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Objective To investigate resting‐state functional connectivity (FC) in pediatric patients with tuberous sclerosis complex and intractable epilepsy requiring surgery. Methods Resting‐state functional MRI was utilized to investigate functional connectivity in 13 pediatric patients with tuberous sclerosis complex (TSC) and intractable epilepsy requiring surgery. Results The majority of patients demonstrated a resting‐state network architecture similar to those reported in healthy individuals. However, preoperative differences were evident between patients with high versus low tuber burden, as well as those with good versus poor neurodevelopmental outcomes, most notably in the cingulo‐opercular and visual resting‐state networks. One patient with high tuber burden and poor preoperative development and seizure control had nearly normal development and seizure resolution after surgery. This was accompanied by significant improvement in resting‐state network architecture just one day postoperatively. Significance Although many patients with tuberous sclerosis complex and medically refractory epilepsy demonstrate functional connectivity patterns similar to healthy children, relationships within and between RSNs demonstrate clear differences in patients with higher tuber burden and worse outcomes. Improvements in resting‐state network organization postoperatively may be related to epilepsy surgery outcomes, providing candidate biomarkers for clinical management in this high‐risk population.

BACKGROUND: Several noninvasive risk factors (NIRFs) have been proposed for sudden cardiac death risk stratification in post‐myocardial infarction (post‐MI) patients with preserved ejection fraction (EF). However, it remains unclear if these factors change over time. METHODS: We evaluated seven electrocardiographic NIRFs as they were described in the PRESERVE‐EF trial in 80 post‐MI patients with EF ≥ 40%, at least 40 days after revascularization and 1 year later. RESULTS: Mean patient age was 56 ± 10 years, and 88% were men. Mean EF was 50 ± 5%. The prevalence of (a) positive late potentials (27.5% vs. 28.8%, p = .860), (b) >30 premature ventricular complexes/hour (8.8% vs. 11.3%, p = .598), (c) nonsustained ventricular tachycardia (8.8% vs. 5%, p = .349), (d) standard deviation of normal RR intervals 440 ms (men) or >450 ms (women) (17.5% vs. 17.5%, p = 1.000), (f) deceleration capacity ≤4.5 ms and heart rate turbulence onset ≥0% and slope ≤2.5 ms (2.5% vs. 3.8%. p = 1.000), and (g) ambulatory T‐wave alternans ≥65 μV in two Holter channels (6.3% vs. 6.3%, p = 1.000) were similar between the two measurements. However, five patients (6.3%) without any NIRFs during the first assessment had at least one positive NIRF at the second assessment and six patients (7.5%) with at least one NIRF at baseline had no positive NIRFs at 1 year. CONCLUSIONS: While the prevalence of the examined electrocardiographic NIRFs between the two examinations was similar on a population basis, some patients without NIRFs at baseline developed NIRFs at 1 year and vice versa, highlighting the need for risk factor reassessment during follow‐up.

Objective The present study investigated whether the glycoprotein (GP)IIb/IIIa receptor blocker abciximab might be a successful bridging strategy to achieve adequate levels of platelet inhibition rapidly in cases where prasugrel is used in morphine-pretreated ST-elevation myocardial infarction (STEMI) patients. Methods In a prospective observational cohort study, 32 patients presenting with STEMI were given prasugrel at a loading dose of 60 mg. Patients were stratified into four groups, according to morphine and/or abciximab use. Adenosine diphosphate (ADP)-induced platelet aggregation was measured at four time points: at baseline, and at 2 h, 1 day and 2 days after prasugrel loading. Results Morphine use was associated with a three-fold higher level of ADP-induced platelet aggregation 2 h after prasugrel loading compared with no morphine/no abciximab (P = 0.019). However, when abciximab was infused in the catheterization laboratory, the effect of morphine on ADP-induced platelet aggregation disappeared (P = 0.884). This interaction was also seen in the presence of high on-treatment platelet reactivity (HTPR) at 2 h; while HTPR was seen in 88% of morphine users/no abciximab users, it was found in only 17–20% in the three other groups (P = 0.003). The effect of morphine disappeared by day 1 – 2. Conclusion The infusion of the GPIIb/IIIa receptor blocker abciximab allows immediate and efficient platelet inhibition in STEMI patients concomitantly receiving the oral ADP receptor blocker prasugrel and morphine.

