Three-dimensional guided selective right ventricular septal pacing preserves ventricular systolic function and synchrony in pediatric patients.

BACKGROUND: Nonfluoroscopic 3-dimensional (3D) electroanatomic mapping systems (EAMs) have been developed to guide cardiac catheter navigation and reduce fluoroscopy. Selective right ventricular (RV) septal pacing could prevent pacing-induced left ventricular (LV) dysfunction. OBJECTIVE: The purpose of this study was to determine whether EAM-guided selective RV septal pacing preserves LV contractility/synchrony in pediatric patients with complete atrioventricular block (CAVB) and no other congenital heart defects. METHODS: Prospective analysis of children/adolescents who underwent EAM-guided selective RV pacing was performed. A 3D pacing map guided ventricular lead implantation at septal sites with narrow paced QRS. Serial echocardiograms were obtained after pacemaker implantation to monitor for function (volumes, ejection fraction [EF], global longitudinal/circumferential strain) and synchrony (interventricular mechanical delay, septal to posterior wall motion delay, systolic dyssynchrony index). Data are reported as median (25th-75th percentile). RESULTS: Thirty-two CAVB patients (age 9.8 [7.0-14.0] years; 11 with a previous pacing system) underwent selective RV septal pacing (13 DDD, 19 VVIR pacemaker; midseptum 22, parahisian 7, RV outflow tract 3) with narrow paced QRS (110 [100-120] ms) and low radiation exposure. Follow-up over 24 (5-33) months showed preserved LV function and synchrony, without significant differences between pacing sites (midseptum-parahisian) and mode (VVIR-DDD). EF decreased after implantation in patients without previous pacing, although values were mainly within normal limits. Three parahisian patients underwent early lead repositioning. CONCLUSION: EAM-guided selective RV septal pacing is a feasible technique associated with preserved LV systolic function and synchrony and low radiation exposure in pediatric patients with CAVB.

Low-voltage bridge strategy to guide cryoablation of typical and atypical atrioventricular nodal re-entry tachycardia in children: mid-term outcomes in a large cohort of patients.

AIMS: In the current literature, results of the low-voltage bridge (LVB) ablation strategy for the definitive treatment of atrioventricular nodal re-entry tachycardia (AVNRT) seem to be encouraging also in children. The aims of this study were (i) to prospectively evaluate the mid-term efficacy of LVB ablation in a very large cohort of children with AVNRT, and (ii) to identify electrophysiological factors associated with recurrence. METHODS AND RESULTS: One hundred and eighty-four children (42% male, mean age 13 ± 4 years) with AVNRT underwent transcatheter cryoablation guided by voltage mapping of the Koch's triangle. Acute procedural success was 99.2% in children showing AVNRT inducibility at the electrophysiological study. The overall recurrence rate was 2.7%. The presence of two LVBs, a longer fluoroscopy time and the presence of both typical and atypical AVNRT, were found to be significantly associated with an increased recurrence rate during mid-term follow-up. Conversely, there was no significant association between recurrences and patient's age, type of LVB, lesion length, number of cryolesions or catheter tip size. CONCLUSION: The LVB ablation strategy is very effective in AVNRT treatment in children. Recurrences are related to the complexity of the arrhythmogenic substrate.

Electroanatomic mapping-guided localization of alternative right ventricular septal pacing sites in children.

BACKGROUND: Alternative right ventricular (RV) sites (RVAPS) have been proposed to prevent or reduce RV pacing-induced left-ventricular (LV) dysfunction. Nonfluoroscopic 3D electroanatomic mapping systems (EAM) have been developed to guide cardiac catheter navigation and reduce fluoroscopy during electrophysiological procedures or pacemaker implantations. AIM: The aim of the study was to compare the results of EAM-guided permanent pacemaker implantation aiming at RVAPS with conventional fluoroscopic-guided implantation in RV apex (RVA) in children and adolescents. METHODS: A prospective, randomized analysis was performed on children/adolescents with complete atrioventricular block (CAVB) who underwent EAM-guided pacemaker and transvenous leads implantation into RVAPS (EAM-RVAPS) or conventional, fluoroscopic-guided implantation into RV apex (RVA). In EAM-RVAPS, a pacing map guided the implantation of ventricular leads in septal sites with narrower QRS. After implantation, LV contractility (ejection fraction [EF], Global Longitudinal Strain [GLS]) and synchrony were evaluated at 1-12 months. RESULTS: Twenty-one pediatric patients with CAVB, with (six patients) or without structural heart diseases, aged 4-16 (median 10.5) years, were divided in two groups: EAM-RVAPS (11 patients, four dual-chamber/DDD, seven single-chamber/VVIR pacemakers) and RVA (10 patients, one DDD/nine VVIR). The two groups did not show significant differences for preoperative parameters. EAM-RVAPS showed: preserved LVEF and synchrony (not significantly different than RVA), significantly lower GLS and radiation doses/exposures, in spite more complex procedures, significantly longer procedure times and narrower paced QRS than RVA. CONCLUSIONS: EAM-guided procedures have been useful to reduce radiation exposure and to localize RVAPS with narrower paced QRS and lower GLS than RVA.

