Domenico Grieco

High Versus Standard Clopidogrel Maintenance Dose After Percutaneous Coronary Intervention and Effects on Platelet Inhibition, Endothelial Function, and Inflammation : Results of the ARMYDA-150 mg (Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty) Randomized Study

OBJECTIVES This study was done to compare effects of high versus standard clopidogrel maintenance doses on platelet inhibition, inflammation, and endothelial function in patients undergoing percutaneous coronary intervention. BACKGROUND Previous data suggested that clopidogrel has various biological actions in addition to antiplatelet effects. METHODS Fifty patients were randomly assigned 1 month after intervention (T-0) to receive standard (75 mg/day; n = 25) or high (150 mg/day; n = 25) clopidogrel maintenance dose for 30 days (until T-1); at this time-point, cross-over was performed, and the assigned clopidogrel maintenance regimen was switched and continued for a further 30 days (until T-2). Platelet reactivity (expressed as P2Y(12) reaction units by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]), endothelial function (evaluated by flow-mediated vasodilation), and high-sensitivity C-reactive protein levels were measured at T-0, T-1, and T-2. RESULTS Patients in the 150-mg/day arm had higher platelet inhibition (50 ± 20% vs. 31 ± 20% in the 75-mg/day group; p < 0.0001), better flow-mediated vasodilation (16.9 ± 12.6% vs. 7.9 ± 7.5%; p = 0.0001), and lower high-sensitivity C-reactive protein levels (3.6 ± 3.0 mg/l vs. 7.0 ± 8.6 mg/l; p = 0.016). Higher clopidogrel dose was associated with decreased proportion of patients with P2Y(12) reaction units ≥ 240 (12% vs. 32%; p = 0.001), flow-mediated vasodilation <7% (16% vs. 58%; p = 0.0003), and high-sensitivity C-reactive protein levels >3 mg/l (46% vs. 64%; p = 0.07). CONCLUSIONS For patients undergoing percutaneous coronary intervention, the 150-mg/day clopidogrel maintenance dose is associated with stronger platelet inhibition, improvement of endothelial function, and reduction of inflammation, compared with the currently recommended 75-mg/day regimen; those effects might have a role in the clinical benefit observed with clopidogrel and may provide the rationale for using the higher maintenance regimen in selected patients.

Effect of High-Dose Atorvastatin Reload on the Release of Endothelial Progenitor Cells in Patients on Long-Term Statin Treatment Who Underwent Percutaneous Coronary Intervention (from the ARMYDA-EPC Study)

Endothelial progenitor cells (EPCs) may concur to endogenous vascular repair. Previous studies have reported that statin treatment increases EPC levels. We investigated whether this occurs in patients on long-term statin treatment who underwent percutaneous coronary interventions (PCIs). In a phase A study, 53 patients (atorvastatin reload [AR] 80 mg 12 hours before + 40 mg 2 hours before PCI, n = 27; placebo [P], n = 26) were evaluated for EPC mobilization as CD45dim/CD34+/CD133+/KDR+ cell number by flow cytometry. Assays were run at randomization (12 hours before PCI, R), immediately before PCI (T0) at 8 (T8) and 24 hours (T24). In phase B study, 50 patients (AR, n = 25; P, n = 25) were evaluated for early colony formation by Hill colony forming unit (CFU) assay, with sampling at randomization and 24 hours later. In phase A, EPCs levels were similar at randomization between 2 arms (0.23% [0.14 to 0.54] of total events in AR vs 0.22% [0.04 to 0.37] in P group; p = 0.33). At PCI, EPC levels were higher in AR arm (0.42% [0.06 to 0.30] vs 0.19% [0.06 to 030]; p = 0.009). Higher EPC levels in AR group were also found at 8 and 24 hours. In phase B, EPC CFUs/well numbers at randomization were similar in the 2 arms (8 [6 to 12] in AR vs 12 [6 to 20] in P group, p = 0.109). EPC CFU/well at 24 hours became significantly higher in AR arm (17 [10 to 23] vs 5 [2 to 13], p = 0.002). In conclusion, high-dose AR before PCI in patients on long-term statin therapy promptly increases EPCs mobilization, which are capable of early colony formation and may contribute to cardioprotection.

