Silvio Fedele

Paradoxical Increase in Microvascular Resistance During Tachycardia Downstream From a Severe Stenosis in Patients With Coronary Artery Disease Reversal by Angioplasty

Background—The pathophysiology of microvascular response to a severe coronary stenosis has not been conclusively identified. The aim of this study was to characterize the human vasomotor response to pacing-induced ischemia of both the stenotic arterial segment and the distal microcirculation. Methods and Results—Sixteen patients with stable angina and single-vessel disease were studied. Blood flow velocity and transstenotic pressure gradient were monitored at baseline, after intracoronary adenosine (2 mg), and during ischemia induced by atrial pacing with and without adenosine. At the end of this protocol, the study was repeated after intracoronary phentolamine in 7 patients and after angioplasty in 9. Stenosis resistance was calculated as the ratio between mean pressure gradient and mean flow, and microvascular resistance as the ratio between mean distal pressure and mean flow; values were expressed as percent of baseline. Adenosine decreased (P <0.05) baseline microvascular resistance to 52±17%, but not stenosis resistance. Pacing increased both stenosis and microvascular resistances (244±96% and 164±60% of baseline, respectively, P <0.05). Addition of adenosine to pacing decreased both stenosis (143±96% of baseline, P <0.05 versus ischemia) and microvascular (51±17% of baseline, P <0.05 versus baseline and ischemia) resistances. Phentolamine did not affect coronary resistance at any step of the protocol. Angioplasty and stenting restored a progressive decline in microvascular resistance during pacing (51±19% of baseline, P <0.05 versus baseline). Conclusions—In patients with coronary artery disease, tachycardia-induced ischemia was associated with elevated resistance of both the stenotic segment and the microvasculature. Revascularization prevents this paradoxical behavior.

Adenosine-induced renal vasoconstriction in man

OBJECTIVE The aim of the study was to evaluate the effects of adenosine on renal blood flow in humans. METHODS Eleven normotensive patients (mean age 53 +/- 11 years) with normal renal angiograms were enrolled in the study. Arterial blood pressure, one ECG lead and arterial renal blood flow velocity, by intravascular Doppler catheter, were monitored throughout the procedure. Incremental doses (10(-5), 10(-4), 10(-3), 2 x 10(-3), 5 x 10(-3), 10(-2), 10(-1), 1 mg) were selectively injected, at 5-min intervals, in a renal artery. RESULTS Adenosine administration had no significant effects on blood pressure, heart rate and atrio-ventricular conduction. A progressive reduction in renal blood flow velocity (from 16.36 +/- 1.9 to 3.9 +/- 0.8 cm/s, P < 0.0001) was observed. Following adenosine the decrease of flow velocity was immediate and its duration was proportional to dosage (from 0.5 +/- 0.4 s at 10(-5) mg to 31 +/- 6.5 s at 1 mg). Renal angiography, repeated in four patients during flow velocity decrement, showed no changes in vessel diameter. CONCLUSIONS Exogenous adenosine-induced a marked and transient reduction in renal blood flow in man. This effect suggests that adenosine or its metabolites may be directly implicated in rapid and powerful mechanisms of cardiac output redistribution. Thus endogenous adenosine could have a role in regulating renal blood flow in physiological and pathological situations like strenuous exercise, hemorrhage shock and cardiac failure.

Platelet glycoprotein IIb/IIIa receptor blockade and coronary resistance in unstable angina

OBJECTIVES We designed a study to explore the effect of glycoprotein (GP) IIb/IIIa blockade on the atherosclerotic plaque and distal coronary vasculature. BACKGROUND Platelet GP IIb/IIIa blockers have been proven to be beneficial in acute ischemic syndromes. This effect has also been attributed to the prevention of microvascular obstruction, although the underlying mechanisms have not been fully defined. METHODS Eighteen patients with unstable refractory angina pectoris underwent cardiac catheterization and angioplasty. Trans-stenotic and microvascular resistances to flow were measured at baseline, during hyperventilation, and after intracoronary adenosine. Measurements were repeated early after abciximab administration and after successful percutaneous transluminal coronary angioplasty. RESULTS Hyperventilation induced an ischemic attack in 12 of 18 patients and increased epicardial (12.8 +/- 16.9 vs. 6.1 +/- 6.1 mm Hg/ml per min, p < 0.05) and microvascular (9.9 +/- 7.5 vs. 6.8 +/- 5.8 mm Hg/ml per min, p < 0.05) coronary resistance. Abciximab had no significant effect on epicardial resistance, although it significantly reduced distal coronary resistance under all study conditions, including baseline (4.8 +/- 4.8 mm Hg/ml per min, p < 0.01), hyperventilation (5.1 +/- 5.4 mm Hg/ml per min, p < 0.01), and intracoronary adenosine (2.7 +/- 3.0 vs. 4.3 +/- 4.3 mm Hg/ml per min, p < 0.05). The hyperventilation test became negative in all patients after abciximab administration. CONCLUSIONS These observations confirm the immediate beneficial effects of platelet GP IIb/IIIa blockade with abciximab in acute ischemic syndromes and suggest that improvement of microvascular function may play a central role in the mechanism of action of this drug.

