Best Practices for the Prevention of Radial Artery Occlusion After Transradial Diagnostic Angiography and Intervention: An International Consensus Paper.

Transradial access (TRA) is increasingly used worldwide for percutaneous interventional procedures and associated with lower bleeding and vascular complications than transfemoral artery access. Radial artery occlusion (RAO) is the most frequent post-procedural complication of TRA, restricting the use of the same radial artery for future procedures and as a conduit for coronary artery bypass graft. The authors review recent advances in the prevention of RAO following percutaneous TRA diagnostic or interventional procedures. Based on the available data, the authors provide easily applicable and effective recommendations to prevent periprocedural RAO and maximize the chances of access in case of repeat catheterization or coronary artery bypass grafting surgery.

Prognostic role of multiple biomarkers in stable patients undergoing fractional flow reserve-guided coronary angioplasty.

AIMS: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI), along with optimal medical therapy, improves clinical outcome by targeting ischemia-inducing stenosis. Yet, plaque progression or stent failure may cause recurring cardiac events. We assessed the potential prognostic role of different inflammatory biomarkers, known to be associated with plaque progression or stent failure, in patients undergoing FFR-guided PCI. METHODS: We prospectively enrolled 169 stable angina patients with intermediate coronary stenosis at angiography undergoing FFR-guided PCI. PCI was performed if FFR was 0.80 or less, deferred if FFR was more than 0.80. Serum baseline levels of high-sensitivity C-reactive protein (hs-CRP), eosinophil cationic protein (ECP), cystatin-C (Cys-C), and thromboxane A2 (TXA2) were assessed. Rate of major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, recurrent myocardial infarction, and target vessel revascularization (TVR), was evaluated. RESULTS: PCI was performed in 78 patients (46%) (mean age 69 ±â€Š10 years, men 73%) and deferred in 91 patients (54%) (mean age 64 ±â€Š11 years, men 53%). Mean clinical follow-up was 31 ±â€Š11 months. Within the PCI group, patients with MACE (n = 14 [18%]) had significantly higher ECP levels than those without (14.4 [9.3-19.5] vs. 4.9 [2.8-10.9] mg/l, P < 0.001), and ECP was a significant predictor of MACE (hazard ratio: 1.05, 95% confidence interval [1.01-1.09], P = 0.021). Within the deferred group, patients with MACE (n = 8 [9%]) had significantly higher CRP levels than those without (15 [6.5-31.9] vs. 1.6 [0.9-2.9] mg/l, P < 0.001) and CRP was a significant predictor of MACE (hazard ratio: 1.04, 95% confidence interval [1.01-1.07], P = 0.015). Cys-C and TXA2 were not significantly different between the two groups. CONCLUSION: Assessing inflammatory biomarkers allows the identification of patients remaining at residual higher risk of MACE after FFR-guided PCI.

[Intracardiac echography in interventional cardiology]. / L'ecografia intracardiaca in cardiologia interventistica.

Since its early development, interventional cardiology relies on radiological imaging to show and describe vascular structures involved in percutaneous treatment. However, the development of the transcatheter approach to structural heart disease has highlighted the limits of X-rays in guiding interventions targeting soft heart tissues because of their low radiological resolution. Transesophageal echocardiography has thus gained an important role in many catheterization laboratories that perform percutaneous structural heart disease interventions. The endorsement of this technique necessarily requires expertise of echocardiographers and anesthesiologists for endotracheal intubation, thus increasing the logistic complexity of the procedure. Hence, the idea to apply ultrasonography directly into the heart, thus the introduction of intracardiac echography. At present, there are two different technological implementations of intracardiac echography related to the use of an electronic or mechanical ultrasonic transducer placed at the tip of a catheter inserted into the cardiac chambers, most frequently via femoral venous vascular access. In this review, we describe the potentials, advantages and limits of intracardiac echography, as well as its operative function, current use, and future developments.

A randomized multicenter study comparing a paclitaxel drug-eluting balloon with a paclitaxel-eluting stent in small coronary vessels: the BELLO (Balloon Elution and Late Loss Optimization) study.

