Mariano Pellicano

Intracoronary Adenosine: Dose-Response Relationship With Hyperemia.

OBJECTIVES The present study sought to establish the dosage of intracoronary (IC) adenosine associated with minimal side effects and above which no further increase in flow can be expected. BACKGROUND Despite the widespread adoption of IC adenosine in clinical practice, no wide-ranging, dose-response study has been conducted. A recurring debate still exists regarding its optimal dose. METHODS In 30 patients, Doppler-derived flow velocity measurements were obtained in 10 right coronary arteries (RCAs) and 20 left coronary arteries (LCAs) free of stenoses >20% in diameter. Flow velocity was measured at baseline and after 8 ml bolus administrations of arterial blood, saline, contrast medium, and 9 escalating doses of adenosine (4 to 500 μg). The hyperemic value was expressed in percent of the maximum flow velocity reached in a given artery (Q/Qmax, %). RESULTS Q/Qmax did not increase significantly beyond dosages of 60 μg for the RCA and 160 μg for LCA. Heart rate did not change, whereas mean arterial blood pressure decreased by a maximum of 7% (p < 0.05) after bolus injections of IC adenosine. The incidence of transient A-V blocks was 40% after injection of 100 μg in the RCA and was 15% after injection of 200 μg in the LCA. The duration of the plateau reached 12 ± 13 s after injection of 100 μg in the RCA and 21 ± 6 s after the injection of 200 μg in the LCA. A progressive prolongation of the time needed to return to baseline was observed. Hyperemic response after injection of 8 ml of contrast medium reached 65 ± 36% of that achieved after injection of 200 μg of adenosine. CONCLUSIONS This wide-ranging, dose-response study indicates that an IC adenosine bolus injection of 100 μg in the RCA and 200 μg in the LCA induces maximum hyperemia while being associated with minimal side effects.

Revascularization decisions in patients with stable angina and intermediate lesions: Results of the international survey on interventional strategy

Background—Fractional flow reserve (FFR) measurement of intermediate coronary stenoses is recommended by guidelines when demonstration of ischemia by noninvasive testing is unavailable. The study aims to evaluate the penetration of this recommendation into current thinking about revascularization strategies for stable coronary artery disease. Methods and Results—International Survey on Interventional Strategy was conducted via a web-based platform. First, participants’ experiences in interventional cardiology were queried. Second, 5 complete angiograms were provided, presenting only focal intermediate stenoses. FFR and quantitative coronary angiography values were known; however, remained undisclosed. Determination of stenosis significance was asked for each lesion. In cases of uncertainty, the most appropriate adjunctive invasive diagnostic method among quantitative coronary angiography, intravascular ultrasound, optical coherence tomography, or FFR needed to be selected. International Survey on Interventional Strategy was taken by 495 participants who provided 4421 lesion evaluations. In 3158 (71%) decisions, participants relied solely on angiographic appearance that was discordant in 47% with the known FFR, using 0.80 as cutoff value. The use of FFR and imaging modalities was requested in 21% and 8%, respectively. Comparing 4 groups of participants according to the experience in FFR, angiogram-based decisions were less frequent with increasing experience (77% versus 72% versus 69% versus 67%, respectively; P<0.001). As a result, requests for FFR were more frequent (14% versus 19% versus 24% versus 28%, respectively; P<0.001) and rates of discordant decisions decreased (51% versus 49% versus 47% versus 43%, respectively; P<0.022). Conclusions—The findings confirm that, even when all potential external constraints are virtually eliminated, visual estimation continues to dominate the treatment decisions for intermediate stenoses, indicative of a worrisome disconnect between recommendations and current practice.

Significance of Intermediate Values of Fractional Flow Reserve in Patients With Coronary Artery Disease.

Background— The fractional flow reserve (FFR) value of 0.75 has been validated against ischemic testing, whereas the FFR value of 0.80 has been widely accepted to guide clinical decision making. However, revascularization when FFR is 0.76 to 0.80, within the so-called gray zone, is still debatable. Methods and Results— From February 1997 to June 2013, all patients with single-segment disease and an FFR value within the gray zone or within the 2 neighboring FFR strata (0.70–0.75 and 0.81–0.85) were included. Study end points consisted of major adverse cardiovascular events (death, myocardial infarction, and any revascularization) up to 5 years. Of 17 380 FFR measurements, 1459 patients were included. Of them, 449 patients were treated with revascularization and 1010 patients were treated with medical therapy. In the gray zone, the major adverse cardiovascular events rate was similar (37 [13.9%] versus 21 [11.2%], respectively; P=0.3) between medical therapy and revascularization, whereas a strong trend toward a higher rate of death or myocardial infarction (25 [9.4] versus 9 [4.8], P=0.06) and overall death (20 [7.5] versus 6 [3.2], P=0.059) was observed in the medical therapy group. Among medical therapy patients, a significant step-up increase in major adverse cardiovascular events rate was observed across the 3 FFR strata, especially with proximal lesion location. In revascularization patients, the major adverse cardiovascular events rate was not different across the 3 FFR strata. Conclusions— FFR in and around the gray zone bears a major prognostic value, especially in proximal lesions. These data confirm that FFR⩽0.80 is valid to guide clinical decision making.