Randomized evaluation of intralesion versus intracoronary abciximab and aspiration thrombectomy in patients with ST-elevation myocardial infarction: The COCTAIL II trial

BACKGROUND Thrombus burden and distal embolization are predictive of no-reflow during primary percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction (STEMI). We sought to compare the efficacy of pharmacological and catheter-based strategies for thrombus in patients with STEMI and high atherothrombotic burden. METHODS Between January 2012 and December 2013, 128 STEMI patients undergoing primary PCI at 5 centers were randomly assigned in a 2 × 2 factorial design to intracoronary (IC) abciximab bolus (via the guide catheter) versus intralesion (IL) abciximab bolus, each with versus without aspiration thrombectomy (AT). Study end points were residual intrastent atherothrombotic burden, defined as the number of cross-sections with residual tissue area >10% as assessed by optical coherence tomography, and indices of angiographic and myocardial reperfusion. RESULTS Residual intrastent atherothrombotic burden did not significantly differ with IL versus IC abciximab (median [interquartile range] 6.0 [1-15] vs 6.0 [2-11], P = .806) and with AT versus no aspiration (6.0 [1-13] vs 6.0 [2-12], P = .775). Intralesion abciximab administration was associated with improved angiographic myocardial reperfusion in terms of thrombolysis in myocardial infarction (TIMI) flow (3 [3-3] vs 3 [2-3], P = .040), corrected TIMI frame count (12 ± 5 vs 17 ± 16, P = .021), and myocardial blush grade (3 [2-3] vs 3 [2-3], P = .035). In particular, IL abciximab was associated with higher occurrence of final TIMI 3 flow (90% vs 73.8%, P = .032) and myocardial blush grade 3 (71.6% vs 52.4%, P = .039). Conversely, AT had no significant effect on indices of angiographic or myocardial reperfusion. CONCLUSIONS In patients with STEMI and high thrombotic burden, neither IL versus IC abciximab nor AT versus no aspiration reduced postprocedure intrastent atherothrombotic burden in patients with STEMI undergoing primary PCI. However, IL abciximab improved indices of angiographic and myocardial reperfusion compared to IC abciximab, benefits not apparent with AT.

Radial artery occlusion and hand strength after percutaneous coronary procedures: Results of the HANGAR study

Objectives: The aim of this prospective study was to evaluate muscle force of the hand, thumb, and forefinger in patients with prolonged radial occlusion after transradial percutaneous coronary procedures. Background: There are no data on hand strength and function in patients with prolonged radial occlusion after percutaneous coronary procedures. Methods: Elective patients with chronic stable angina undergoing percutaneous coronary procedures were evaluated the day before the procedure for radial artery patency, Allen test, hand grip, and thumb and forefinger pinch tests. The same measures were performed the day after the procedure and at follow‐up. At follow‐up, patients were divided in two groups according to the radial patency (group 1) or occlusion (group 2). Results: Of the 99 patients included in the study, 90 patients had a patent radial artery (group 1), and nine (9.1%) patients had an occluded artery (group 2). At baseline, there were no significant differences in hand grip test between the two groups (42 ± 11 kg in group 1 and 41 ± 17 kg in group 2, P = 0.74). In both groups, after the procedure, the hand grip test values was significantly reduced compared with baseline values (40 ± 11 kg in group 1, P < 0.0001 and 37 ± 17 kg in group 2, P = 0.007). Finally, at follow‐up, in both groups, the hand grip test values returned to baseline values. Thumb and forefinger pinch tests did not show significant differences after the procedure and at follow‐up, compared with baseline. Conclusions: Radial artery occlusion after percutaneous coronary procedures was not associated with a reduction in hand and finger strength.

