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Cardiovascular magnetic resonance (CMR) and computed tomography (CCT) are advanced imaging modalities that recently revolutionized the conventional diagnostic approach to congenital heart diseases (CHD), supporting echocardiography and often replacing cardiac catheterization. This is the second of two complementary documents, endorsed by experts from the Working Group of the Italian Society of Pediatric Cardiology and the Italian College of Cardiac Radiology of the Italian Society of Medical and Interventional Radiology, aimed at giving updated indications on the appropriate use of CMR and CCT in different clinical CHD settings, in both pediatrics and adults. In this article, support is also given to radiologists, pediatricians, cardiologists, and cardiac surgeons for indications and appropriateness criteria for CMR and CCT in the most referred CHD, following the proposed new criteria presented and discussed in the first document. This second document also examines the impact of devices and prostheses for CMR and CCT in CHD and additionally presents some indications for CMR and CCT exams when sedation or narcosis is needed., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

High blood pressure (BP) or hypertension is a well known risk factor for developing heart attack, stroke, atrial fibrillation and renal failure. Although in the past hypertension was supposed to develop at middle age, it is now widely recognized that it begins early during childhood. As such, approximately 5-10% of children and adolescents are hypertensive. Unlike that previously reported, it is now widely accepted that primary hypertension is the most diffuse form of high BP encountered even in paediatric age, while secondary hypertension accounts just for a minority of the cases. There are significant differences between that outlined by the European Society of Hypertension (ESH), the European Society of Cardiology (ESC), and the last statement by the American Academy of Pediatrics (AAP) concerning the BP cut-offs to identify young hypertensive individuals. Not only that, but the AAP have also excluded obese children in the new normative data. This is undoubtedly a matter of concern. Conversely, both the AAP and ESH/ESC agree that medical therapy should be reserved just for nonresponders to measures like weight loss/salt intake reduction/increase in aerobic exercise. Secondary hypertension often occurs in aortic coarctation or chronic renal disease patients. The former can develop hypertension despite early effective repair. This is associated with significant morbidity and is arguably the most important adverse outcome in about 30% of these subjects. Also, syndromic patients, for example those with Williams syndrome, may suffer from a generalized aortopathy, which triggers increased arterial stiffness and hypertension. This review summarizes the state-of-the-art situation regarding primary and secondary paediatric hypertension., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

The Coronavirus disease 2019 (COVID-19) pandemic has thoroughly and deeply affected the provision of healthcare services worldwide. In order to limit the in-hospital infections and to redistribute the healthcare professionals, cardiac percutaneous intervention in Pediatric and Adult Congenital Heart Disease (ACHD) patients were limited to urgent or emergency ones. The aim of this article is to describe the impact of the COVID-19 pandemic on Pediatric and ACHD cath laboratory activity during the so-called 'hard lockdown' in Italy. Eleven out of 12 Italian institutions with a dedicated Invasive Cardiology Unit in Congenital Heart Disease actively participated in the survey. The interventional cardiology activity was reduced by more than 50% in 6 out of 11 centers. Adolescent and ACHD patients suffered the highest rate of reduction. There was an evident discrepancy in the management of the hard lockdown, irrespective of the number of COVID-19 positive cases registered, with a higher reduction in Southern Italy compared with the most affected regions (Lombardy, Piedmont, Veneto and Emilia Romagna). Although the pandemic was brilliantly addressed in most cases, we recognize the necessity for planning new, and hopefully homogeneous, strategies in order to be prepared for an upcoming new outbreak., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

: The recent outbreak of 2019 severe acute respiratory syndrome coronavirus-2 is having major repercussions on healthcare services provision in Italy and worldwide. Data suggest the virus has a strong impact on the cardiovascular system, and cardiac imaging will play an important role in patients affected by coronavirus disease-2019. Although paediatric patients are mildly affected, they represent a clear accelerator in spreading the virus, and healthcare workers are at higher risk of infection. The aim of this position paper is to provide clinical recommendation regarding the execution of imaging investigations for the cardiac diagnostic work-up of paediatric patients with suspected or confirmed infection.