Objective This study was undertaken to evaluate the influence of preterm birth and other factors on cerebral cortical maturation. Methods We have evaluated the effects of preterm birth on cortical folding by applying cortical cartography methods to a cohort of 52 preterm infants (

Allometry has been used to demonstrate a power-law scaling relationship in the brain of premature born infants. Forty-nine preterm infants underwent neonatal MRI scans and neurodevelopmental testing at age 2. Measures of cortical surface area and total cerebral volume demonstrated a power-law scaling relationship (α = 1.27). No associations were identified between these measures and investigated clinical variables. Term equivalent cortical surface area and total cerebral volume measures and scaling exponents were not related to outcome. These findings confirm a previously reported allometric scaling relationship in the preterm brain, and suggest that scaling is not a sensitive indicator of aberrant cortical maturation.

Objective To test the hypothesis that angiotensin converting enzyme inhibitors (ACEi) affect soluble tumor-necrosis-factor-related apoptosis-inducing ligand (sTRAIL) and this interaction is associated with less in-drug-eluting-stent (DES) neointimal hyperplasia following percutaneous coronary intervention (PCI). Methods From our database of patients with elective PCI and baseline intravascular ultrasound (IVUS) evaluation of the implanted DES, we randomly selected 60 patients who were prescribed an ACEi and 60 matched controls, who did not receive an ACEi following PCI. All patients underwent coronary angiography and IVUS. sTRAIL was measured in samples from the stented coronary artery and a peripheral vein. Results sTRAIL concentration was higher in the ACEi group, both in coronary and peripheral samples: 104 [78–139] pg/ml versus 63 [45–100] pg/ml (P

Summary Aims Little is known about the use of bivalirudin in “real life”. In the context of contemporary antiplatelet treatment, we aimed to assess bivalirudin treatment patterns and short-term (one-month) outcome. Methods Greek Antiplatelet Registry (GRAPE) is a prospective, observational, multicenter cohort study of consecutive, moderate-to-high-risk acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI). We assessed bivalirudin treatment patterns and predictive factors for its use. Combined in-hospital and one-month major adverse cardiovascular events (MACE, including death, myocardial infarction, urgent revascularization, and stroke), and bleeding events according to Bleeding Academic Research Consortium (BARC) criteria were analyzed after propensity matching. Results Of 2047 registered patients, 480 (23.4%) were treated with bivalirudin. Multivariate analysis (C statistic 0.77, 0.75–0.80 95% CIs, P

The authors investigated whether erectile dysfunction (ED) in the early stages of hypertension is associated with heightened end‐organ damage. A total of 174 consecutive men with untreated, newly diagnosed essential hypertension (aged 50.3 years, office blood pressure [BP] 150/98 mm Hg) were studied. All participants underwent 24‐hour ambulatory BP monitoring, blood examination, albumin‐creatinine ratio, carotid‐femoral pulse‐wave velocity assessment, and echocardiography for estimation of left ventricular mass index and diastolic function. Hypertensive men with ED (n=43, 24.7%) compared with those without ED were older (by 6.4 years, P