OBJECTIVES: The aim of this study was to evaluate the efficacy of drug-eluting balloons (DEB) compared with paclitaxel-eluting stents (PES) for the reduction of restenosis in small vessels. BACKGROUND: DEB have been shown to be effective in the treatment of coronary in-stent restenosis, but data are limited regarding their efficacy in de novo disease. METHODS: BELLO (Balloon Elution and Late Loss Optimization) is a prospective, multicenter trial that randomized 182 patients with lesions located in small vessels (reference diameter <2.8 mm) to treatment with paclitaxel DEB and provisional bare-metal stenting (n = 90) or PES implantation (n = 92). The primary endpoint was noninferiority of angiographic in-stent (in-balloon) late loss with a delta of 0.25 mm. Secondary endpoints were angiographic restenosis, target lesion revascularization, and major adverse cardiac events (MACE; death, myocardial infarction, target vessel revascularization) at 6 months. RESULTS: Baseline characteristics were well matched, except for a smaller vessel size in the DEB group (2.15 ± 0.27 mm vs. 2.25 ± 0.24 mm; p = 0.003). The majority (89%) of lesions involved vessels with a diameter <2.5 mm. Bailout stenting was required in 20% of lesions in the DEB group. The primary endpoint of in-stent (in-balloon) late loss was significantly less with DEB compared with PES (0.08 ± 0.38 mm vs. 0.29 ± 0.44 mm; difference -0.21; 95% CI: -0.34 to -0.09; p(noninferiority) < 0.001; p(superiority) = 0.001). At 6 months, DEB and PES were associated with similar rates of angiographic restenosis (10% vs. 14.6%; p = 0.35), [corrected] target lesion revascularization (4.4% vs. 7.6%; p = 0.37), and MACE (10% vs. 16.3%; p = 0.21). [corrected]. CONCLUSIONS: Treatment of small-vessel disease with a paclitaxel DEB was associated with less angiographic late loss and similar rates of restenosis and revascularization as a PES. (Balloon Elution and Late Loss Optimization [BELLO]; Study NCT01086579).

Ticagrelor in ST-elevation myocardial infarction.

Ticagrelor is a new oral antagonist of the platelet P2Y12 receptor that offers several potential advantages compared to clopidogrel including faster and more effective inhibition of platelet aggregation. Ticagrelor has been compared to clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial in a broad population of patients with acute coronary syndrome showing a reduction of the 12-month risk of death from vascular causes, myocardial infarction and stroke without increasing the overall risk of major bleeding. In a subanalysis of the PLATO trial focusing on patients with ST-elevation myocardial infarction, ticagrelor results were consistent with those of the overall trial. Additionally, possible pleiotropic effects of ticagrelor, including an appealing interaction with adenosine, might constitute a specific advantage in this particular subset of patients.

Inflammation-related effects of adjuvant influenza A vaccination on platelet activation and cardiac autonomic function.

BACKGROUND: Inflammation, platelet reactivity and cardiac autonomic dysfunction increase the risk of cardiovascular events, but the relationships between these prognostic markers are poorly defined. In this study, we investigated the effect of an inflammatory stimulus (influenza A vaccine) on platelet activation and cardiac autonomic function. METHODS: We measured serum C-reactive protein (CRP) and interleukin-6 levels, monocyte-platelet aggregates (MPAs) and monocyte/platelet receptor expression before and after adjuvant influenza A vaccination in 28 patients with type II diabetes (mean age 62.1 ± 8 years, 18 men). Twenty-four-hour Holter electrocardiogram was recorded 24 h before and after vaccination; heart rate variability (HRV) was assessed as a measure of cardiac autonomic function. RESULTS: Inflammatory cytokines, MPA formation and monocyte/platelet receptor expression increased after vaccination. CRP was 2.6 ± 2.8 and 7.1 ± 5.7 mg L⁻¹ 48 h before and after vaccination, respectively (P < 0.0001). HRV parameters decreased after vaccination compared to baseline, with very low-frequency amplitude showing the most significant change (34.6 ± 11.8 and 31.0 ± 10.2 ms 48 h before and after vaccination, respectively; P = 0.002). A significant correlation was found between percentage changes in CRP levels and in most HRV variables, with the most significant correlations between changes in CRP levels and changes in standard deviation of all normal RR intervals (r = 0.43; P = 0.02). CONCLUSIONS: Together with an inflammatory reaction, influenza A vaccine induced platelet activation and sympathovagal imbalance towards adrenergic predominance. Significant correlations were found between CRP levels and HRV parameters, suggesting a pathophysiological link between inflammation and cardiac autonomic regulation. The vaccine-related platelet activation and cardiac autonomic dysfunction may transiently increase the risk of cardiovascular events.

Long-term prognosis of patients with cardiac syndrome X.

