Roberto Mollo

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

Abstract.  Lanza GA, Barone L, Scalone G, Pitocco D, Sgueglia GA, Mollo R, Nerla R, Zaccardi F, Ghirlanda G, Crea F (Istituto di Cardiologia; and Università Cattolica del Sacro Cuore, Roma; Italy). Inflammation‐related effects of adjuvant influenza A vaccination on platelet activation and cardiac autonomic function. J Intern Med 2010; 269: 118–125.

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.

Prevalence and clinical correlates of early repolarization and J wave in a large cohort of subjects without overt heart disease

BACKGROUND Recent studies have suggested that early repolarization (ER) is associated with increased risk of ventricular tachyarrhythmias. Early repolarization in these studies, however, was defined as J-wave (terminal QRS slurring or notching) or J-point elevation rather than typical ST-segment elevation (STE). Prevalence and characteristics of these different findings in the general population are poorly known. In this study, we assessed prevalence and correlates of STE typical of ER and of J wave in a large population of noncardiac subjects. METHODS We prospectively collected electrocardiograms of 4176 consecutive subjects without heart disease at our hospital. RESULTS Early repolarization was found in 84 subjects (2.0%) and J wave in 663 (15.9%). Among ER subjects, a J wave was present in 60 (71.4%). Variables independently associated with both ER and J wave included young age, male sex, and lower heart rate. There was no increased history of symptoms (palpitations and syncope) possibly related to arrhythmias in STE or J-wave subjects. CONCLUSIONS Typical ER pattern and J wave are common in noncardiac subjects, particularly in young people, and are not associated with symptoms potentially related to arrhythmias.

Cardiac adrenergic nerve function in patients with cardiac syndrome X.

Background We previously found a severe impairment of cardiac uptake of 123I-metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, on myocardial scintigraphy in a small group of patients with cardiac syndrome X (CSX), suggesting a dysfunction of cardiac adrenergic nerve fibres. In this study, we assessed the consistency of these previous findings in a larger group of these patients. Methods Planar and single-photon emission computed tomography MIBG myocardial scintigraphy was performed in 40 CSX patients (58 ± 7 years, 17 men). Cardiac MIBG uptake was measured by the heart/mediastinum ratio and by a single-photon emission computed tomography regional cardiac MIBG uptake defect score (higher values = lower uptake). As a control group, we studied 20 healthy individuals (56 ± 6 years, nine men). An exercise stress 99mTc-SestaMIBI myocardial scintigraphy was performed in 34 CSX patients (85%). Results Cardiac MIBG defects were observed in 30 patients (75%), with nine (22.5%) showing no cardiac MIBG uptake at all. Compared with controls, CSX patients showed a significantly lower heart/mediastinum ratio (1.70 ± 0.35 vs. 2.1 ± 0.22, P < 0.001) and a higher cardiac MIBG defect score (27 ± 25 vs. 4.4 ± 2.5, P < 0.001). No differences were found in lung MIBG uptake between the two groups. Reversible perfusion defects on stress myocardial scintigraphy were found in 17 out of 34 CSX patients (50%), all of whom also had abnormal cardiac MIBG uptake; cardiac MIBG uptake abnormalities were also present in nine of 17 patients with normal perfusion scintigraphic images. Cardiac MIBG uptake findings were similar in our first 12 patients and in the 28 patients studied subsequently. Conclusion Our data show a relevant impairment of cardiac MIBG uptake in patients with CSX, suggesting that functional abnormalities in cardiac adrenergic nerve function may play a significant role in the mechanisms responsible for the syndrome.

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.

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.

Effect of α-Lipoic Acid on Platelet Reactivity in Type 1 Diabetic Patients

OBJECTIVE Type 1 diabetes is associated with increased platelet reactivity. We investigated whether α-lipoic acid (ALA) has any effect on platelet reactivity in these patients. RESEARCH DESIGN AND METHODS We randomly assigned 51 type 1 diabetic patients to ALA (600 mg once daily) or placebo for 5 weeks. Platelet reactivity was evaluated by the PFA-100 method and by measuring CD41 and CD62 platelet expression. C-reactive protein (CRP) and 8-iso-prostaglandin F2α serum levels also were measured. RESULTS Baseline variables were similar in the two groups. After treatment, closure time was longer (P = 0.006) and CD62P platelet expression was lower, both before (P = 0.002) and after (P = 0.009) ADP stimulation in the ALA group compared with the placebo group. CRP and 8-iso-prostaglandin F2α levels showed no differences between the two groups. CONCLUSIONS Our data show that ALA reduces measures of platelet reactivity ex vivo in type 1 diabetic patients, independently of antioxidant or anti-inflammatory effects.

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 ± 24 &mgr;V) compared with group 1 (34.2 ± 15 &mgr;V, P < 0.01) and group 3 (43.2 ± 24 &mgr;V, P < 0.05). An MTWA greater than 60 &mgr;V 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 ± 22 to 43.5 ± 17 &mgr;V; P < 0.001), but not in group 1 patients (from 50.5 ± 22 to 44.3 ± 19 &mgr;V, 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.

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.

Letter by Montone et al Regarding Article, “Atrial Fibrillation: Outpatient Presentation and Management”

To the Editor: We read with interest the article by Ezekowitz and colleagues1 about outpatient presentation and management of atrial fibrillation (AF). They reported an interesting case of a man presenting for a first diagnosed episode of AF with an unclearly established time of onset. The patient complained of mild fatigue without additional symptoms and was hemodynamically stable. He had a previous history of coronary artery disease treated 4 months earlier with a drug-eluting stent and had been …