BACKGROUND: Prolonged ventricular repolarization duration confers increased risk for malignant ventricular arrhythmias. We sought to clarify the optimal method of QT/JT interval assessment in patients with complete bundle branch block (BBB). METHODS: Study patients (n = 71) were dual-chamber device recipients with baseline left or right BBB who preserved intrinsic ventricular activation during incremental atrial pacing. Patients were classified according to the presence or not of structural heart disease. The former group received chronic amiodarone therapy. QT and JT intervals were recorded at baseline heart rate of 51 ± 4 beats/min and during atrial pacing at 60, 80, and 100 beats/min. We used linear mixed-effects models to assess the effect of heart rate on the derived QTc and JTc values with the use of six different heart rate correction formulae. RESULTS: Heart rate had a significant effect on the QTc and the JTc intervals regardless of the correction formula used (P < 0.001 for all formulae). The formula of Hodges demonstrated the least variability in QTc and JTc measurements across the different heart rates in both patients groups without (F = 15.05 and F = 13.53, respectively) and with structural heart disease (F = 5.71 and F = 7.69, respectively), followed by the Nomogram and Framingham methods, whereas the uncorrected QT and JT intervals showed comparable heart rate-dependency. The application of Bazett's JTc and QTc led to the most pronounced interval variations in any case with BBB. CONCLUSIONS: The Hodges, Nomogram and Framingham correction methods provide best assessment of QT/JT intervals in BBB, whereas Bazett's formula exaggerates heart rate-dependency of ventricular repolarization intervals.

BACKGROUND: Simultaneous drug‐eluting stent (DES) and bare‐metal stent (BMS) implantation is occasionally employed in clinical practice, but its long‐term clinical and angiographic outcome is not clear. HYPOTHESIS: We aimed to describe the long‐term clinical outcome and the findings of clinically indicated coronary angiography in patients subjected to simultaneous DES and BMS implantation (“hybrid stenting”). METHODS: We identified 236 patients (mean age 62.9 ± 11.4 years, 76.7% men) who had undergone percutaneous coronary intervention with at least 1 DES and 1 BMS. At a median follow‐up of 42 months (range, 6–89 months) available in 222 patients, 13 (5.9%) patients died from cardiac causes, 13 (5.9%) experienced nonfatal acute myocardial infarction, and 24 (10.8%) experienced unstable angina. Clinically indicated repeat coronary angiography was performed in 64 patients (28.8%). RESULTS: Thirty‐one patients (14%) had target lesion revascularization (TLR). The DES demonstrated lower TLR rates (15.9% vs 36.9%, P = 0.002) and lower late loss (0.44 ± 0.5 mm vs 0.68 ± 0.7 mm, P = 0.009) compared with BMS. Use of DES was independently associated with lower risk for binary restenosis (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.19–0.89, P = 0.03) and TLR (HR: 0.26, 95% CI: 0.12–0.54, P

Congest Heart Fail. 2011;17:70–78. ©2011 Wiley Periodicals, Inc. Left ventricular (LV) response to cardiac resynchronization therapy (CRT) has typically been studied over 3- to 12-month periods. Longer-term data are unclear and response of strain parameters has not been reported. The authors evaluated long-term response with standard and strain echocardiography in 57 patients (52±15 years; 40 male; 30 white; 15 with ischemic etiology) who received a CRT-defibrillator between January 2004 and December 2005. Median ejection fraction (EF) at baseline was 22% (17%–25%). Global longitudinal, radial, and circumferential strain were −6.5% (−5.0% to −8.4%), 10.4% (6.9%–15.1%), and −7.6% (−5.5% to −10.8%), respectively. After a median of 42 months, EF increased by 5% (−1% to 15%; P

Background: There is a continuing debate about the optimal method for QT interval adjustment to heart rate changes. We evaluated the heart rate dependence of QTc intervals derived from five different QT correction methods. Methods: Study patients (n = 123, age 68 ± 11 years) were dual-chamber device recipients with baseline normal or prolonged QT interval who had preserved intrinsic ventricular activation with narrow QRS complexes. Patients were classified to either Normal-QT (n = 69) or Prolonged-QT (n = 54) groups. Serial QT intervals were recorded at baseline (52 ± 3 beats per minute) and following atrial pacing stages at 60, 80, and 100 beats per minute. The QTc formulae of Bazett, Fridericia, Sagie-Framingham, Hodges, and Karjalainen-Nomogram were applied to assess the effect of heart rate on the derived QTc values by using linear mixed-effects models. Results: Heart rate had a significant effect on QTc regardless of the formula used (P < 0.05 for all formulae). The Bazett's formula demonstrated the highest QTc variability across heart rate stages (highest F values) in both patient groups (in the total cohort, F = 175.9). In the following rank order, the formulae Hodges, Karjalainen-Nomogram, Sagie-Framingham, and Fridericia showed similar QTc heart rate dependence at both slower and faster heart rates in both patient groups (F = 21.8, 25.6, 28.8, 36.9, in the total cohort, respectively). Conclusions: Of the studied QTc formulae, the Bazett appeared the most heart rate dependent. Our results suggest the use of Hodges and the Karjalainen-Nomogram secondly to ensure least heart rate dependence of QTc intervals in patients with either normal or prolonged repolarization. (PACE 2010; 553–560)

