0.60, P=0.012). Statistical adjustment revealed an independent contribution of arteriolar obliteration (&bgr;=0.61, P=0.0009) and capillary density (&bgr;=−0.60, P=0.0008) to instantaneous hyperemic diastolic velocity-pressure slope values, resulting in an excellent predictive model (r=0.84, P=0.0002). Coronary resistance index correlated only with capillary density (r=0.70, P=0.019). Relative indices (coronary flow velocity reserve and coronary resistance reserve) did not correlate significantly with arteriolar obliteration, capillary density, or arteriolar density. Conclusions— Intracoronary indices derived from pressure and flow, particularly instantaneous hyperemic diastolic velocity-pressure slope, appear to be superior to coronary flow velocity reserve in detecting structural microcirculatory changes. Both arteriolar obliteration and capillary rarefaction seem to influence microcirculatory hemodynamics independently.

Fate of stent-related side branches after coronary intervention in patients with in-stent restenosis

OBJECTIVES We sought to assess the fate of stent (ST)-related side branches (SB) after coronary intervention in patients with in-ST restenosis. BACKGROUND In-ST restenosis constitutes a therapeutic challenge. Although the fate of lesion-related SB after conventional angioplasty or initial coronary stenting is well established, the outcome of ST-related SB in patients with in-ST restenosis undergoing repeat intervention is unknown. METHODS One hundred consecutive patients (age 61 +/- 11 years, 22 women) undergoing repeat intervention for in-ST restenosis (101 ST) were prospectively studied. Two hundred and twenty-six SB spanned by the ST were identified. The SB size, type, ostium involvement, location within the ST and take-off angle were evaluated. The SB TIMI (Thrombolysis in Myocardial Infarction trial) flow grade was studied in detail before, during, immediately after the procedure, and at late angiography. RESULTS Occlusion (TIMI flow grade = 0) was produced in 24 (10%) SB, whereas some degree of flow deterioration (> or = 1 TIMI flow grade) was observed in 57 SB (25%). The SB occlusion was associated with non-Q wave myocardial infarction in two patients (both had large and diseased SB). Side-branch occlusion at the time of initial stenting (RR [relative risk] 11.1, 95% CI [confidence interval] 3.5-35.5, p < 0.001), diabetes (RR 3.5, 95% CI 1.1-10.5, p = 0.02), SB ostium involvement (RR 5.0, 95% CI 1.4-17.2, p = 0.004), baseline SB TIMI flow grade <3 (RR 5.5, 95% CI 1.7-18.1, p = 0.005), and restenosis length (RR 1.05 95% CI 1.01-1.11, p = 0.03) were identified as independent predictors of SB occlusion. Late angiography in 19 initially occluded SB revealed that 17 (89%) were patent again. The long-term clinical event-free survival (81% vs. 82% at two years) in patients with and without initial SB occlusion was similar. CONCLUSIONS Occlusion or flow deterioration of SB spanned by the ST is relatively common during repeat intervention for in-ST restenosis. Several factors (mainly anatomic features) are useful predictors of this event. However, most SB occlusions are clinically silent and frequently reappear at follow-up.

Combined use of OCT and IVUS in spontaneous coronary artery dissection.

SPONTANEOUS CORONARY ARTERY DISSECTION (SCAD) REPRESENTS A DIAGNOSTIC CHALLENGE [(1,2)][1]. In this study, we used a combined imaging strategy, intravascular ultrasound (IVUS) and optical coherence tomography (OCT), in 8 patients with SCAD. The diagnosis of SCAD required the visualization of an

Initial Results and Long-Term Clinical and Angiographic Outcome of Coronary Stenting in Women

To assess whether gender influences the results of coronary stenting, 158 consecutive women undergoing coronary stenting were compared with 823 consecutive men. Women had more adverse baseline characteristics, a higher hospital mortality, and were independently associated with procedural failure/complications (relative risk 2.4, 95% confidence interval 1.2 to 4.8); however, the long-term event-free survival and the restenosis rate were not influenced by gender.