Electrocardiographic characteristics of right-bundle-branch-block premature ventricular complexes predicting absence of left ventricular scar in athletes with apparently structural normal heart.

AIMS: Left ventricular scar is an arrhythmic substrate that may be missed by echocardiography and diagnosed only by cardiac magnetic resonance (CMR), which is a time-consuming and expensive imaging modality. Premature ventricular complexes (PVCs) with a right-bundle-branch-block (RBBB) pattern are independent predictors of late gadolinium enhancement (LGE) but their positive predictive value is low. We studied which electrocardiographic features of PVCs with an RBBB pattern are associated with a higher probability of the absence of an underlying LGE. METHODS: The study included 121 athletes (36 ± 16 years; 48.8% men) with monomorphic PVCs with an RBBB configuration and normal standard clinical investigations who underwent CMR. LGE was identified in 35 patients (29%), predominantly in those with PVCs with a superior/intermediate axis (SA-IntA) compared to inferior axis (IA) (38% vs. 10%, P = 0.002). Among patients with SA-IntA morphology, the contemporary presence of qR pattern in lead aVR and V1 was exclusively found in patients without LGE at CMR (51.0% vs. 0%, P < 0.0001). Among patients with IA, the absence of LGE correlated to a narrow ectopic QRS (145 ± 16 vs. 184 ± 27 msec, P < 0.001). CONCLUSIONS: Among athletes with apparently idiopathic PVCs with a RBBB configuration, the presence of a concealed LGE at CMR was documented in 29% of cases, mostly in those with a SA-IntA. In our experience, the contemporary presence of qR pattern in lead aVR and V1 in PVCs with RBBB/SA-IntA morphology or, on the other hand, a relatively narrow QRS in PVCs with an IA, predicted absence of LGE.

The electrocardiogram in non-ischaemic-dilated cardiomyopathy.

This article summarizes the main electrocardiogram (ECG) findings in dilated cardiomyopathy (DCM) patients. Recent reports are described in the great 'pot' of DCM peculiar ECG patterns that are typical of specific forms of DCM. Patients with late gadolinium enhancement on CMR, who are at greatest arrhythmic risk, have also distinctive ECG features. Future studies in large DCM populations should evaluate the diagnostic and prognostic value of the ECG.

Arrhythmic CArdiac DEath in MYotonic dystrophy type 1 patients (ACADEMY 1) study: the predictive role of programmed ventricular stimulation.

AIMS: Myotonic dystrophy type 1 (DM1) predisposes to the development of life-threatening arrhythmias and sudden cardiac death. Our study aimed to evaluate the prognostic value of programmed ventricular stimulation (PVS) in DM1 patients with conduction system disease. METHODS AND RESULTS: Arrhythmic CArdiac DEath in MYotonic dystrophy type 1 patients (ACADEMY 1) is a double-arm non-randomized interventional prospective study. Myotonic dystrophy type 1 patients with permanent cardiac pacing indication were eligible for the inclusion. The study population underwent to pacemaker (PM) or implantable cardioverter-defibrillator (ICD) implantation according to the inducibility of ventricular tachyarrhythmias at PVS. Primary endpoint of the study was a composite of appropriate ICD therapy and cardiac arrhythmic death. The secondary study endpoint was all-cause mortality. Seventy-two adult-onset DM1 patients (51 ± 12 years; 39 male) were enrolled in the study. A ventricular tachyarrhythmia was induced in 25 patients (34.7%) at PVS (PVS+) who underwent dual chambers ICD implantation. The remaining 47 patients (65.3%) without inducible ventricular tachyarrhythmia (PVS-) were treated with dual-chamber PM. During an average observation period of 44.7 ± 10.2 months, nine patients (12.5%) met the primary endpoint, four in the ICD group (16%) and five (10.6%) in the PM group. Thirteen patients died (18.5%), 2 in the ICD group (8%) and 11 in PM group (23.4%). The Kaplan-Meier analysis did not show a significantly different risk of both primary and secondary endpoint event rates between the two groups. CONCLUSIONS: The inducibility of ventricular tachyarrhythmias has shown a limited value in the arrhythmic risk stratification among DM1 patients.

Clinical Spectrum and Outcome of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome and No Obstructive Coronary Atherosclerosis.