Standardization of Fractional Flow Reserve Measurements.

Pressure wire-based fractional flow reserve is considered the standard of reference for evaluation of the ischemic potential of coronary stenoses and the expected benefit from revascularization. Accordingly, its application in daily practice or for research purposes has to be as standardized as possible to avoid technical or operator-related artifacts in pressure recordings. This document proposes a standardized way of acquiring, recording, interpreting, and archiving the pressure tracings for daily practice and for the purpose of clinical research involving a core laboratory. Proposed standardized steps enhance the uniformity of clinical practices and data interpretation.

Impact of Right Atrial Pressure on Fractional Flow Reserve Measurements: Comparison of Fractional Flow Reserve and Myocardial Fractional Flow Reserve in 1,600 Coronary Stenoses

OBJECTIVES This study sought to assess the impact of a wide range of mean right atrial pressure (Pra) on fractional flow reserve (FFR) measurements. BACKGROUND FFR invasively assesses the ischemic potential of coronary stenoses. FFR is calculated as the ratio of mean distal coronary pressure (Pd) to mean aortic pressure (Pa) during maximal hyperemia. The Pra is considered to have little impact if it is within normal range, so it is neglected in the formula. METHODS In 1,676 stenoses of 1,235 patients undergoing left-right heart catheterization for ischemic (642 [52%]) or valvular heart disease (593 [48%]), the authors compared the FFR values calculated without accounting for Pra (FFR= Pd/Pa) to the corresponding myocardial fractional flow reserve (FFRmyo) values accounting for Pra (FFRmyo = Pd - Pra/Pa - Pra). RESULTS The median Pra was 7 (interquartile range [IQR]: 5 to 10) mm Hg with a maximum of 27 mm Hg. The correlation and agreement between FFR and FFRmyo was excellent (R(2) = 0.987; slope 1.096 ± 0.003). The median FFR (0.85; IQR: 0.78 to 0.91) was slightly but statistically significantly higher than the median FFRmyo (0.83; IQR: 0.76 to 0.90; p < 0.001) with a median difference of 0.01 (IQR: 0.01 to 0.02). Values of FFR above the cutoff of 0.80 provided an FFRmyo ≤0.80 in 110 (9%) stenoses. No FFR value above 0.80 provided an FFRmyo ≤0.75. CONCLUSIONS The difference between FFR and FFRmyo was minimal even in patients with markedly increased Pra. FFR values above the gray zone (i.e., >0.80) did not yield values below the gray zone (i.e., ≤0.75) in any case, which suggests that the impact of right atrial pressure on FFR measurement is indeed negligible.

Fractional Flow Reserve–Guided Revascularization in Patients With Aortic Stenosis

Fractional flow reserve (FFR) has never been investigated in patients with aortic stenosis (AS). From 2002 to 2010, we identified 106 patients with AS and coronary artery disease with at least one intermediate lesion treated according to FFR guidance. We matched 212 contemporary control patients with AS in which revascularization was decided on angiography only. More patients in the FFR-guided group underwent percutaneous coronary intervention (24% vs 13%; p = 0.019), whereas there was a trend toward less coronary artery bypass grafting (CABG) performed. After FFR, the number of diseased vessels was downgraded within the FFR-guided group (from 1.85 ± 0.97 to 1.48 ± 1; p <0.01) and compared with the angio-guided group (1.48 ± 1 vs 1.8 ± 0.97; p <0.01). Less aortic valve replacement was reported in the FFR-guided group (46% vs 57%; p = 0.056). In patients who underwent CABG, less venous conduits (0.5 ± 0.69 vs 0.73 ± 0.76; p = 0.05) and anastomoses (0.61 ± 0.85 vs 0.94 ± 1; p = 0.032) were necessary in the FFR-guided group. Up to 5 years, we found no difference in major adverse cardiac events (38% vs 39%; p = 0.98), overall death (32% vs 31%; p = 0.68), nonfatal myocardial infarction (2% vs 2%; p = 0.79), and revascularization (8% vs 7%; p = 0.76) between the 2 groups. In conclusion, FFR guidance impacts the management of selected patients with moderate or severe AS and coronary artery disease by resulting into deferral of aortic valve replacement, more patients treated with percutaneous coronary intervention, and in patients treated with CABG, into less venous grafts and anastomoses without increasing adverse event rates up to 5 years.