Physiological pacing in young patients with complex congenital heart defects.

AIM: Young patients with operated complex congenital heart defects (CHD) often develop sinus node dysfunction (SND) requiring permanent pacing with rate-responsive function. Activity-driven sensors cannot account for nonmovement stress and cannot modulate heart rate physiologically. Closed Loop Stimulation (CLS, Biotronik, Berlin, Germany) is a physiological rate-responsive pacemaker based on the indirect measure of ventricular contractility. No data are available on the effects of such pacing strategy in young patients. METHODS: We report a series of nine patients with CHD and SND who underwent single-chamber CLS-atrial pacing with endocardial or epicardial lead. During the first 30 days, the pacemaker was programmed in AAI pacing mode and then was switched to CLS-atrial pacing mode. An in-hospital control was scheduled 1-2 months later to evaluate the CLS response to neurovegetative stresses (i.e., nonmovement stress [Stroop color test, handgrip] and exercise stress test) and Holter monitor. CLS pacing was compared with rate-responsive accelerometer-driven pacing (AAIR). RESULTS: At telemetric interrogation, CLS pacing showed a more physiological pattern of 24-h heart rate trends than accelerometer sensors. The data obtained during nonmovement/exercise stress demonstrated a physiological increase in the pacing rate with CLS, in synergy with spontaneous events. The accelerometer sensor histogram, during nonmovement stress, showed a "nonresponse" behavior (only lower rate events), and during exercise test showed most events in lower rate range. Holter monitoring showed increase of average and maximum heart rate compared with AAIR. CONCLUSION: In young CHD patients, endocardial/epicardial CLS-atrial pacing demonstrated a physiological response of heart rate to neurovegetative and physical stresses.

Subcutaneous implantable cardioverter-defibrillator: is it ready for use in children and young adults? A single-centre study.

Aims: Use of the subcutaneous implantable cardioverter-defibrillator (S-ICD) to prevent sudden cardiac death is increasing. Few data exist on S-ICD in young patients. We reviewed our single-centre experience in order to assess the effectiveness and safety of S-ICD implantation, and to identify potential factors associated with complications. Methods and results: Observational, non-randomized, standard-of-care study on S-ICD implantation/follow-up in young patients with inherited arrhythmias (IA), cardiomyopathies, and congenital heart defects (CHD). Fifteen patients (6 CHD, 8 cardiomyopathies, and 1 IA), median age 15 years (25th-75th centiles, 14-28), 10 of them <18 years, with body mass index (BMI) 22.6 ± 3.4, underwent S-ICD implantation (primary prevention 93%). The first six patients underwent a standard implantation procedure (three surgical incisions), the following nine a two-incision procedure. No intraoperative complications occurred. Over 12 (7-24) months follow-up, two patients received appropriate shocks and one (7%) inappropriate shock. Four patients had device-related complications requiring surgical intervention: three skin erosions at the superior parasternal incision, one pocket infection. A higher risk of complications was seen in patients who underwent standard procedures [hazard ratio (HR) 4.98, 95% confidence interval (CI) 1.53-47.36; P = 0.0482] and those with BMI <20 (HR 9.44, 95% CI 0.95-93.23; P = 0.0169). Conclusion: S-ICD implantation was safe and effective in young patients with low rates of inappropriate shock. However, the risk of device-related complications during follow-up remains substantial in patients with low BMI. To prevent possible complications, a two-incision technique should be preferred.

Neonatal and Pediatric Arrhythmias: Clinical and Electrocardiographic Aspects.