Background: The arterial switch operation (ASO) is nowadays the standard procedure for the repair of dextro-transposition of the great arteries (d-TGA). Reduced exercise capacity, coronary artery abnormalities, and reversible myocardial perfusion defects have been demonstrated in patients who have undergone ASO. Despite this, indices of systolic function, assessed by standard echocardiography, are within the normal range. Speckle-tracking echocardiography (STE) can detect early subclinical myocardial abnormalities in several diseases even in the presence of normal left ventricular (LV) ejection fraction., Aim: To assess LV systolic myocardial deformation and torsion in asymptomatic ASO patients with normal LV ejection fraction (≥55%) by using STE., Methods: We studied 62 asymptomatic patients (26 women) who have undergone single-stage ASO for simple d-TGA, aged 8.5 ± 5.7 years, with a normal LV ejection fraction (≥55%); 31 age and sex comparable controls (14 women), aged 7.9 ± 4.9 years., Results: In patients who have undergone ASO, global LV longitudinal strain was significantly lower than that in controls (-19.2 ± 2.9% vs. -22.7 ± 2.4%, respectively, P < 0.0001). Longitudinal deformation was significantly impaired in the anterior and both anterior and posterior septal walls. In patients who have undergone ASO global circumferential strain and LV torsion were similar to controls. At multivariate analysis global LV longitudinal strain was significantly correlated only with age at surgery (P = 0.005)., Conclusion: We demonstrated a significant reduction in longitudinal myocardial deformation correlated with the age at surgical repair, despite a normal LV ejection fraction, in the largest series of asymptomatic ASO patients by using STE. Our findings suggest early (≤7 days) operation on d-TGA patients and continued monitoring of ventricular function by STE.

Background: The right heart is a major determinant of prognosis in cardiac transplant recipient patients., Aim: To investigate right ventricular morphology and function and their relationship with exercise capacity in cardiac transplant recipient patients using standard tranthoracic echocardiography and a new three-dimensional echocardiographic software adapted for right ventricular analysis., Methods: One hundred fifteen relatively stable cardiac transplant recipient patients (71 men; 58.3 ± 5.8 years; 7.8 ± 4.5 years after transplantation) and 80 healthy age-comparable and sex-comparable controls underwent standard echocardiography, tissue Doppler imaging (TDI), and three-dimensional echocardiography, focused on the right ventricular analysis. Along with left heart parameters, right ventricular measurements included end-diastolic diameters at basal and mid-cavity level; base-to-apex length; tricuspid annulus plane systolic excursion (TAPSE); TDI right ventricular systolic peak velocity (Sm); and three-dimensional ejection fraction. Using the peak systolic tricuspid regurgitation velocity (TRV) and the end-diastolic pulmonary regurgitation velocity, the modified Bernoulli equation was used to calculate the pulmonary artery systolic (PASP) and diastolic pressures. Pulmonary artery vascular conductance (PAVC) was estimated by left ventricular stroke volume/4 × (TRV - pulmonary regurgitation velocity)., Results: Left ventricular diameters and ejection fraction did not significantly differ between the two groups, whereas mass index was increased in cardiac transplant recipient patients (P < 0.01). Right ventricular diameters were significantly increased (P < 0.001), whereas TAPSE and right ventricular Sm were significantly lower in cardiac transplant recipient patients. Conversely, in cardiac transplant recipient patients, three-dimensional right ventricular ejection fraction (RVEF) was not significantly reduced (P < 0.001), whereas both PASP and PAVC were impaired. By multivariable analysis, age at transplantation (P < 0.01) and pulmonary artery mean pressure (P < 0.001) were the only independent determinants of right ventricular diameters and RVEF in cardiac transplant. Furthermore, RVEF measured by real-time three-dimensional echocardiography was a powerful independent determinant of functional capacity in cardiac transplant recipient patients., Conclusion: Despite the reduction of right ventricular performance along the long axis suggested by TAPSE and right ventricular Sm, the increased right ventricular diameters along with absence of a decrease in three-dimensional RVEF support the hypothesis of geometrical rather than functional changes of the right ventricle in cardiac transplant recipient patients.