BACKGROUND: Because approximately 10% of patients with no-ST-segment elevation acute coronary syndrome (NSTE-ACS) show no obstructive coronary artery disease (NOCAD) on angiography, we assessed the spectrum of diagnoses and the predictors of outcome of these patients. METHODS AND RESULTS: We studied 178 patients admitted to a coronary care unit with an initial diagnosis of NSTE-ACS, based on clinical, ECG and laboratory data, but found to have NOCAD. The final diagnosis in these patients was heterogeneous; true NSTE-ACS (ie, coronary thrombosis on an unstable plaque) was ascertained in 1 patient (0.6%), whereas diagnosis at discharge was microvascular NSTE-ACS in 56.2% of patients, variant angina in 10.1%, myocarditis in 8.9%, takotsubo disease in 7.9%, tachyarrhythmia-related chest pain in 6.7%, and non-cardiac pain in 9.6%. At 24.5-month follow-up, 21 deaths (11.8%) had occurred, 9 (5.1%) from cardiovascular causes, including 2 (1.12%) coronary deaths. By multivariable Cox analysis, age only predicted global (hazard ratio [HR] 1.07 [1.02-1.12]; P=0.006) and cardiovascular (HR 1.08 [1.01-1.16]; P=0.04) mortality; non-coronary vascular disease was the main predictor of cardiovascular death or readmission for cardiovascular disease (HR 3.28 [1.75-6.14]; P<0.001) and coronary death or readmission for angina (HR 3.20 [1.26-8.14]; P=0.014). CONCLUSIONS: Patients with an initial diagnosis of NSTE-ACS constitute a heterogeneous population with different final diagnoses. Patients have a rather high rate of fatal events, most of which, however, are not related to coronary causes. (Circ J 2016; 80: 1600-1606).

Effect of remote ischemic preconditioning on platelet activation and reactivity induced by ablation for atrial fibrillation.

BACKGROUND: Radiofrequency ablation of atrial fibrillation has been associated with some risk of thromboembolic events. Previous studies showed that preventive short episodes of forearm ischemia (remote ischemic preconditioning [IPC]) reduce exercise-induced platelet reactivity. In this study, we assessed whether remote IPC has any effect on platelet activation induced by radiofrequency ablation of atrial fibrillation. METHODS AND RESULTS: We randomized 19 patients (age, 54.7±11 years; 17 male) undergoing radiofrequency catheter ablation of paroxysmal atrial fibrillation to receive remote IPC or sham intermittent forearm ischemia (control subjects) before the procedure. Blood venous samples were collected before and after remote IPC/sham ischemia, at the end of the ablation procedure, and 24 hours later. Platelet activation and reactivity were assessed by flow cytometry by measuring monocyte-platelet aggregate formation, platelet CD41 in the monocyte-platelet aggregate gate, and platelet CD41 and CD62 in the platelet gate in the absence and presence of ADP stimulation. At baseline, there were no differences between groups in platelet variables. Radiofrequency ablation induced platelet activation in both groups, which persisted after 24 hours. However, compared with control subjects, remote IPC patients showed a lower increase in all platelet variables, including monocyte-platelet aggregate formation (P<0.0001), CD41 in the monocyte-platelet aggregate gate (P=0.002), and CD41 (P<0.0001) and CD62 (P=0.002) in the platelet gate. Compared with control subjects, remote IPC was also associated with a significantly lower ADP-induced increase in all platelet markers. CONCLUSIONS: Our data show that remote IPC before radiofrequency catheter ablation for paroxysmal atrial fibrillation significantly reduces the increased platelet activation and reactivity associated with the procedure.

Determinants of heart rate turbulence in individuals without apparent heart disease and in patients with stable coronary artery disease.