Arrhythmias have acquired a specific identity in pediatric cardiology, but for pediatric cardiologists it has always been difficult to recognize and treat them. Changes in anatomy and physiology result in electrocardiogram features that differ from the normal adult pattern and vary according to the age of the child. Sinus arrhythmia, ectopic atrial rhythm, "wandering pacemaker," and junctional rhythm can be normal characteristics in children (15%-25% of healthy children can have these rhythms on the electrocardiogram). Tachyarrhythmias and bradyarrhythmias must be treated according to the severity of symptoms, and the patient's age and weight.

Voltage gradient mapping and electrophysiologically guided cryoablation in children with AVNRT.

Aims: Recently, voltage gradient mapping of Koch's triangle to find low-voltage connections, or 'voltage bridges', corresponding to the anatomic position of the slow pathway, has been introduced as a method to ablate atrioventricular nodal reentry tachycardia (AVNRT) in children. Thus, we aimed to assess the effectiveness of voltage mapping of Koch's triangle, combined with the search for the slow potential signal in 'low-voltage bridges', to guide cryoablation of AVNRT in children. Methods and results: From June 2015 to May 2016, 35 consecutive paediatric patients (mean age 12.1 ± 4.5 years) underwent 3D-guided cryoablation of AVNRT at our Institution. Fifteen children were enrolled as control group (mean age 14 ± 4 years). A voltage gradient mapping of Koch's triangle was obtained in all patients, showing low-voltage connections in all children with AVNRT but not in controls. Prior to performing cryoablation, we looked for the typical 'hump and spike' electrogram, generally considered to be representative of slow pathway potential within a low-voltage bridge. In all patients the 'hump and spike' electrogram was found inside bridges of low voltage. Focal or high-density linear lesions, extended or not, were delivered guided by low-voltage bridge visualization. Acute success rate was 100%, and no recurrence was reported at a mean follow-up of 8 ± 3 months. Conclusions: Voltage gradient mapping of Koch's triangle, combined with the search for the slow potential signal in low-voltage bridges, is effective in guiding cryoablation of AVNRT in paediatric patients, with a complete acute success rate and no AVNRT recurrences at mid-term follow-up.

Empirical anticoagulation for patients in sinus rhythm at high risk of ischaemic stroke: A review of current literature.

Ischaemic stroke is one of the commonest causes of morbidity and mortality worldwide and around a fifth of events can be attributed to a cardioembolic source. This is typically due to atrial fibrillation (AF), the most common sustained cardiac arrhythmia. However, AF can, at times, be difficult to detect due to a relative lack of symptoms and the fact that it can be paroxysmal in nature. Studies have shown that diagnosis of AF improves as the length of cardiac monitoring increases. However, prolonged cardiac monitoring is not a cost-effective way of diagnosing AF. Therefore, an alternative approach may be to empirically anticoagulate individuals who are at high risk of stroke. This article summarises current evidence surrounding stroke risk prediction, the use of anticoagulation in the secondary prevention of stroke and its use in the primary prevention of stroke in high risk groups with the aim of determining whether empirical anticoagulation is a safe and effective strategy.

Screening For Atrial Fibrillation In The Community Using A Novel ECG Recorder.

Aims: MyDiagnostick (MDK) is a novel portable ECG recorder. We conducted this study to evaluate its role in screening for atrial fibrillation (AF). Methods: The device is a cylindrical rod with metallic electrodes at both ends recording electrocardiogram (ECG) when both electrodes are held. Individuals were requested to hold the device for approximately 15 s, the device was then connected to a laptop (with proprietary software downloaded) and analysed. Anonymised ECGs were stored for further analysis. A total of 855 ECGs were recorded and analysed offline by two arrhythmia specialists assessing ECG quality, in particular the level of noise. A noise score (NS) was devised regarding ECG quality. Results: Seven individuals were found with unknown AF (0,8%). In general ECG quality was good and rhythm diagnosis was certain with total interobserver agreement. Conclusion: The MDK provided a rapid and accurate rhythm analysis and has potential implications in preventing ischaemic cardio-embolic stroke.

The Need for a Lengthier Cryolesion Can Predict a Worse Outcome in 3D Cryoablation of AV Nodal Slow Pathway in Children.