BACKGROUND: Right ventricular pacing has been the treatment of choice in patients with congenital complete atrioventricular block (CAVB). However, the effect of chronic right ventricular pacing on left ventricular function in young patients is still controversial. AIM: The aim of the study was to assess the change in left ventricular systolic function in young patients (age ≤20 years) paced for isolated CAVB and to identify possible predictors of left ventricular systolic dysfunction. METHODS: We studied 55 young patients who underwent permanent right ventricular pacemaker implantation for CAVB in the absence of significant structural heart disease. We excluded patients affected by any condition known to affect left ventricular function. Echocardiographic data prior to and after pacemaker implantation were obtained. RESULTS: The mean age at the time of pacemaker implantation was 20 months, range 2.3-72 months. The mean duration of follow-up was 94.86 (range: 2-268 months). Chronic right ventricular pacing affected left ventricular shortening fraction (LVSF) significantly (pre = 37.8 ± 7.8 vs. post = 32.8 ± 5.5%, P = 0.0036). In 14 patients (25.4%), LVSF decreased by at least 7% (group A). The only parameter studied able to significantly discriminate the two groups was a better baseline LVSF in group A (baseline LVSF: 42.1 ± 5.2 vs. 32.2 ± 2.2%, P = 0.019; cut-off value >39%, P <0.0001; area under the curve = 0.887). CONCLUSION: Chronic right ventricular pacing in young patients without significant structural heart disease is responsible for a significant reduction in left ventricular systolic function, especially in patients with a good baseline LVSF. These patients need close follow-up not only for pacing parameters but also for left ventricular functional evaluation.

Background: Although there have been several studies about the impact of obesity on left-ventricular mass (LVM) and remodeling and their influence on cardiovascular morbidity and mortality, no studies are available on the best echocardiographic technique to study them. In addition, the role of systemic hypertension on LVM in obese adolescents has not been adequately investigated., Aims: To compare LVM and remodeling pattern assessed by M-mode, two-dimensional (2D) and three-dimensional (3D) echocardiography in obese adolescents, and to correlate LVM with 24-h ambulatory blood pressure measurements., Methods: We studied 120 adolescents: 86 obese patients by M-mode, 2D and 3D echocardiography and 34 normal individuals by echo and magnetic resonance imaging (MRI)., Results: In normal individuals LVM was assessed by 3D echo and had the strongest correlation to MRI. In obese adolescents left-ventricular geometry was abnormal in 27 patients (31%) by 3D echo, in 21 patients (24%) by 2D echo and in 43 patients (50%) by M-mode. Mean SBP was significantly related to relative wall thickness, body mass index (BMI) and LVM/h evaluated by 3D echo [r=0.52 (P<0.0001), r=0.36 (P=0.004) and r=0.28 (P=0.03), respectively]. However, at a multivariate analysis, BMI showed a stronger correlation with LVM/h assessed by 3D compared to mean SBP (r=0.44 and P=0.001 vs. r=0.26, P=0.1)., Conclusions: In young patients LVM assessed by 3D echo had the strongest correlation to MRI compared to 2D and M-mode echo. In obese adolescents, 3D echo showed left-ventricular remodeling in 31% with LVM more significantly correlated with BMI compared to mean SBP.

Objectives: To detect right ventricular myocardial function in dilated cardiomyopathy (DCM) using two-dimensional strain echocardiography (2DSE) and to evaluate the relationship between right ventricular dysfunction and response to cardiopulmonary exercise test (CPET)., Methods: Seventy-five DCM patients (44 idiopathic and 31 ischemic) without clinical signs of right ventricular failure underwent standard echo, 2DSE analysis of right ventricle and bicycle CPET., Results: The two groups were comparable for clinical and standard two-dimensional echocardiographic and Doppler variables, except for right ventricular diameters that were mildly increased in patients with idiopathic DCM. Right ventricular global longitudinal strain (RV GLS) and regional peak myocardial right ventricular strain were significantly impaired in patients with idiopathic DCM compared with ischemic DCM (both P<0.001). A significant correlation was detectable among RV GLS and VO2 peak percentage (r= -0.65, P<0.0001), VE/VCO2 slope (r=0.35, P<0.01), maximum work rate percentage (r= -0.55, P<0.001) and peak circulatory power (r=0.53, P<0.001). These correlations with RV GLS remained significant even in multivariate analysis., Conclusion: 2DSE represents a promising noninvasive technique to assess right ventricular myocardial function in patients with DCM. Reduced right ventricular myocardial deformation is related to decreased ability to perform aerobic exercise and work rate, and to impaired ventilatory response.