Operator radiation exposure during right or left transradial coronary angiography: A phantom study

BACKGROUND Previous studies showed a possible lower radiation dose absorbed by operators comparing LRA and RRA for percutaneous coronary procedures. The reasons of this lower radiation dose are not well known. The aim of this study was to evaluate the radiation dose absorbed by operators comparing left with right radial access (LRA and RRA respectively) during a simulated diagnostic coronary angiography using a phantom. METHODS A coronary angiography examination was simulated on a phantom by 5 operators using eight projections with 5 seconds fluoroscopy each. Each operator was equipped with 4 electronic dosimeters placed at thorax, at left wrist, at left head and at hip level. Radiation doses were expressed in picosievert and normalized by dose area product. RESULTS LRA compared to RRA was associated with a significant lower operator dose at wrist (36pSv/cGYcm(2) [IQR 18-59pSv/cGYcm(2)] and 48pSv/cGYcm(2) [IQR 22-148pSv/cGYcm(2)] respectively, p=0.01) and thorax (3pSv/cGYcm(2) [IQR 2-5pSv/cGYcm(2)] and 10pSv/cGYcm(2) [6-23pSv/cGYcm(2)] respectively, p<0.001) but with a significant higher radiation dose at hip level (102pSv/cGYcm(2) [IQR 44-199pSv/cGYcm(2)] and 67pSv/cGYcm(2) [IQR 39-132pSv/cGYcm(2)] respectively, p=0.02). Conversely the radiation dose at left side of the head did not show significant differences between the two approaches. CONCLUSIONS In this phantom study simulating a diagnostic coronarography the use of LRA compared to RRA was associated with a significant lower radiation dose at wrist and thorax but with an increased dose at hip level. SUMMARY To evaluate the radiation dose absorbed by operators comparing left with right radial access (LRA and RRA respectively) we simulated a diagnostic coronary angiography using a dedicated phantom. Operators were equipped with dedicated electronic dosimeters at wrist, hip, head and thorax level. LRA compared to RRA was associated with a significant lower operator dose at wrist and thorax but with a significant higher radiation dose at hip level whereas the radiation dose at left side of the head did not show significant differences between the two approaches.

Determinants of operator radiation exposure during percutaneous coronary procedures

Background Radiation exposure is an important issue for interventional cardiologists that is often underevaluated. Our aim was to evaluate determinants of operator radiation exposure during percutaneous coronary procedures. Methods The RADIANT (NCT01974453) is a prospective, single‐center observational study involving 4 expert operators and 2 fellows performing percutaneous coronary procedures. The operator radiation dose was evaluated using dedicated electronic dosimeters in 2,028 procedures: 1,897 transradial access (TRA; 1,120 right and 777 left TRA) and 131 transfemoral access (TFA). Results In the whole population, operator radiation dose at the thorax did not differ between TFA (9 &mgr;Sv [interquartile range 5‐18 &mgr;Sv]) and TRA (9 &mgr;Sv [4‐21 &mgr;Sv]), but after propensity score matching analysis, TFA showed lower dose (9 &mgr;Sv [5‐18 &mgr;Sv]) compared with TRA (17 &mgr;Sv [9‐28 &mgr;Sv], P < .001). In the whole transradial group, left TRA (5 &mgr;Sv [2‐12 &mgr;Sv]) was associated with significant lower operator dose compared with right TRA (13 &mgr;Sv [6‐26 &mgr;Sv], P < .001).The use of adjunctive protective pelvic drapes was significantly associated with lower radiation doses compared with procedures performed without drapes (P < .001). Among the operators, an inverse relation between height and dose was observed. Finally, left projections and the use of angiographic systems not dedicated for coronary and high frame rates were all associated with a significant higher operator radiation exposure. Conclusions In a high‐volume center for transradial procedures, TFA is associated with lower operator radiation dose compared with TRA. The use of adjunctive anti‐rx drapes seems a valuable tool to reduce the higher operator radiation exposure associated with TRA. Graphical Abstract Figure. No caption available.