AIMS: To assess the characteristics and determinants of heart rate turbulence (HRT) in individuals without any apparent heart disease and in patients with coronary artery disease (CAD). METHODS AND RESULTS: Heart rate turbulence parameters, turbulence onset (TO), and turbulence slope (TS) were calculated on 24 h electrocardiogram recordings in 209 individuals without any heart disease (group 1) and in 157 CAD patients (group 2). In group 1, only age independently predicted abnormal TO (≥0%) [odds ratio (OR), 1.05; P<0.001], while predictors of abnormal TS (≤2.5 ms/RR) were age (OR, 0.85; P < 0.001) and hypertension (OR, 0.19; P = 0.028). In group 2 patients, only age independently predicted TO (OR, 1.03; P = 0.038), while age (OR, 0.90; P = 0.001) and left ventricular ejection fraction (LVEF; OR, 1.07; P = 0.008) predicted TS. Heart rate turbulence values were different in groups 1 and 2. Turbulence onset was (mean, standard deviation) -1.80 ± 2.24 vs. -0.73 ± 1.61%, respectively (P < 0.001), whereas TS was (median, interquartile interval) 5.83 (3.25-10.55) vs. 2.93 (1.73-5.81) ms/RR, respectively (P < 0.001). Coronary artery disease group, however, did not predict abnormal HRT parameters in multivariable analyses, both in the whole population and when comparing two subgroups matched for age and gender. Age and (for TS) LVEF, indeed, were the only independent predictors of abnormal HRT. CONCLUSIONS: Age is a major HRT determinant both in subjects without any apparent heart disease and in stable CAD patients. Hypertension and LVEF contribute independently to HRT in these two groups, respectively. Coronary artery disease group was not by itself associated with abnormal HRT parameters in multivariable analyses.

Poor tolerance and limited effects of isosorbide-5-mononitrate in microvascular angina.

OBJECTIVES: To assess the effects of isosorbide-5-mononitrate (ISMN) in patients with microvascular angina (MVA). METHODS: We randomized 20 MVA patients, treated with a ß-blocker or a calcium antagonist, to 60 mg slow-release ISMN (halved to 30 mg if not tolerated) or placebo once a day for 4 weeks; the patients were then switched to the other treatment for another 4 weeks. Their clinical status was assessed with the Seattle Angina Questionnaire (SAQ) and the EuroQoL score for quality of life. The exercise stress test (EST), coronary blood flow (CBF) response to nitrate and the cold pressor test (CPT), brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) were also assessed. RESULTS: Nine patients (45%) did not complete the ISMN phase due to side effects; 2 patients refused a follow-up. Nine patients completed the study. The SAQ and EuroQoL scores were significantly better with ISMN than with placebo, although the differences were small. No differences were found between the treatments in the EST results, CBF response to nitroglycerin (p = 0.55) and the CPT (p = 0.54), FMD (p = 0.26) and NMD (p = 0.35). CONCLUSIONS: In this study, a high proportion of MVA patients showed an intolerance to ISMN; in those tolerating the drug, significant effects on their angina status were observed, but the benefit appeared to be modest and independent of effects on coronary microvascular function.

Peripheral arterial function and coronary microvascular function in patients with variant angina.

OBJECTIVES: In this study, we assessed whether any abnormalities in coronary microvascular and peripheral vasodilator functions are present in patients with variant angina (VA) caused by epicardial coronary artery spasm (CAS). METHODS: We studied 23 patients with VA (i.e. angina at rest, ST-segment elevation during angina attacks and documented occlusive CAS at angiography) and 18 matched healthy controls. Endothelium-dependent and -independent coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to adenosine and the cold pressor test (CPT) in the left anterior descending artery by transthoracic Doppler echocardiography. Systemic endothelium-dependent and -independent arterial dilator function was assessed by measuring brachial flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), respectively. RESULTS: In VA patients, CBF responses to both adenosine (1.71 ± 0.25 vs. 2.97 ± 0.80, p < 0.01) and CPT (1.68 ± 0.23 vs. 2.58 ± 0.60, p < 0.01) were reduced compared to controls. Brachial FMD was also lower (3.87 ± 2.06 vs. 8.51 ± 2.95%, p < 0.01), but NMD was higher (16.7 ± 1.8 vs. 11.9 ± 1.4%, p < 0.01) in patients compared to controls. Differences were independent of the presence of coronary atherosclerotic lesions at angiography. CONCLUSIONS: Our data show that patients with VA have a generalized vascular dysfunction that involves both peripheral artery vessels and coronary microcirculation.

A novel electrocardiographic predictor of clinical response to cardiac resynchronization therapy.