We describe a rare case of double-outlet left ventricle, ventricular septal defect, and subpulmonary valve stenosis surgically corrected by Rastelli procedure, developing severe homograft obstruction with right ventricular dilation and extensive hypertrabeculation/noncompaction during follow-up. We briefly discuss the cause diagnosis, and clinical significance of right ventricular hypertrabeculation/noncompaction.

Introduction: Congenital heart diseases are the most common prenatal and postnatal malformations. Nowadays, fetal echocardiography is a widely practiced technique; however, the impact of prenatal diagnosis on prognosis of the newborns affected by congenital heart disease remains uncertain., Objective: To assess the outcome and the changes in the spectrum of prenatally detected congenital heart disease in our tertiary care centre in 12 years of activity (1995-2006)., Methods and Results: We detected 705 congenital heart diseases: 32% (223) were associated with extracardiac or chromosomal anomalies or both, and 68% (482) were isolated. Termination of pregnancy was chosen in 81% for associated anomalies and 37% for isolated anomalies (P<0.001). Of these, more than one-third occurred in hypoplasic left heart cases. The general survival rate was 72%; it was significantly lower in the group with associated heart diseases (46 vs. 80%, P<0.001). Over 12 years we noticed a reduction in the number of multimalformed fetuses and of the hypoplasic left heart cases, and a higher number of aortic arch anomalies detected. During the past 6 years of activity the survival rate obtained has significantly increased (55 to 84%, P<0.05), the termination rate has significantly decreased (35 to 14%, P<0.001) and the number of neonatal deaths has significantly decreased (39 to 10%, P<0.001)., Conclusion: The survival and the voluntary termination of fetuses with prenatally detected congenital heart diseases are strongly influenced by disease severity and by associated extracardiac or chromosomal anomalies, or both. Over 12 years, the spectrum of fetal congenital heart disease has changed and their outcome has significantly improved.

Aortic valve stenosis is a common disease. Despite this, the diagnosis may often be missed; a significant proportion of patients are still identified at post-mortem examination, and 5% of operations are performed at end stage. Unrecognized aortic valve stenosis is an important cause of anesthetic mortality. One reason for failing to make a diagnosis is that the clinical signs can be difficult to interpret due to the confounding association with arterial hypertension, coronary artery disease and systemic arteriosclerosis, potentially blunting the effects of aortic valve stenosis on the circulation. Moreover, most patients with aortic valve stenosis have a long asymptomatic period and may not seek medical attention. In patients with severe, symptomatic, calcific aortic valve stenosis, aortic valve replacement is the only effective treatment; much evidence suggests that it should be offered to patients regardless of age, after appropriate clinical evaluation. Doppler echocardiography plays a pivotal role in confirming the diagnosis of aortic valve stenosis in assessing the severity of the disease and, ultimately, in giving prognostically relevant information. Moreover, echocardiography is suitable for monitoring of disease progression and left ventricular function in these patients, and is of fundamental support for clinical follow-up. Accurate noninvasive quantification of aortic valve stenosis is, however, a technically demanding and time-consuming procedure, with several potential pitfalls. Considering the frequency and importance of aortic valve stenosis, a comprehensive echocardiographic study should be offered and carefully performed in all patients with noteworthy murmurs and repeated regularly (at appropriate time intervals), together with clinical review, in patients in whom aortic valve stenosis has been diagnosed.

With the growing prevalence of obesity, scientific interest in the biology of adipose tissue has been extended to the secretory products of adipocytes, since they have been shown increasingly to affect several aspects of the pathogenesis of obesity-related diseases. Until relatively recently, the role of adipose tissue itself in the development of obesity and its consequences was considered to be a passive one. It is now clear that, in addition to storing energy in the form of triglycerides, adipocytes also secrete a large variety of proteins, including cytokines, chemokines and hormone-like factors. This production of proatherogenic chemokines by adipose tissue is of particular interest, since their local secretion, for example by perivascular adipose depots, may provide a novel mechanistic link between obesity and associated vascular complications.