Fractional flow reserve to guide and to assess coronary artery bypass grafting

The aim of this review is to highlight the role of invasive functional evaluation in patients in whom coronary artery bypass graft (CABG) is indicated, and to examine the clinical evidence available in favour of fractional flow reserve (FFR) adoption in these patients, outline appropriate use, as well as point out potential pitfalls. FFR after CABG will also be reviewed, highlighting its correct interpretation and adoption when applied to both native coronary arteries and bypass grafts. Practice European guidelines support the use of FFR to complement coronary angiography with the highest degree of recommendation (Class IA) for the assessment of coronary stenosis before undertaking myocardial revascularization when previous non-invasive functional evaluation is unavailable or not conclusive. As a result, FFR has been adopted in routine clinical practice to guide clinicians decision as to whether or not perform a revascularization. Of note, due to the increasing confidence of the interventional cardiologists, FFR guidance is also being implemented to indicate or guide CABG. This is in anticipation of supportive clear-cut evidence, since recommendations for FFR adoption were based on randomized clinical trials investigating percutaneous coronary intervention (PCI) strategies in which patients with typical indications for CABG were excluded (e.g. left main disease, valvular disease, and coronary anatomy unsuitable for PCI). Based on the critical appraisal of the literature, FFR can play an important role in risk stratification and determining management strategy of patients either before or after CABG.

Single String Technique for Coronary Bifurcation Stenting: Detailed Technical Evaluation and Feasibility Analysis

OBJECTIVES The study aimed to evaluate the adequacy and feasibility of the single string bifurcation stenting technique. BACKGROUND Double-stent techniques may be required for complex bifurcations. Currently applied methods all have their morphological or structural limitations with respect to wall coverage, multiple strut layers, and apposition rate. METHODS Single string is a novel method in which, first, the side branch (SB) stent is deployed with a single stent cell protruding into the main branch (MB). Second, the MB stent is deployed across this protruding stent cell. The procedure is completed by final kissing balloon dilation. The single string technique was first tested in vitro (n = 20) and next applied in patients (n = 11) with complex bifurcation stenoses. RESULTS All procedures were performed successfully, crossing a single stent cell in 100%. Procedure duration was 23.0 ± 7.9 min, and the fluoroscopy time was 9.4 ± 3.5 min. The results were evaluated by optical coherence tomography, showing fully apposed struts in 83.0 ± 9.2% in the bifurcation area. Residual area obstruction in the MB was 6.4 ± 5.6% and 25.0 ± 16.9% in the SB, as evaluated by micro computed tomography. All the human cases were performed successfully with excellent angiographic results: the residual area stenosis was 27 ± 8% and 29 ± 10% in the MB and in the SB, respectively, by 3-dimensional quantitative coronary angiography. No relevant periprocedural enzyme increase was observed. During follow-up (6 ± 4 months), no adverse clinical events (death, myocardial infarction, target vessel revascularization) were noted. CONCLUSIONS The single string technique for complex bifurcation dilation was shown to be adequate in vitro and feasible in humans, with favorable results in terms of stent overlap, malapposition rate, and low residual obstruction in both the MB and SB.

Effects of Prasugrel Versus Clopidogrel on Coronary Microvascular Function in Patients Undergoing Elective PCI.

Microvascular impairment has been reported in patients on clopidogrel undergoing elective percutaneous coronary intervention (PCI) [(1)][1]. The related potential mechanisms might include the high residual platelet reactivity observed in a substantial proportion of these patients pretreated with

Catheter-based measurements of absolute coronary blood flow and microvascular resistance feasibility, safety, and reproducibility in humans

Background— The principle of continuous thermodilution can be used to calculate absolute coronary blood flow and microvascular resistance (R). The aim of the study is to explore the safety, feasibility, and reproducibility of coronary blood flow and R measurements as measured by continuous thermodilution in humans. Methods and Results— Absolute coronary flow and R can be calculated by thermodilution by infusing saline at room temperature through a dedicated monorail catheter. The temperature of saline as it enters the vessel, the temperature of blood and saline mixed in the distal part of the vessel, and the distal coronary pressure were measured by a pressure/temperature sensor-tipped guidewire. The feasibility and safety of the method were tested in 135 patients who were referred for coronary angiography. No significant adverse events were observed; in 11 (8.1%) patients, bradycardia and concomitant atrioventricular block appeared transiently and were reversed immediately on interruption of the infusion. The reproducibility of measurements was tested in a subgroup of 80 patients (129 arteries). Duplicate measurements had a strong correlation both for coronary blood flow (&rgr;=0.841, P<0.001; intraclass correlation coefficient=0.89, P<0.001) and R (&rgr;=0.780, P<0.001; intraclass correlation coefficient=0.89, P<0.001). In Bland–Altman plots, there was no significant bias or asymmetry. Conclusions— Absolute coronary blood flow (in L/min) and R (in mm Hg/L/min or Wood units) can be safely and reproducibly measured with continuous thermodilution. This approach constitutes a new opportunity for the study of the coronary microcirculation.