Aims Cardiac death remains the principal cause of mortality in β-thalassemia major (β-TM). Echocardiography may provide additional information, incremental to haematological profile, both for guiding chelation therapy and to assess prognosis. Methods and results Between 1993 and 1995, 36 patients with β-TM and normal cardiac function and 25 normal volunteers underwent evaluation using resting and dobutamine stress echocardiography (DSE). Dobutamine stress echocardiography was performed at baseline and repeated after 2 years. The primary endpoint was cardiac mortality. During a 12-year observation period, seven patients (19%) died from heart failure. All seven deaths occurred among the cohort of 12 patients with median ferritin concentrations ≥2800 ng/mg. In addition, a resting left ventricular ejection fraction (LVEF), 60% was also associated with increased late mortality. In multivariate analysis, increased serum ferritin levels and reduced LVEF but not DSE or other haematological variables were independent survival determinants. Conclusion Resting LVEF provides prognostic information that is additional to ferritin levels among patients with β-TM.

BACKGROUND Both heart rate irregularity during chronic atrial fibrillation (AF) and ventricular desynchronization imposed by ventricular pacing may compromise ventricular function. We investigated whether heart rhythm regularization achieved through ventricular overdrive pacing (VP) gives additional benefit over rate control alone in patients with AF. METHODS We studied 27 patients (mean age 72 +/- 7 years) with AF and normal left ventricular (LV) systolic function who were implanted with a common VVIR pacemaker. Cardiac function was assessed by using serial echocardiographic conventional, tissue Doppler imaging (TDI) and color M-Mode (CMM) examinations, together with B-type natriuretic peptide (BNP) measurements. Baseline data were obtained during AF (mean heart rate 58 +/- 5 beats/minute) with the pacemakers programmed to ventricular mere back-up pacing. These data were compared to the corresponding measurements following a 2-week VP period after the devises had been programmed to a lower rate of 70 beats/min, ensuring most of the time continuing VP. RESULTS Continuous VP compared to AF, reduced the LV cardiac index (2.28 +/- 0.44 l/min/m(2) vs 2.33 +/- 0.39 l/min/m(2), P < 0.05), increased the LV end-systolic volume (38 +/- 14 mL vs 35 +/- 11 mL, P < 0.05), and decreased the TDI-derived systolic and diastolic mitral velocity (8.1 +/- 1.8 cm/s vs 8.3 +/- 1.6 cm/s, and 8.1 +/- 1.8 cm/s vs 8.3 +/- 1.6 cm/s, respectively, both P < 0.05) and the CMM-derived transmitral early diastolic flow propagation velocity (37.6 +/- 9.2 vs 41.5 +/- 9.7, P < 0.05). Following VP, both ratios E/Ea and E/Vp showed a trend toward increase (P = NS), whereas BNP rose up to 25.5% (median value, from 111 pg/mL to 165 pg/mL, P < 0.01). CONCLUSION VP may be considered disadvantageous compared to slower AF.