BACKGROUND: Transcatheter cryoablation is a well-established technique for the treatment of atrioventricular nodal reentry tachycardia (AVNRT) in children. Nevertheless, atrioventricular nodal slow-pathway conduction may recur after an acutely successful procedure. The aim of this study was to evaluate the long-term outcome of acutely successful AVNRT cryoablations in pediatric patients in case of focal cryolesion and in case of need for High-Density Linear Lesion (HDLL) cryoablation due to focal failure. METHODS: Sixty-nine consecutive pediatric patients (30 males, mean age 12.4 ± 3.2 years; range: 5.4-18.0 years) underwent 3D-guided cryoablation for AVNRT at our institution from July 2013 to November 2014. When a focal cryoablation was acutely unsuccessful, a 3D-guided HDLL was created delivering multiple overlapping cryolesions/cryoenergy applications from the ventricular side of the tricuspid annulus to the atrial side, including the site of focal cryoablation if transiently successful. RESULTS: No permanent cryoablation-related complications occurred. Acute success rate was 98.5% (68 out of 69): in 55.9% (38 out of 68) with focal-lesion and in 44.1% (30 out of 68) with HDLL. Mean follow-up was 25.3 months and AVNRT recurrence rate was 13.2% (nine out of 68): 5.2% (two out of 38) with focal lesion and 23.3% (seven out of 30) with HDLL (P = 0.036). CONCLUSIONS: In cryoablation of AVNRT in children, the need for a more aggressive protocol (HDLL), due to the failure of focal ablation, is strictly related to higher recurrence rates. Indeed, AVNRT recurrences after cryoablation in children seem to be due to a larger and deeper substrate rather than due to the type of energy used.

Sex differences in mechanisms, presentation and management of ischaemic heart disease.

Ischaemic heart disease (IHD) is the leading cause of death in women as in men, although presentation in women is on average 7-10 years later. Recent temporal trends show declining IHD incidence and mortality among men but not among women. Other gender differences concern the prevalence of underlying mechanisms. Women more frequently than men have nonobstructive epicardial artery disease, nonatherosclerotic spontaneous coronary artery dissection, stress cardiomyopathy, plaque erosion, microvascular dysfunction, and a heavier risk factor burden, even after adjustment for age. Atypical symptoms of IHD are more common in women. The crude outcomes of both chronic and acute coronary syndromes are worse in women than in men, in relation to older age and comorbidities. After adjustments, in-hospital mortality after acute myocardial infarction is reported to remain higher among younger women compared to male peers. Such female vulnerability, in apparent contrast with the delayed average onset and lesser extent of epicardial atherosclerosis, likely reflects gender differences in early presentation, as well as in mechanisms, prevention, diagnosis, comorbidities, management, and response to treatment. Recognition and quality of care of IHD are still not the same for women and men.

Endothelial and platelet function in children with previous Kawasaki disease.

We investigated whether children with a previous Kawasaki disease (KD) have evidence of abnormal vascular and/or platelet function. We included 14 patients with previous KD and 14 matched controls. We assessed endothelial function by flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), coronary microvascular function by coronary blood flow response (CBFR) to cold pressor test, and platelet reactivity by measuring monocyte-platelet aggregates (MPAs) and CD41-platelet expression by flow cytometry. No differences were found between the groups in FMD, cIMT, or CBFR to cold pressor test. The MPAs were similar in patients with KD and controls. CD41-platelet expression, however, was significantly increased in patients with KD compared with controls, both at rest (14.3 ± 1.9 vs 12.4 ± 1.9 mean fluorescence intensity [mfi], P = .01) and after adenosine diphosphate stimulation (19.3 ± 1.3 vs 17 ± 1.7 mfi, P < .001). In conclusion, children with a previous episode of KD showed increased platelet activation, compared with healthy participants despite no apparent vascular abnormality at follow-up.

Prognostic role of heart rate variability in patients with ST-segment elevation acute myocardial infarction treated by primary angioplasty.