BACKGROUND: Previous follow-up studies of patients with cardiac syndrome X (CSX) reported good prognosis. However, some recent reports challenged this finding by showing appreciable mortality rates in patients with angina and normal coronary arteries admitted for acute coronary syndromes. METHODS: We performed clinical follow-up of 155 patients (mean age 58.9+/-10 years, 40 men) with typical CSX. The occurrence of major cardiac events (cardiac death, acute myocardial infarction), readmission for chest pain, revascularization procedures, angina status, and non cardiac events during follow-up were collected for each patient. RESULTS: At a mean follow-up time of 137+/-78 months (range 24-372) from the onset of symptoms, 4 patients died, 3 for cancers and 1 for acute pancreatitis. No patient died from cardiovascular causes or had any major cardiovascular event. Hospital readmission for recurrent chest pain was reported by 89 patients (58%), and 33 (22%) underwent at least one more coronary angiography. During follow-up, chest pain had remained unchanged in 33% of patients and had worsened in 14% of patients. CONCLUSION: Our data show that patients with CSX have excellent long-term clinical prognosis. A significant number of patients, however, shows persistence or worsening of symptoms, as well as further recurrence to medical evaluation.

Predictors of exercise-induced platelet reactivity in patients with chronic stable angina.

OBJECTIVE: Previous studies have shown that exercise increases platelet reactivity in patients with coronary artery disease (CAD). However, the response of platelet reactivity to exercise is considerably variable and its predictors are poorly known. METHODS: We studied 214 consecutive patients (age 61.9 +/- 9 years, 167 men) with stable angina and obstructive coronary artery disease. All patients underwent a symptom-limited treadmill exercise stress test. Venous blood samples were collected before and at peak exercise. Platelet reactivity was assessed by the platelet function analyzer system as the time for flowing whole blood to occlude a collagen-adenosine diphosphate ring (closure time: shorter times = higher reactivity). Both closure time at peak exercise and the exercise-induced change in closure time from rest were assessed as an expression of exercise-related platelet reactivity. RESULTS: Closure time decreased significantly with exercise in the whole population (from 95.9 +/- 22 to 81.2 +/- 18 s, P < 0.001). The only variable significantly associated with closure time at peak exercise was hematocrit (P = 0.003). Basal systolic blood pressure (P = 0.023) and lack of nitrate use (P = 0.03), on the contrary, were the only variables significantly associated with increased exercise-induced closure time change. Peak hematocrit maintained an independent association with peak closure time in multivariable analysis, although the correlation was mild. No variable, on the contrary, was associated with exercise-induced platelet reactivity after correction for basal closure time values at multivariable analyses. CONCLUSION: Among stable coronary artery disease patients, platelet reactivity after exercise cannot be reliably predicted by several common clinical and laboratory variables.

Relation between stress-induced myocardial perfusion defects on cardiovascular magnetic resonance and coronary microvascular dysfunction in patients with cardiac syndrome X.

OBJECTIVES: The purpose of this study was to investigate whether a direct relation can be demonstrated between myocardial perfusion defects detected during dobutamine stress test (DST) by cardiovascular magnetic resonance (CMR) and impairment of coronary microvascular dilatory function in patients with cardiac syndrome X (CSX). BACKGROUND: Despite the fact that coronary microvascular dysfunction has been shown in most patients with CSX, the ischemic origin of CSX remains debated. No previous study assessed whether a strict relation exists between abnormalities in myocardial perfusion and coronary microvascular dysfunction in CSX patients. METHODS: Eighteen CSX patients (mean age 58 +/- 7 years, 7 men) and 10 healthy control subjects (mean age 54 +/- 8 years, 4 men) underwent myocardial perfusion study by gadolinium-enhanced CMR at rest and at peak DST (maximal dose 40 microg/kg/min). Coronary flow response (CFR) to adenosine (140 microg/kg/min in 90 s) in the left anterior descending (LAD) coronary artery was assessed by high-resolution transthoracic echo-Doppler and expressed as the ratio between coronary flow velocity at peak adenosine and at rest. RESULTS: At peak DST, reversible perfusion defects on CMR were found in 10 CSX patients (56%) but in none of the control subjects (p = 0.004). The CFR to adenosine in the LAD coronary artery was lower in CSX patients than in control subjects (2.03 +/- 0.63 vs. 3.29 +/- 1.0, p = 0.0004). The CSX patients with DST-induced myocardial perfusion defects in the LAD territory on CMR had a lower CFR to adenosine compared with those without perfusion defects in the LAD territory (1.69 +/- 0.5 vs. 2.31 +/- 0.6, p = 0.01). A significant correlation was found in CSX patients between CFR to adenosine and a DST perfusion defect score on CMR in the LAD territory (r = -0.45, p = 0.019). CONCLUSIONS: Our data concurrently show DST-induced myocardial perfusion defects on CMR and reduced CFR in the LAD coronary artery territory in CSX patients, thus giving strong evidence that a dysfunction of coronary microcirculation resulting in myocardial perfusion abnormalities is present in these patients.