Background: Ventricular desynchronization imposed by permanent dual-chamber ventricular pacing (VDD) may compromise ventricular function. Methods: We investigated the impact of background VDD pacing on the right and left ventricular (LV) function on 129 clinically stable outpatients (mean age 69 ± 10) implanted chronically with a dual-chamber pacemaker or an automatic defibrillator by using echocardiographic techniques including tissue doppler imaging (TDI) and color M-mode (CMM) examinations, and B-type natriuretic peptide (BNP) measurements. Patients were divided into two groups of normal (n = 65) or impaired (n = 64) LV systolic function (ejection fraction 63 ± 6% and 38 ± 10%, respectively) according to clinical and echocardiographic criteria. Each patient group included two subgroups on the basis of the underlying permanent and atrial-synchronized heart rhythm: either intrinsic ventricular activation (IVA) or VDD pacing. Results: The BNP levels (mean, 95% CI) of patients with impaired LV systolic function were approximately threefold higher than those of patients with normal LV systolic function [189 (145–245) pg/mL vs 65 (50–85) pg/mL, P < 0.0001], but did not differ between subgroups of patients with IVA vs VDD pacing. By two-way analysis of variance and analysis of covariance, and after adjustment for age and gender, significant VDD pacing effects were found in terms of lower E/A ratio (P < 0.05) and increased LV end-systolic volume (P < 0.05). VDD pacing did not significantly affect the BNP levels and the LV filling pressures, as determined by the E/Ea and E/Vp ratios. Conclusions: Long-term VDD pacing may not be harmful in clinically stable patients with normal or moderately reduced LV systolic function.

Hyperventilation is well known to affect the electrocardiogram (ECG) in subjects without heart disease and produce spasm in patients with variant angina. The autonomic nervous system is thought to play a significant role in these effects. However, the normal hemodynamic response to hyperventilation is not well defined. We subjected 369 healthy volunteers (200 men, 169 women) to prolonged hyperventilation (30 respirations for 5 min and 10 min recovery) under continuous ECG monitoring and to exercise testing. Heart rate (HR), systolic and diastolic blood pressures (SBP, DBP) and rate-pressure product were recorded. Hyperventilation resulted in an immediate (within the first min), significant increase in HR by 27.4%, a further small increase at min 2 of hyperventilation, and a subsequent small decrease in HR at mins 3-5. An immediate drop of HR by 20.1% was observed with discontinuation of hyperventilation. Apart from a slightly higher HR increase in men, a similar pattern of HR changes was found in both genders. On multivariate analysis, younger age, absence of smoking, and male gender were associated with a higher HR increase with hyperventilation (p < 0.0001, p < 0.0001, and p < 0.001, respectively). SBP and DBP increased with hyperventilation, with their highest value at min 5 of hyperventilation and a subsequent drop to baseline levels. Age and gender did not affect the degree and pattern of BP changes. Absence of smoking and the presence of hypertension were associated with a higher SBP with hyperventilation (p < 0.003 and p < 0.007). The rate-pressure product increased by 43.6% with hyperventilation, a change that was only 19.1% of the respective rate-pressure product observed with exercise. Hyperventilation results in significant HR and BP increases, changes that are influenced by age, gender, smoking, and hypertension. Our study could serve as a standard for comparison of the hyperventilation effects in different disease states.

Drug-Induced QTc Interval Assessment. Introduction: There is debate on the optimal QT correction method to determine the degree of the drug-induced QT interval prolongation in relation to heart rate (ΔQTc). Methods: Forty-one patients (71 ± 10 years) without significant heart disease who had baseline normal QT interval with narrow QRS complexes and had been implanted with dual-chamber pacemakers were subsequently started on antiarrhythmic drug therapy. The QTc formulas of Bazett, Fridericia, Framingham, Hodges, and Nomogram were applied to assess the effect of heart rate (baseline, atrial pacing at 60 beats/min, 80 beats/min, and 100 beats/min) on the derived ΔQTc (QTc before and during antiarrhythmic therapy). Results: Drug treatment reduced the heart rate (P < 0.001) and increased the QT interval (P < 0.001). The heart rate increase shortened the QT interval (P < 0.001) and prolonged the QTc interval (P < 0.001) by the use of all correction formulas before and during antiarrhythmic therapy. All formulas gave at 60 beats/min similar ΔQTc of 43 ± 28 ms. At heart rates slower than 60 beats/min, the Bazett and Framingham methods provided the most underestimated ΔQTc values (14 ± 32 ms and 18 ± 34 ms, respectively). At heart rates faster than 60 beats/min, the Bazett and Fridericia methods yielded the most overestimated ΔQTc values, whereas the other 3 formulas gave similar ΔQTc increases of 32 ± 28 ms. Conclusions: Bazett's formula should be avoided to assess ΔQTc at heart rates distant from 60 beats/min. The Hodges formula followed by the Nomogram method seem most appropriate in assessing ΔQTc. (J Cardiovasc Electrophysiol, Vol. 21, pp. 905-913, August 2010)