OBJECTIVES: The aim of our study was to assess the prognostic value of heart rate variability (HRV) in ST-segment elevation acute myocardial infarction (STEMI) patients treated by percutaneous transluminal coronary angioplasty (PTCA) and optimal medical therapy. METHODS: We enrolled 182 consecutive patients with a first STEMI (59.1 ± 11 years; 82.4% men) treated by primary PTCA. HRV was assessed on 24-hour Holter ECG recordings before discharge and 1 and 6 months after discharge. The primary end point was the occurrence of major clinical events (MCE), defined as death or new acute myocardial infarction (AMI). RESULTS: At a follow-up of 42 ± 23 months, MCE occurred in 14 patients (7.6%; 3 deaths and 11 re-AMIs). HRV parameters before discharge were significantly lower in patients with MCE, with standard deviation of all RR intervals (SDNN) and very low frequency and low frequency (LF) amplitude being the most predictive variables. HRV assessed at follow-up instead did not significantly predict MCE. At multivariate analysis, only SDNN (HR 0.97; p = 0.02) and LF (HR 0.90; p = 0.04) remained significantly associated with MCE. Lower tertile SDNN and LF values were associated with a multivariate HR of 3.91 (p = 0.015) and of 2.92 (p = 0.048), respectively. Similar results were observed considering re-AMI only as the end point. CONCLUSIONS: In STEMI patients treated by PTCA, HRV assessed before discharge was an independent predictor of MCE and re-AMI.

Effect of pre-infarction angina on platelet reactivity in acute myocardial infarction.

BACKGROUND: Previous studies demonstrated that patients with PIA have a smaller infarct and better in-hospital outcome after acute myocardial infarction, than those without angina. This protective effects has been attributed to ischemic preconditioning (PC), to earlier reperfusion after fibrinolysis or its better collateral circulation development. In this study we aimed at assessing platelet reactivity in patients with history of pre-infarction angina (PIA) in the acute phase of ST segment elevation myocardial infarction (STEMI) and 1 month later. METHODS: 85 consecutive patients (63 ± 10.5 years, 60 male) with a first STEMI treated by primary percutaneous coronary intervention (PCI) were studied at admission and 1 month later. Platelet reactivity was evaluated by flow cytometry with and without adenosine diphosphate (ADP) stimulation, by measuring monocyte-platelet aggregates (MPAs) and glycoprotein IIb/IIIa (CD41) expression in the MPA gate, and CD41 and fibrinogen receptor (PAC-1) expression in the platelet gate. RESULTS: MPAs and expression of platelet receptors CD41 and PAC-1 were significantly lower in patients with than patients without PIA, both with and without ADP stimulation. After 1 month, all cytometry variables both with and without ADP stimulation were similar in the two groups. CONCLUSIONS: This study shows, for the first time, that patients with a first STEMI who experience PIA show a lower platelet reactivity as compared with those without history of PIA.

Coronary microvascular dysfunction after elective percutaneous coronary intervention: correlation with exercise stress test results.

OBJECTIVES: We assessed whether exercise stress test (EST) results are related to the presence of coronary microvascular dysfunction (CMVD) in patients undergoing elective percutaneous coronary intervention (PCI). BACKGROUND: Previous studies showed that EST is poorly reliable in predicting restenosis after PCI; some studies also showed CMVD in the territory of the treated vessel. METHODS: We studied 29 patients (age 64 ± 6, 23 M) with stable coronary artery disease and isolated stenosis (>75%) of the left anterior descending (LAD) coronary artery, undergoing successful PCI with stent implantation. EST and assessment of coronary microvascular function were performed 24h, 3 months and 6 months after PCI. Coronary blood flow (CBF) response to adenosine and to cold-pressor test (CPT) was assessed in the LAD coronary artery by transthoracic Doppler echocardiography. RESULTS: Patients with ST-segment depression ≥ 1 mm at EST performed 24h after PCI (n=11, 38%) showed a lower CBF response to adenosine compared to those with negative EST (1.65 ± 0.4 vs. 2.11 ± 0.4, respectively, p=0.003), whereas the difference in CBF response to CPT was not significant (1.44 ± 0.4 vs. 1.64 ± 0.3, respectively; p=0.11). At 3-month and 6-month follow-up a positive EST was found in 12 (41%) and 13 (44%) patients, respectively; patients with positive EST also had lower CBF response to adenosine compared to those with negative EST (3 months: 1.69 ± 0.3 vs. 2.20 ± 0.3, respectively; 6 months: 1.66 ± 0.2 vs. 2.32 ± 0.3, respectively; p<0.001 for both). CONCLUSIONS: Positive EST after elective successful PCI consistently reflects impairment of hyperemic CBF due to CMVD, which persists over a follow-up period of 6 months.