Diabetes mellitus and atrial remodelling in patients with paroxysmal atrial fibrillation: Role of electroanatomical mapping and catheter ablation

Complex fractionated atrial electrograms (CFAEs) are related to atrial fibrosis, but their ablation has not yet shown superiority. The aim of the study was to compare, in terms of clinical outcome, two strategies of paroxysmal atrial fibrillation (AF) ablation in patients with type 1 diabetes mellitus (DM): pulmonary vein isolation (PVI) vs. PVI + CFAEs. Compared to an historical population of patient with paroxysmal AF and without DM, a higher percentage of patients with DM showed more than 25% of atrial area interested by CFAEs (study population, 58% vs historical group, 15%; p < 0.05). In PVI group, recurrences rate was similar in patients with HbA1c ⩽ 7.5% vs HbA1c > 7.5% (30% vs 22%; p = not significant), but a greater AF burden was observed in patients with HbA1c > 7.5% (6 ± 2 vs 1 ± 2; p < 0.05). In hazard ratios analysis PVI+CFAEs seems more effective than PVI alone in patients with HbA1c > 7.5% (hazard ratio, 1.28; p < 0.05), more than 25 years from DM diagnosis (hazard ratio, 1.25; p < 0.05) and more than five AF episodes/year (hazard ratio, 1.2; p < 0.05). Type 1 DM patients had complex atrial ‘substrate’, as documented by wider CFAEs areas. Despite this, 1-year follow-up recurrence rate was similar between two ablation approaches (PVI 27% vs. PVI+CFAEs 21%; p = not significant). In our study, only specific subgroups, like patients with disglycaemic state (HbA1c > 7.5%), long diabetes mellitus history and high AF burden, benefit from PVI+ CFAEs approach.

Patients with left bundle branch block and left axis deviation show a specific left ventricular asynchrony pattern: Implications for left ventricular lead placement during CRT implantation

BACKGROUND Left bundle branch block (LBBB) and left axis deviation (LAD) patients may have poor response to resynchronization therapy (CRT). We sought to assess if LBBB and LAD patients show a specific pattern of mechanical asynchrony. METHODS CRT candidates with non-ischemic cardiomyopathy and LBBB were categorized as having normal QRS axis (within -30° and +90°) or LAD (within -30° and -90°). Patients underwent tissue Doppler imaging (TDI) to measure time interval between onset of QRS complex and peak systolic velocity in ejection period (Q-peak) at basal segments of septal, inferior, lateral and anterior walls, as expression of local timing of mechanical activation. RESULTS Thirty patients (mean age 70.6years; 19 males) were included. Mean left ventricular ejection fraction was 0.28±0.06. Mean QRS duration was 172.5±13.9ms. Fifteen patients showed LBBB with LAD (QRS duration 173±14; EF 0.27±0.06). The other 15 patients had LBBB with a normal QRS axis (QRS duration 172±14; EF 0.29±0.05). Among patients with LAD, Q-peak interval was significantly longer at the anterior wall in comparison to each other walls (septal 201±46ms, inferior 242±58ms, lateral 267±45ms, anterior 302±50ms; p<0.0001). Conversely, in patients without LAD Q-peak interval was longer at lateral wall, when compared to each other (septal 228±65ms, inferior 250±64ms, lateral 328±98ms, anterior 291±86ms; p<0.0001). CONCLUSIONS Patients with heart failure, presenting LBBB and LAD, show a specific pattern of ventricular asynchrony, with latest activation at anterior wall. This finding could affect target vessel selection during CRT procedures in these patients.

An unusual case of arrhythmic palpitations in a volleyball player

A case of a 31 years old woman volleyball player highly symptomatic for arrhythmic palpitations is reported. The woman was disqualified from competitive sport and referred to our centre for atrial fibrillation (AF) ablation. During symptoms surface ECG had documented irregular supraventricular tachyarrhythmia interpreted as AF. Electrophysiological study could reveal double-His conduction as the true arrhythmia mechanism and the patient was successfully treated with nodal slow pathway ablation. Patient was totally asymptomatic at a 12 months follow up and he was readmitted to competitive sport. The case further underlines the concept that young subjects with suspected lone AF should undergo to a careful clinical evaluation in order to reconstruct the exact electrophysiological mechanism to plan a safe and effective therapy.