Although laser thermal angioplasty (LTA) with a laser heated metal probe has been tolerated in diseased human coronary arteries, definition of a safety threshold is lacking. Determination of safer operation parameters for coronary LTA using a new “over the wire” 1.3-mm laser probe catheter was attempted in seven normal pigs in which platelets were labeled with indium-III. Argon laser power of 10 watts was used for 1, 2, 3, and 5 seconds. Macroscopic findings, platelet deposition and histologic changes were compared between the laser treated coronary segments and controls, the nonheated laser probe, and the wire alone segments. After 1-second LTA, there was no vessel perforation or occlusive thrombi and only infrequent nonocclusive thrombi; platelet deposition was minimal; and histologic alterations rare and superficial. These findings were comparable to controls, the nonheated laser probe, and the wire alone segments. In contrast, vessels treated for 2, 3, and 5 seconds had more frequent perforation, and occlusive and nonocclusive thrombi that was accompanied by platelet deposition significantly greater than vessels treated with LTA for I second. A deep histologic injury was present in most of these segments. Additionally, the safety of laser delivery of I second repeated for five times was tested in two additional pigs. On macroscopic and histologic analysis the incidence of vessel perforation, occlusive and nonocclusive thrombi appeared slightly less when compared to the 2-, 3-, and 5-second LTA groups, and more than the 1-second LTA group. Platelet deposition was lower than the 2-, 3-, and 5-second LTA groups, and higher than the 1-second pulse group. Thus, 1-second pulses are the threshold for safe application of LTA in normal swine coronary arteries. LTA for longer periods of energy delivery is accompanied by significant platelet deposition and high rates of thrombi formation focclusive and nonocclusive) and vessel wall perforation. Repetitive short 1-second periods of laser energy delivery do produce an accumulative injury but to a less extent than single pulses. This mode of laser energy delivery could possibly improve the safety for human LTA.

Impaired diastolic function has been described in healthy elderly subjects. Pulmonary blood volume (PBV) changes with exercise have been associated with left ventricular dysfunction, but not directly related to diastolic abnormalities. Exercise-induced relative changes in PBV were measured using gated blood pool imaging with count density comparisons over the lung in 20 healthy volunteers: 13 elderly, age 76 +/- 5 years and seven young, age 27 +/- 4 years. Serial (first exercise stage, peak exercise, and post exercise) PBV ratios were measured and correlated to peak early filling rate, peak late filling rate, and percent atrial filling obtained from the resting left ventricular time-activity curve analysis. PBV ratios tended to be higher in elderly subjects, but reached significance only at the first stage of exercise (1.04 +/- 0.07 vs. 0.93 +/- 0.10, p less than 0.01). Significant correlations were found between PBV ratios at first exercise stage and peak early filling rate (r = -0.64), peak late filling rate (r = 0.47), and percent atrial filling (r = 0.48). A significant correlation was found between PBV changes at peak exercise and resting diastolic parameters. Exercise-induced PBV changes are associated with left ventricular diastolic dysfunction at rest. Diastolic abnormalities of the aged heart may explain the differential PBV response early into exercise between young and elderly healthy subjects.