Association of heart rate variability with arrhythmic events in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is associated with an increased risk of sudden cardiac death (SCD). Risk stratification of ARVC/D patients, however, remains an unresolved issue. In this study we investigated whether heart rate variability (HRV) can be helpful in identifying ARVC/D patients with increased risk of arrhythmic events. METHODS AND RESULTS: We studied 30 consecutive patients (17 males; 45.4 ± 18 years) with ARVC/D, diagnosed according to guideline criteria; 15 patients (50%) had received an implantable cardioverter defibrillator (ICD) for primary SCD prevention. HRV was assessed on 24-h ECG Holter monitoring. The primary endpoint was the occurrence of major arrhythmic events (SCD, sustained ventricular tachycardia (VT), ICD therapy for sustained VT or ventricular fibrillation (VF)). During the follow-up period (19 ± 7 months), no deaths occurred, but 5 patients (17%) experienced arrhythmic events (4 VTs and 1 VF, all in the ICD group). All HRV parameters were significantly lower in patients with, compared with those without, arrhythmic events. Low-frequency amplitude was the most significant HRV variable associated with arrhythmic events in univariate Cox regression analysis (P=0.017), and was the only significant predictor of arrhythmic events in multivariable regression analysis (hazard ratio 0.88, P=0.047), together with unexplained syncope (hazard ratio 16.1, P=0.039). CONCLUSIONS: Our data show that among ARVC/D patients HRV analysis might be helpful in identifying those with increased risk of major arrhythmic events.

T-wave alternans in apparently healthy subjects and in different subsets of patients with ischaemic heart disease.

AIMS: Microvolt T-wave alternans (TWA) predicts arrhythmic risk in patients with ischaemic heart disease (IHD). While TWA has widely been assessed by the spectral method, it has been poorly characterized in healthy people as well as in IHD patients by the modified moving average (MMA) method. METHODS AND RESULTS: We enrolled 729 consecutive subjects, referred for exercise stress test (EST). T-wave alternans was assessed by the MMA method, considering all 12 electrocardiogram (ECG) leads (TWA_tot) or the 6 ECG pre-cordial leads only (TWA_prec). Patients were divided into five groups: (i) no history of IHD and normal EST (Group 1); (ii) no history of IHD but positive EST (Group 2); (iii) ischaemic heart disease without any acute myocardial infarction [AMI (Group 3)]; (iv) old AMI (Group 4); (v) recent AMI (Group 5). T-wave alternans values >95th percentile of those measured in Group 1 were considered 'abnormal'. The 95th percentile of TWA values in Group 1 was 75 µV for TWA_tot and 65 µV for TWA_prec. T-wave alternans values and prevalence of abnormal TWA increased from Groups 1-2 to Group 5 (P< 0.00001 for both). Group 4 and Group 5, compared with Group 1, showed a significant higher prevalence of abnormal values of TWA_tot [odds ratio (OR) 1.70 (P= 0.002), and 2.07 (P= 0.01), respectively] and TWA_prec [OR 1.51 (P= 0.02) and 2.37 (P= 0.003), respectively] at multivariable analysis. In IHD patients EST-induced ischaemia did not influence TWA; in AMI patients, impaired left ventricular function was associated with higher TWA values. CONCLUSIONS: In healthy people, TWA_tot and TWA_prec were ≤75 and ≤65 µV, respectively, in 95% of subjects. In IHD patients TWA values were higher compared with healthy individuals; a history of AMI was independently associated with abnormal TWA values.

Upper arm intermittent ischaemia reduces exercise-related increase of platelet reactivity in patients with obstructive coronary artery disease.