AIMS: A wide QRS with left bundle branch block pattern is usually required for cardiac resynchronization therapy (CRT) in patients with dilated cardiomyopathy. However, ∼30% of patients do not benefit from CRT. We evaluated whether a detailed analysis of QRS complex can improve prediction of CRT success. METHODS AND RESULTS: We studied 51 patients (67.3 + 9.5 years, 36 males) with classical indication to CRT. Twelve-lead electrocardiogram (ECG) (50 mm/s, 0.05 mV/mm) was obtained before and 3 months after CRT. The following ECG intervals were measured in leads V1 and V6: (i) total QRS duration; (ii) QRS onset-R wave peak; (iii) R wave peak-S wave peak (RS-V1 and RS-V6); (iv) S wave peak-QRS end; and (v) difference between QR in V6 and in V1. Patients were considered as responder when left ventricular ejection fraction (LVEF) increased by ≥5% and New York Heart Association class by ≥1 after 3 months of CRT. Of ECG intervals, only basal RS-V1 was longer in responders (n = 36) compared with non-responders (52.9 ± 11.8 vs. 44.0 ± 12.6 ms, P = 0.021). Among patients with RS-V1 ≥45 ms 83% responded to CRT vs. 33% of those with RS-V1 < 45 ms (P < 0.001). RS-V1 ≥ 45 ms was independently associated with response to CRT in multivariable analysis (odds ratio 9.8; P = 0.002). A reduction of RS-V1 ≥ 10 ms by CRT also significantly predicted clinical response. RS-V1 shortening correlated with improvement in LVEF (r = -0.45; P < 0.001) and in MS (r = 0.46; P < 0.001). CONCLUSION: Our data point out that RS-V1 interval and its changes with CRT may help to identify patients who are most likely to benefit from CRT.

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.

Lack of effect of nitrates on exercise stress test results in patients with microvascular angina.

PURPOSE: To assess the effects of short-acting nitrates on exercise stress test (EST) results and the relation between EST results and coronary blood flow (CBF) response to nitrates in patients with microvascular angina (MVA). METHODS: We completed 2 symptom/sign limited ESTs on 2 separate days, in a random sequence and in pharmacological washout, in 29 MVA patients and in 24 patients with obstructive coronary artery disease (CAD): one EST was performed without any intervention (control EST, C-EST), and the other after sublingual isosorbide dinitrate, 5 mg (nitrate EST, N-EST). CBF response to nitroglycerin (25 µg) was assessed in the left anterior descending coronary artery by transthoracic Doppler-echocardiography. RESULTS: At C-EST. ST-segment depression ≥1 mm (STD) was induced in 26 (90 %) and 23 (96 %) MVA and CAD patients, respectively (p=0.42), whereas at N-EST, STD was induced in 25 (86 %) and 14 (56 %) MVA and CAD patients, respectively (p=0.01). Time and rate pressure product at 1 mm STD increased during N-EST, compared to C-EST, in CAD patients (475±115 vs. 365±146 s, p<0.001; and 23511±4352 vs. 20583±6234 bpm∙mmHg, respectively, p=0.01), but not in MVA patients (308±160 vs. 284±136 s; p=0.19; and 21290±5438 vs. 20818±4286 bpm∙mmHg, respectively, p=0.35). In MVA patients, a significant correlation was found between heart rate at STD during N-EST and CBF response to nitroglycerin (r=0.40, p=0.04). CONCLUSIONS: Short-acting nitrates improve EST results in CAD, but not in MVA patients. In MVA patients a lower nitrate-dependent coronary microvascular dilation may contribute to the lack of effects of nitrates on EST results.

The Diagnostic Value of the 12-Lead ECG in Arrhythmogenic Left Ventricular Cardiomyopathy: Novel ECG Signs.