Noninvasive evaluation of flow reserve in the left anterior descending coronary artery in patients with cardiac syndrome X.

Data on coronary flow reserve (CFR) in patients with syndrome X are still controversial. Further, noninvasive evaluation of epicardial and microvascular flow reserves in these patients has never been performed. In 17 patients with syndrome X and in 17 age- and gender-matched control subjects, CFR in the mid left anterior descending coronary artery (LAD) was evaluated by transthoracic color and pulse-wave Doppler using a 7-mHz probe (Sequoia, Siemens). Peak diastolic LAD flow was calculated at rest and at peak adenosine (140 microg/kg/min intravenously in 90 seconds). Myocardial contrast echocardiography (MCE) was performed at rest and during adenosine use by real-time cadence pulse sequencing and intravenous SonoVue (Bracco; 5 ml at 1 ml/min) and microvascular blood volume (A), velocity (beta), and flow (Axbeta) by replenishing curves (y = A[1 - e(betat)]). CFR was measured by Doppler echocardiography as an adenosine/rest velocity ratio and by MCE as a microvascular volume, velocity, and flow adenosine/rest ratio. Compared with controls, patients with syndrome X demonstrated lower LAD CFR and velocity and flow microvascular flow reserves (p <0.01, <0.005, and <0.005, respectively). In patients with syndrome X, those with angina and ST-segment depression during adenosine testing had even lower LAD CFR and velocity and flow microvascular flow reserves compared with those with no symptoms (p <0.0001, <0.0001, and <0.005, respectively). LAD CFR demonstrated a significant linear correlation with velocity microvascular flow reserve (r = 0.92, p <0.0001) and flow microvascular flow reserve (r = 0.77, p <0.0001). In conclusion, CFR in the LAD, successfully evaluated by transthoracic Doppler echocardiography and MCE, is significantly decreased in patients with syndrome X and even more in those with angina pectoris and ST-segment depression during adenosine testing. Thus, noninvasive evaluation of CFR by echocardiography is feasible and provides information on the severity of microvascular impairment.

Relationship between changes in platelet reactivity and changes in platelet receptor expression induced by physical exercise.

INTRODUCTION: In previous studies we have consistently shown a significant increase of platelet reactivity after exercise in patients with obstructive coronary artery disease (CAD). We also observed a significant individual variability in the response to exercise of platelet reactivity in these patients. Whether exercise-induced changes in platelet reactivity correlate with changes in platelet membrane receptors in patients with CAD is unknown. METHODS: We studied 26 patients with stable CAD and 10 matched healthy controls who underwent a symptom-limited treadmill exercise stress test. Venous blood samples were collected at rest and within 5 min of peak exercise. Platelet reactivity was measured by the PFA-100 method as time to occlude (closure time, CT) a ring coated with collagen/adenosine diphosphate (C/ADP). Platelet expression of glycoprotein (GP) IIb/IIIa, in both global (CD41) and active form (PAC-1), and P-selectin (CD62P) and formation of leukocyte-platelet aggregates were assessed by flow cytometry. RESULTS: After exercise CT did not change in controls (85.4+/-12 to 84.0+/-9 s, p=0.37), whereas it decreased in CAD patients (98.8+/-24 to 91.4+/-25 s, p<0.001). After exercise, CD41 and PAC-1 platelet expression increased significantly in CAD patients (p=0.04 for both), but not in controls (p=0.39 and p=0.98, respectively). To evaluate the relationship between the response to exercise of platelet reactivity and of platelet receptor expression, CAD patients were divided into two groups: CAD group 1 (16 patients, decrease in CT >5 s after exercise) and CAD group 2 (10 patients no increase in platelet reactivity after exercise). CD41 and PAC-1 expression increased in CAD group 1 (p=0.008 and p=0.026, respectively) but not in CAD group 2 (p=0.39 and p=0.50, respectively). No significant differences were observed between the 2 groups for changes in CD62P and leukocyte-platelet aggregates. CONCLUSIONS: Our data show that, in patients with stable CAD, an increased platelet reactivity to C/ADP stimulation after exercise, as assessed by the PFA-100 method, is specifically associated with an increased expression of platelet GP IIb/IIIa receptor.