Functional mitral regurgitation (FMR) is a common finding in patients with ischemic or nonischemic dilated cardiomyopathy as a complication of left ventricular (LV) dysfunction and remodeling associated with a fibrotic remodeling response of mitral leaflets to abnormal valvular loading. Although mitral valve tenting is the main determinant of FMR, clinical and experimental observations suggest that intraventricular delay could be a potential co-determinant of FMR. LV dyssynchrony can potentially contribute to FMR by several mechanisms, such as creating an uncoordinated regional LV mechanical activation in segments supporting the papillary muscles, determining diastolic mitral regurgitation, reducing the sphincteric function of the mitral annulus, and decreasing the efficiency of LV contraction and closing forces. Cardiac resynchronization therapy has been demonstrated to reduce FMR with correction of some of the underlying pathophysiological mechanisms. The present review article focuses on the role of mechanical dyssynchrony as a pathophysiological determinant of FMR, and on the potential role of cardiac resynchronization therapy as a therapeutic option for treatment of FMR in patients with severe heart failure and advanced LV dysfunction.

Objective: The present study aimed to evaluate the management of fetal cardiac dysrhythmias based on prior identification of the underlying electrophysiological mechanism., Methods: We studied 36 consecutive fetuses with cardiac dysrhythmia. Rhythm diagnosis was based on M-mode, pulsed wave Doppler and tissue Doppler imaging (TDI). Only fetuses with: (i) incessant tachycardia (> 12 h) and mean ventricular rate > 200 beats/min, (ii) signs of left ventricular dysfunction, or (iii) hydrops, were treated using oral maternal drug therapy., Results: The mean gestational age at diagnosis was 24.3 +/- 4.5 weeks. Twenty-one fetuses had tachycardia with a 1: 1 atrial-ventricular (AV) conduction. Based on ventricular-atrial interval, prenatal diagnosis was: permanent junctional reciprocating (n = 6), atrial ectopic (n = 6) or atrial-ventricular re-entry tachycardia (n = 9). One had atrial flutter, one ventricular tachycardia and four congenital AV block. Nine showed premature atrial or ventricular beats. Fifteen fetuses with incessant tachycardia, left ventricular dysfunction or hydrops were prenatally treated with maternal administration of digoxin, sotalol or flecainide. The total success rate (sinus rhythm or rate control) was 14/15 (93%). Seven fetuses were hydropics. Three of these died (one at 28 weeks of gestation, two in the first week of life). The prenatal diagnosis of dysrhythmia was confirmed at the birth in 31 of 35 live-born. No misdiagnosis was made using TDI. At 3 +/- 1.1-year follow-up, 33/35 children were alive and well., Conclusions: Fetal echocardiography could clarify the electrophysiological mechanism of fetal cardiac dysrhythmias and guide the therapy.

Doppler echocardiography is a fundamental instrument to understand heart damage during essential arterial hypertension. Left ventricular (LV) hypertrophy may also be conveniently studied in its morphological and functional aspects by ultrasound application. Echocardiography can also provide important morphological and functional information in hypertensive patients for therapeutic management and prognostic stratification. In recent years, echocardiography has been enriched by very refined techniques that are capable of studying the physiopathological intramyocardial phenomena: (i) tissue Doppler (which studies intramyocardial velocities and time intervals and allows the analysis of strain and strain rate); (ii) integrated backscatter (which analyzes variations of myocardial reflectivity in decibels); (iii) transthoracic Doppler derived coronary flow reserve (which quantifies the vasodilator response of coronary velocities to a hyperaemic stimulation); (iv) myocardial echo-contrast-echocardiography (which studies the kinetics of ultrasound contrast microbubbles at the intramyocardial level); and (v) real-time three-dimensional (3-D) echocardiography [which allows a more precise evaluation of left ventricular (LV) volumes and LV mass]. These new methodological approaches have recently been used in the hypertensive clinical setting to provide a deeper knowledge of the complex physiopathological and histopathological mechanisms underlying the modifications induced by arterial hypertension at the myocardial tissue level (myocytes, collagen, microcirculation). This review shows the advancement of high-tech ultrasound applied to hypertensive heart disease, pointing out limitations and incremental potentialities in comparison with conventional echocardiography.