BACKGROUND: Electrocardiographic (ECG) findings in arrhythmogenic left ventricular cardiomyopathy (ALVC) are limited to small case series. OBJECTIVES: This study aimed to analyze the ECG characteristics of ALVC patients and to correlate ECG with cardiac magnetic resonance and genotype data. METHODS: We reviewed data of 54 consecutive ALVC patients (32 men, age 39 ± 15 years) and compared them with 84 healthy controls with normal cardiac magnetic resonance. RESULTS: T-wave inversion was often noted (57.4%), particularly in the inferior and lateral leads. Low QRS voltages in limb leads were observed in 22.2% of patients. The following novel ECG findings were identified: left posterior fascicular block (LPFB) (20.4%), pathological Q waves (33.3%), and a prominent R-wave in V1 with a R/S ratio ≥0.5 (24.1%). The QRS voltages were lower in ALVC compared with controls, particularly in lead I and II. At receiver-operating characteristic analysis, the sum of the R-wave in I to II ≤8 mm (AUC: 0.909; P < 0.0001) and S-wave in V1 plus R-wave in V6 ≤12 mm (AUC: 0.784; P < 0.0001) effectively discriminated ALVC patients from controls. It is noteworthy that 4 of the 8 patients with an apparently normal ECG were recognized by these new signs. Transmural late gadolinium enhancement was associated to LPFB, a R/S ratio ≥0.5 in V1, and inferolateral T-wave inversion, and a ringlike pattern correlated to fragmented QRS, SV1+RV6 ≤12 mm, low QRS voltage, and desmoplakin alterations. CONCLUSIONS: Pathological Q waves, LPFB, and a prominent R-wave in V1 were common ECG signs in ALVC. An R-wave sum in I to II ≤8 mm and SV1+RV6 ≤12 mm were specific findings for ALVC phenotypes compared with controls.

Ventricular arrhythmias and risk stratification of cardiac sudden death in athletes.

Sudden cardiac death (SCD) of young athletes is an unexpected and tragic event that could occur during sport activities and is frequently related to ventricular arrhythmias. Identifying athletes at risk of SCD remains a major challenge. While specific characteristics of premature ventricular contractions are considered common and benign, other "uncommon" features should require more accurate investigations, in order to determine eligibility for competitive sports. The most common type of idiopathic premature ventricular contractions originates from ventricular outflow tract and is characterized by an ECG pattern with left bundle branch block and inferior QRS axis (infundibular pattern). Another pattern associated with a good prognosis is the "fascicular" morphology, characterized by a typical right bundle branch block, superior QRS axis morphology and QRS duration <130 ms. Conversely, other morphological features (such as left bundle branch block /intermediate or superior axis or right bundle branch block/intermediate or superior axis and wide QRS) correlate to an underlying substrate. In risk stratification setting, cardiac magnetic resonance plays a key role allowing an accurate identification of myocardial tissue abnormalities, which could affect athletes' prognosis. This review focuses on characteristics of premature ventricular contractions characteristics in terms of morphology, distribution, complexity and response to exercise and describes the possible underlying myocardial substrates. This review also critically analyzes the evaluation process of athletes with premature ventricular contractions necessary for an accurate risk stratification.

Effect of Remote Ischemic Preconditioning on Platelet Activation Induced by Coronary Procedures.

In this study, we aim to assess whether remote ischemic preconditioning (RIPC) reduces platelet activation during coronary angiography (CA) and/or percutaneous coronary interventions. We studied 30 patients who underwent CA because of a suspect of stable angina. Patients were randomized to RIPC (3 short episodes of forearm ischemia) or sham RIPC (controls) before the procedure. Blood samples were collected at baseline, at the end of the procedure, and 24 hours later. Monocyte-platelet aggregate (MPA) formation and platelet CD41 in the MPA gate and CD41 and CD62 expression in the platelet gate were assessed by flow cytometry, in the absence and in the presence of adenosine diphosphate (ADP) stimulation. A significant increase in platelet activation occurred during the invasive procedure in controls, which persisted at 24 hours. However, compared with controls, RIPC group showed no or a lower increase in platelet variables, including MPA formation (p <0.0001) and CD41 (p = 0.002) in the MPA gate and CD41 (p <0.0001) and CD62 (p = 0.002) in the platelet gate. ADP increased platelet activation at baseline, but did not further increase platelet reactivity during the invasive procedure in either groups. Percutaneous coronary interventions, performed in 10 patients (6 in the RIPC group and 4 in controls), did not have any further significant effect on platelet activation and reactivity compared with CA alone. In conclusion, RIPC reduces platelet activation occurring during CA. In contrast, no effects were observed on platelet response to ADP stimulation, probably related to the administration of an ADP antagonist in all patients.