Safety and feasibility of atrial fibrillation ablation using Amigo® system versus manual approach: A pilot study

Background The Amigo® Remote Catheter System is a relatively new robotic system for catheter navigation. This study compared feasibility and safety using Amigo (RCM) versus manual catheter manipulation (MCM) to treat paroxysmal atrial fibrillation (PAF). Contact force (CF) and force-time integral (FTI) values obtained during pulmonary vein isolation (PVI) ablation were compared. Methods Forty patients were randomly selected for either RCM (20) or MCM (20). All were studied with the Thermocool® SmartTouch® force-sensing catheter (STc). Contact Force (CF), Force Time Integral (FTI) and procedure-related data, were measured/stored in the CARTO®3. Results All cases achieved complete PVI without major complications. Mean CF was significantly higher in the RCM group (13.3 ± 7.7 g in RCM vs. 12.04 ± 7.42 g in MCM p < 0.001), as was overall mean FTI (425.6 gs ± 199.6 gs with RCM and 407.5 gs ± 288.0 gs in MCM (p = 0.007) and was more likely to fall into the optimal FTI range (400-1000) using RCM (66.1% versus 49.1%, p < 0.001). FTI was significantly more likely to fall within the optimal range in each PV, as was CF within its optimal range in the right PVs, but trended higher in the left PVs. Freedom from atrial tachyarrhythmia was 90.0% for the RCM and 70.0% for the MCM group (p = 0,12) at 540 days follow-up. Conclusions This pilot study suggests that use of the Amigo RCM system, with STc catheter, seems to be safe and effective for PVI ablation in paroxysmal AF patients. A not statistically significant favorable trend was observed for RCM in term of AF-free survival.

Carotid sinus hypersensitivity syncope: is there a possiblealternative approach to pacemaker implantation in youngpatients?

Carotid sinus hypersensitivity (CSH) is frequently found in about one third of elderly patients with syncope and trauma, but it may also be a common finding in younger patients. Pacemaker implantation is recommended in patients with recurrent syncope once CSH has been recognised. Cardioneuroablation (CNA) has been reported as an effective treatment in cardioinhibitory syncope [1, 2]. A few reports are currently available in neurally mediated syncope and functional atrioventricular block [3, 4], but no previous experiences are available in carotid sinus hypersensitivity syncope. A 42-year-old female patient, with normal heart and no relevant medical history, was referred to our centre for recurrent CSH syncope. As the patient refused PM implantation, autonomic nervous system modulation through CNA was proposed. At the basic EP study normal atrioventricular conduction parameters (AH 68 ms, HV 50 ms) were documented; during CSM a sinus arrest of up to 5.4 s occurred. Electroanatomical mapping of the right atrium with identification of phrenic nerve course was performed (Figure 1 A). Anterior right CNA (35 W, 43°C, 2 min and 40 s of RF delivery) at the level of the septal aspect of the superior vena cava determined a shortening of the basal sinus cycle length (from 975 ms to 730 ms). Vagal stimulation by manual CSM did not cause any pause. After 20 min, a new CSM showed suprahisian atrioventricular block with normal HV (RR max of 2608 ms) (Figure 1 B). Inferior right CNA (35 W, 43°C, 1 min and 30 s of RF delivery) posterior to the coronary sinus ostium was performed, in a region previously reported to be involved in AV conduction neuromodulation (located between the inferior vena cava and the right/left atrium) [1–3]. At CSM after RF and after 30 min of observation no longer pathological pauses were documented (RR max 1.4 s). Shorter AV conduction intervals were observed (AH 48 ms, HV 50 ms). At 6-month follow-up the patient is still asymptomatic for syncope and dizziness. Ablation lesions were performed using an anatomical approach (without AF-Nest mapping); no pharmacological test was performed to confirm the denervation; only right atrial CNA was performed in order to minimize the risk of complications; a longer follow-up period is needed to confirm ablation results. The CNA restricted to the right atrium, if properly standardized, could be an attractive and safer alternative to PM implantation to treat CSH syncope, especially in younger patients who are more vulnerable to mediumand long-term complications related to device implantation.