Objective: To study left ventricular mechanics and textural properties in patients with Williams syndrome to define the impact of left ventricular hypertrophy on the functional findings., Methods: Echocardiography was performed in 16 Williams syndrome patients (aged 1-25 years, mean 10 +/- 6 years), four with associated supravalvular aortic stenosis and seven with systemic hypertension. Fifteen age- and body surface area-matched subjects were selected as control group. Particularly, left ventricular geometry, myocardial contractility [midwall rate-corrected circumferential fiber shortening/end-systolic meridional wall stress relationship (sigmaes)] and left ventricular diastolic function (mitral flow pattern and isovolumic relaxation time) were defined. In addition, integrated backscatter (IB) analysis intensity (IntIB) and cyclic variation (CVIB) were assessed for an ultrasonic myocardial characterization., Results: Left ventricular hypertrophy was demonstrated in nine patients (56%) and abnormal left ventricular remodeling in ten patients (62%). Particularly seven of seven hypertensive patients and three of four patients with supravalvular aortic stenosis had abnormal remodeling; left ventricular geometry was normal in patients without hypertension or supravalvular aortic stenosis. In addition, midwall rate-corrected circumferential fiber shortening/(sigmaes) relationship was within the normal range in all patients. At integrated backscatter analysis, Williams syndrome patients showed, both at interventricular septum and posterior wall, reduced CVIB (9.36 +/- 2.16 versus 10.3 +/- 1.3 and 8.65 +/- 2 versus 10.5 +/- 1.1). Compared to Williams syndrome patients without left ventricular hypertrophy (7/16), those with left ventricular hypertrophy (9/16) showed decreased mitral E/A ratio (1.32 +/- 0.09 versus 1.62 +/- 0.02), increased isovolumic relaxation time (68 +/- 7 versus 53 +/- 7) and increased IntIBS at interventricular septum (-27.3 +/- 0.07 versus -34 +/- 5)., Conclusions: Our data obtained in young Williams syndrome patients show that: (i) mild left ventricular functional and textural abnormalities may be detected also in absence of significant supravalvular aortic stenosis and/or hypertension; (ii) significant left ventricular hypertrophy may develop since childhood; (iii) differences in left ventricular remodeling and/or degree of left ventricular hypertrophy may occur. Further studies are required to define the real impact of the functional abnormalities on the natural history in patients with Williams syndrome.

Echocardiography represents the non-invasive tool most commonly used in pediatric cardiology. Indeed, it enables the definition of both the morphological and functional findings in congenital heart disease (CHD), as completely as possible in almost all the cases. In comparison with adult subjects, the echocardiographic evaluation in pediatric patients requires a different approach, providing information on the heart position in the thorax, the atrial situs viscerum, the vein-atrial and the atrio-ventricular connections, the relationship between the ventricles, the ventriculo-arterial connection and the relationship of the great arteries (segmental analysis). In addition, the echocardiographic study should include a non-invasive study of ventricular function, as mandatory to warrant an optimal pre- and postoperative management in patients with CHD. The indices most commonly utilized to assess ventricular mechanics are the 'pump indices' (i.e. ejection fraction or fractional shortening). Unfortunately, they may lead to invalid data, because of their dependence on loading conditions and heart rate. As a consequence, echocardiographic indices should be used (i.e. fiber shortening or rate-corrected velocity of circumferential fiber shortening-end systolic stress relationship), which better reflect the intrinsic myocardial contractility. More recently, evidence is mounting that new echocardiographic techniques (i.e. Doppler myocardial imaging, strain/strain rate and backscatter) may offer new insights in terms of regional functional and textural findings of the myocardium. However, long-term follow-up studies will be necessary to better define their real impact in the clinical setting.

Stress echocardiography has become a common non-invasive test in patients with chest pain and known or suspected coronary artery disease, but, as with exercise electrocardiography, it shows several major limitations. Analysis of gray-scale images based on subjective visual interpretation of wall motion and thickening has considerable variability even among experts. Doppler myocardial imaging and strain rate imaging echocardiography provides additional information in comparison with conventional echocardiography. These techniques provide quantification of regional wall motion at rest and during stress. Quantification of both systolic and diastolic myocardial function by either Doppler myocardial imaging or strain rate imaging mapping during dobutamine stress test has been shown to be a feasible, accurate, non-invasive tool that should be considered to be a sensitive alternative to the present echocardiographic and scintigraphic imaging techniques for stress tests. Time consuming off-line analysis of color images is required in the present state of technology. However, these non-invasive techniques are rapidly evolving and expanding. Further refinements in signal processing and quantitative analysis are likely in the near future.