Use of T-wave alternans in identifying patients with coronary artery disease.

AIMS: Microvolt T-wave alternans (MTWA) has been found to predict fatal events in patients with coronary artery disease (CAD). In a previous study, we found that MTWA values are higher in patients with CAD, compared with apparently healthy individuals. In this study, we assessed the relation between CAD and MTWA in patients with a diagnosis based on coronary angiography results. METHODS: We studied 98 consecutive patients undergoing coronary angiography for suspected CAD. All patients underwent a maximal exercise stress test (EST), and MTWA was measured in the precordial ECG leads. Patients were divided into three groups: 40 patients without any significant (>50%) stenosis (group 1); 47 patients with significant stenosis (group 2); and 11 patients with a previous percutaneous coronary intervention (PCI) who had no evidence of restenosis (group 3). EST was repeated after 1 month in 24 group 2 patients who underwent PCI and in 17 group 1 patients. RESULTS: MTWA was significantly higher in group 2 (58.7 ±â€Š24 µV) compared with group 1 (34.2  ±â€Š15 µV, P < 0.01) and group 3 (43.2 ±â€Š24 µV, P < 0.05). An MTWA greater than 60 µV had 95% specificity and 82% positive predictive value for obstructive CAD. At 1-month follow-up, MTWA decreased significantly in patients treated with PCI (from 61.3 ±â€Š22 to 43.5 ±â€Š17 µV; P < 0.001), but not in group 1 patients (from 50.5 ± 22 to 44.3 ±â€Š19 µV, P = 0.19). CONCLUSION: MTWA is increased in patients with obstructive CAD and is reduced by coronary revascularization. An assessment of MTWA can be helpful in identifying which patients with suspected CAD are likely to show obstructive CAD on angiography.

Persistent enhanced platelet activation in patients with acute myocardial infarction and coronary microvascular obstruction: clinical implications.

About 30% of patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing recanalisation of the infarct-related coronary artery do not achieve valid myocardial reperfusion (no-reflow phenomenon or coronary microvascular obstruction [MVO]). The mechanisms of MVO are incompletely understood. In this study we investigated the role platelet activation in the pathogenesis of coronary MVO in STEMI patients. We enrolled 48 STEMI patients (age 56.2 ± 11 years; 31 men), treated by primary percutaneous coronary intervention (PCI) followed by double anti-platelet treatment, and 20 control patients with stable coronary artery disease (CAD) on single anti-platelet treatment (age 57.5 ± 6 years, 12 men). STEMI patients were divided into two groups: 35 patients with complete myocardial reperfusion (MR) and 13 patients with coronary MVO despite successful PCI. Platelet activation was assessed on admission and at one-month follow-up by measuring platelet receptor expression and monocyte-platelet aggregates (MPAs). Platelet receptor expression, platelet receptor conformational change for fibrinogen binding availability and MPA formation were increased in STEMI patients with MVO compared to both STEMI patients with MR and stable CAD patients, both on admission and at one-month follow-up (p<0.05 for all).Among STEMI patients, platelet activation is greater in those who display coronary MVO, compared to those with MR, after successful PCI, both on admission and one month after STEMI, suggesting that enhanced platelet activation might be involved in the pathogenesis of MVO. The persistence of enhanced platelet activation despite double classical anti-platelet therapy suggests that new anti-platelet strategies should be considered in patients with coronary MVO.

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.

Clinical correlates and prognostic value of flow mediated dilation in patients with non-ST segment elevation acute coronary syndromes.