Radiation dose absorbed by operators during transradial percutaneous coronary procedures comparing different protective drapes: the RADIATION study

AIMS The aim of this study was to compare different radiation protection drapes in terms of radiation dose absorbed by operators during right or left transradial procedures. METHODS AND RESULTS Patients who underwent transradial coronary procedures were randomised initially into four groups: Group 1 (no drapes), Group 2 (drape on patients arm), Group 3 (pelvic drape), Group 4 (combined arm and pelvic drapes). Subsequently, each group was further randomised to right or left radial access. The primary endpoint was the operator radiation dose at the thorax. A total of 452 procedures were included. The use of drapes was associated with a lower radiation dose compared to no drapes (8.6 µSv [4.1-17.9] Group 1, 5.8 µSv [3.4-13] Group 2, 3.6 µSv [2.1-6.9] Group 3, 3.7 µSv [1.9-10.3] Group 4, p<0.001). Among radiation protection drapes groups the radiation dose was significantly lower in Groups 3 and 4 compared to Group 2 (p<0.008). Compared to Group 1, the dose in Group 2 was significantly lower only in right radial procedures (p<0.008) whereas in Groups 3 and 4 the dose was significantly lower in both radial accesses (p<0.008). CONCLUSIONS The use of radiation protection drapes during transradial coronary procedures is associated with a significantly lower radiation dose to operators, with the pelvic drape more effective than the use of a single arm drape.

Patient radiation exposure in right versus left trans-radial approach for coronary procedures

OBJECTIVES The aim of this study was to compare radiation exposure, assessed by dose-area product (DAP), in right trans-radial approach (RR) versus left trans-radial approach (LR) for coronary procedures. BACKGROUND In LR the catheter course is more similar to trans-femoral approach, thus allowing an easier negotiation of coronary ostia which, in turn, might translate into reduced fluoroscopy time (FT) and radiation exposure as compared to RR. METHODS We retrospectively selected diagnostic and interventional procedures (PCI) performed by RR or LR at our center from May 2009 to May 2014. We only included in the analysis the procedures in which DAP values were available. RESULTS We analyzed 1464 procedures, 1175 of which performed by RR (80.3%) and 289 by LR (19.7%). Median DAP values were significantly higher in RR as compared to LR for diagnostic and interventional procedures (4482 vs. 3540 cGy.cm(2) and 11523 vs. 10086 cGy.cm(2), respectively; p < 0.05). No significant differences were observed in FT and in contrast volume (CV). In the propensity-matched cohort, consisting of 269 procedures for each group, no significant differences between LR and RR were observed in median DAP values for both diagnostic and interventional procedures (3990 vs. 3542 cGy.cm(2) and 9964 vs. 10216 cGy.cm(2), respectively; p = ns); FT and CV were also similar. At multiple linear regression analysis laterality of trans-radial approach was not associated with DAP. CONCLUSIONS In an experienced trans-radial center LR is not associated with a reduction in radiation exposure, FT or CV as compared to RR.

Non-invasive prediction of angiographic progression of coronary artery disease by dipyridamole-stress echocardiography.

BackgroundCoronary angiography is the currently accepted standard means for assessing progression of coronary artery disease. A dipyridamole‐echocardiography test (DET) might provide an alternative non‐invasive functional imaging method for this purpose. ObjectiveTo assess whether variations in results of serial DET match variations in angiographic assessments of coronary artery disease. MethodsFrom the Pisa Institute of Clinical Physiology stress‐echocardiography data bank (1983–1998), we selected 60 patients satisfying the inclusion criteria of coronary angiography and DET having each been performed and interpreted twice independently and within 1 week. The second angiographic and stress‐echocardiographic assessment was performed 45 ± 31 months after the initial one. Angiographic progressors were defined a priori as patients with any progression of stenosis to occlusion and those with any stenosis > 30% with > 20% progression of stenosis measured by visual and quantitative coronary angiography. Stress‐echocardiography progressors were defined as those patients who had previously had a negative test of a test having a positive result and those patients who had positive results of tests both in initial testing and in a second session of testing with the latter having a peak wall‐motion‐score index > 0.12 (on a scale of 1, normal to 4, dyskinetic in a 16‐segment model) larger than the former. ResultsOf the 60 patients, 44 were angiographic ‘progressors’ and 16 were ‘non progressors’. Stress‐echocardiographic responses were concordant with angiographic identification for 39 of 44 progressors and 15 of 16 non‐progressors, with an overall concordance of 90%. ConclusionsMeasurement of dipyridamole‐stress‐echocardiographic response allows one to separate angiographic progressors and non‐progressors efficiently, simply by taking into account the presence, extent and severity of stress‐induced abnormalities of wall motion.