OBJECTIVE: To assess whether upper arm ischaemia influences exercise-induced myocardial ischaemia and platelet activation in patients with coronary artery disease (CAD). DESIGN: Crossover study. SETTING: University hospital. PATIENTS: Twenty patients (17 men) of mean±SD age 64±8 years with stable CAD. INTERVENTIONS: Patients underwent two exercise stress tests (ESTs) on two separate days in a randomised manner: (1) a maximal EST only (EST-1); (2) a maximal EST after intermittent upper arm ischaemia (cycles of alternating 5-min inflation and 5-min deflation of a standard blood pressure cuff) (EST-2). Blood samples were obtained to evaluate platelet reactivity. MAIN OUTCOME MEASURES: Platelet reactivity was assessed by flow cytometry at rest and after EST, with and without ADP stimulation, by measuring the percentage of monocyte-platelet aggregates (MPAs) and CD41 platelet expression measured as mean fluorescence intensity. RESULTS: Remote ischaemia had no significant effect on EST-induced myocardial ischaemia. At rest there were no differences before EST-1 and EST-2 in basal MPA (20.7±2.3 vs 20.8±2.4, p=0.56) and CD41 (21.5±2.3 vs 21.3±2.3, p=0.39), and ADP stimulation induced a similar increase in both MPA (+15.2±8.2% vs +14.9±8.4%, p=0.71) and CD41 (+15.7±5.7% vs 13.37±6.9%, p=0.59). While no differences in the increase in MPA and CD41 expression were observed after EST-1 and EST-2, ADP stimulation after EST-2 induced a lower increase in MPA (+18.3±8.1% vs +27.9±9.7%, p<0.001) and CD41 (+18.3±9.2% vs +27.2±12.4%, p<0.001) than after EST-1. CONCLUSION: These results show that, in patients with stable CAD, remote ischaemia induces protection against an exercise-related increase in platelet reactivity.

Platelet reactivity and endothelial function in children of patients with early acute myocardial infarction.

AIMS: To assess whether platelet reactivity is increased in offspring of patients with early acute myocardial infarction (AMI) and its possible relation with endothelial dysfunction. METHODS AND RESULTS: We studied 23 healthy children (15±3 years, 13 males) of patients with early AMI (≤50 years old; Group 1) and 21 healthy children of healthy subjects without any history of cardiovascular disease (14±3 years, 10 males; Group 2). Platelet reactivity was assessed by flow cytometry as the increase in monocyte-platelet aggregates (MPA) and CD41 and PAC-1 platelet expression in response to exercise stress test (EST), adenosine diphosphate (ADP) stimulation (10(-7) M), or both. Endothelial function was assessed by measuring brachial artery dilation during post-ischaemic forearm hyperaemia [flow-mediated dilation (FMD)]. Both EST and ADP induced a higher percentage increase in platelet receptor expression in Group 1, compared with Group 2, with the most significant difference being shown for the response to the combined stimuli (e.g. MPA, 23.1±12 vs. 5.63±8%, P<0.001; platelet PAC-1, 57.7±47 vs. 13.2±7%, P<0.001). Compared with Group 2, Group 1 children showed lower FMD (10.7±3.1 vs. 8.0±2.9%, respectively; P=0.007). However, no significant association was found between FMD and platelet reactivity. CONCLUSION: Our results show increased platelet reactivity in children of patients with early AMI; the finding was not significantly correlated with endothelial dysfunction, suggesting that other mechanisms are mainly involved in the enhanced platelet response to agonistic stimuli.

Evidence of increased platelet reactivity in the first six months after acute ST segment elevation myocardial infarction.

INTRODUCTION: Platelets play a crucial role in the pathogenesis of acute coronary syndromes. Accordingly, previous studies showed increased platelet reactivity on admission in these patients. In this study we assessed platelet reactivity at short-medium term follow-up in patients with ST-segment elevation acute myocardial infarction (STEMI). MATERIALS AND METHODS: Fifty-nine patients (58 ± 11 years, 45 men), treated with primary angioplasty, were studied 1 month after STEMI. Thirty-five patients were retested at 6 months. Twenty matched patients with stable coronary artery disease served as controls. Platelet reactivity was assessed by flow cyometry at rest and at peak exercise, with and without adenosine diphosphate (ADP) stimulation, by measuring monocyte-platelet aggregates (MPAs) and glycoprotein IIb/IIIa (CD41) expression in the MPA gate, and CD41 and fibrinogen receptor (PAC-1) expression in the platelet gate. RESULTS: Compared to controls, basal MPAs and CD41 in the MPA gate were higher in STEMI patients both at 1 month (p = 0.001 and p = 0.002, respectively) and at 6 months (p = 0.03 and p = 0.01, respectively). Basal CD41 and PAC-1 expression was also higher in STEMI patients at the two assessments compared to controls (P<0.001 for both). Exercise induced a similar increase in platelet reactivity in patients and controls. ADP induced a higher increase in CD41 platelet expression in STEMI patients compared to controls both at 1 and 6 months (P < 0.001). CONCLUSION: Platelet reactivity is increased in the first 6 months after STEMI. The persistence of increased platelet reactivity in this time period may play a role in the early recurrence of coronary events after STEMI.