Endothelial dysfunction can predict cardiovascular outcomes in several populations of patients. The aim of this study was to assess the severity, time course, and clinical implications of endothelial dysfunction in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). Sixty patients with NSTE ACS (mean age 62 ± 8 years, 44 men) and 40 controls with stable coronary artery disease (CAD) (mean age 63 ± 10 years, 27 men) were studied. In patients with NSTE ACS and in those with stable CAD, endothelial function was assessed <12 hours after admission and at 3-month follow-up by measuring right brachial artery dilation after 5 minutes of forearm ischemia (flow-mediated dilation [FMD]). Clinical outcomes were assessed after a median follow-up period of 32 months (range 14 to 36). The primary end point was a combination of cardiac death or readmission for new ACS or recurrence of angina pectoris. FMD on admission was significantly lower in patients with NSTE ACS compared to those with stable CAD (2.1 ± 1.2% vs 4.8 ± 1.9%, p <0.001). FMD improved significantly at 3-month follow-up in patients with NSTE ACS, becoming comparable to that in patients with stable CAD (5.7 ± 2.6% vs 5.5 ± 1.7%, p = 0.93). During follow-up, 14 cardiac events (23%) occurred in patients with NSTE ACS. On multivariate analysis, only diabetes (hazard ratio 18.1, 95% confidence interval 3.9 to 83.9, p <0.001) and FMD at 3 months (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, p = 0.04) were independent predictors of the primary end point in patients with NSTE ACS. In conclusion, endothelial function is markedly impaired in the acute phase of NSTE ACS but improves significantly at 3-month follow-up. In patients with NSTE ACS, FMD at 3 months after the acute event is a significant independent predictor of cardiac outcomes.

Effect of ranolazine on arterial endothelial function in patients with type 2 diabetes mellitus.

OBJECTIVE: To assess the effect of ranolazine on systemic vascular function in patients with type II diabetes mellitus (T2DM). METHODS: We randomized 30 consecutive T2DM patients with no evidence of cardiovascular disease and no insulin therapy to receive one of the following 3 forms of treatment in a blinded fashion: ranolazine, 375 mg bid for 3 weeks (group 1); ranolazine, 375 mg bid for 2 weeks, followed by placebo bid for 1 week (group 2); placebo bid for 3 weeks (group 3). Flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the right brachial artery were assessed at baseline and after 48 h, and 2 and 3 weeks. RESULTS: FMD and NMD were similar among groups at baseline. Compared to the basal value, FMD significantly improved after 2 weeks in group 1 and in group 2 (p < 0.01 for both), but not in group 3. At 3 weeks, FMD remained improved, compared to baseline, in group 1 (p < 0.05), whereas returned to basal values in group 2 (p = 0.89 vs. baseline). No changes in NMD were observed in any group. CONCLUSIONS: In this controlled study, ranolazine was able to improve endothelial function in T2DM patients.

Differential effects of heart rate reduction by atenolol or ivabradine on peripheral endothelial function in type 2 diabetic patients.

OBJECTIVE: To assess whether reduction of heart rate (HR) has beneficial effects on endothelial function in patients with type 2 diabetes mellitus (T2DM). DESIGN: Randomised, double-blind, placebo-controlled study. SETTING: University hospital. PATIENTS: 66 T2DM patients without overt cardiovascular disease. INTERVENTIONS: Patients were randomised to receive for 4 weeks, in addition to their standard therapy, one of the following treatments: atenolol (25 mg twice daily), ivabradine (5 mg twice daily) or placebo (1 tablet twice daily). MAIN OUTCOME MEASURES: Systemic endothelial function, assessed by flow-mediated dilation (FMD); endothelium-independent vasodilation, assessed by nitrate-mediated dilation (NMD); cardiac autonomic function, assessed by HR variability (HRV). RESULTS: 61 patients completed the study (19, 22 and 20 patients in atenolol, ivabradine and placebo groups, respectively). Compared with baseline, HR was similarly reduced by atenolol (87±13 vs 69±9 bpm) and ivabradine (86±12 to 71±9 bpm), but not by placebo (82±10 vs 81±9 bpm) (p<0.001). FMD improved at follow-up in the atenolol group (4.8±1.7 vs 6.4±1.9%), but not in the ivabradine group (5.2±2.5 vs 4.9±2.2%) and in the placebo group (4.8±1.5 vs 4.7±1.7%) (p<0.01). NMD did not change significantly in any group. HRV parameters did not change in the placebo group; they, instead, consistently increased in the atenolol, whereas a mild increase in SDNNi was only observed in the ivabradine group. A significant correlation was found in the atenolol group between HR and FMD changes (r=-0.48; p=0.04). CONCLUSIONS: Despite a comparable reduction in HR, atenolol, but not ivabradine, improved FMD in T2DM patients suggesting that changes in HR are by themselves unlikely to significantly improve endothelial function.