Giuseppe Pacileo

Atrial Myocardial Deformation Properties Predict Maintenance of Sinus Rhythm After External Cardioversion of Recent-Onset Lone Atrial Fibrillation A Color Doppler Myocardial Imaging and Transthoracic and Transesophageal Echocardiographic Study

Background—Accurate echocardiographic parameters to predict maintenance of sinus rhythm in patients with atrial fibrillation (AF) are poorly defined. This study was conducted to assess the atrial myocardial properties during AF through myocardial velocity, strain rate, and strain and to compare their prognostic value in maintaining sinus rhythm in patients with lone AF with standard transthoracic (TTE) and transesophageal echocardiography (TEE). Methods and Results—Sixty-five consecutive patients with lone AF for ≤3 months underwent TTE, TEE, and myocardial velocity and strain and strain rate imaging examinations before successful external cardioversion. Maintenance of sinus rhythm was assessed during a 9-month follow-up. Atrial myocardial velocity, strain, and strain rate values in AF patients were compared with those of age- and sex-matched referents. Moreover, clinical and echocardiographic parameters of patients with maintenance of sinus rhythm (MSR patients) over the 9-month follow-up period (n=25) were compared with those from patients with AF recurrence (AFR patients; n=40). Atrial myocardial properties assessed by myocardial velocity, strain rate, and strain were significantly reduced (P<0.0001) in patients (velocity, 3.2±1.4 cm/s; strain, 23.3±19%; strain rate, 2±0.9 seconds−1) compared with referents (velocity, 5.7±1.3 cm/s; strain, 92±26%; strain rate, 4.2±1.8 seconds−1). The individual predictors of sinus rhythm maintenance were atrial appendage flow velocity (MSR patients, 39±12 cm/s; AFR patients, 32±15 cm/s; P<0.01) assessed by TEE and atrial strain (MSR patients, 33±27%; AFR patients, 17±9%; P=0.0007) and strain rate (MSR patients, 2.7±1 seconds−1; AFR patients, 1.6±0.6 seconds−1; P<0.0001) peak systolic values. Atrial strain (P<0.0001; coefficient, 0.015; SE, 0.003) and strain rate (P<0.0001; coefficient, 0.372; SE, 0.075) parameters alone were confirmed as independent predictors of sinus rhythm maintenance by multivariable analysis. Conclusions—Patients with higher atrial strain and strain rate appear to have a greater likelihood of staying in sinus rhythm. If the current data are verified in future studies, then additional pharmacological therapy and maintenance of anticoagulants for a longer period may need to be considered in those with lower atrial strain and strain rate measurements.

Prevention of Sudden Cardiac Death With Implantable Cardioverter-Defibrillators in Children and Adolescents With Hypertrophic Cardiomyopathy

OBJECTIVES The aim of this study was to determine the efficacy of implantable cardioverter-defibrillators (ICDs) in children and adolescents with hypertrophic cardiomyopathy (HCM). BACKGROUND HCM is the most common cause of sudden death in the young. The availability of ICDs over the past decade for HCM has demonstrated the potential for sudden death prevention, predominantly in adult patients. METHODS A multicenter international registry of ICDs implanted (1987 to 2011) in 224 unrelated children and adolescents with HCM judged at high risk for sudden death was assembled. Patients received ICDs for primary (n = 188) or secondary (n = 36) prevention after undergoing evaluation at 22 referral and nonreferral institutions in the United States, Canada, Europe, and Australia. RESULTS Defibrillators were activated appropriately to terminate ventricular tachycardia or ventricular fibrillation in 43 of 224 patients (19%) over a mean of 4.3 ± 3.3 years. ICD intervention rates were 4.5% per year overall, 14.0% per year for secondary prevention after cardiac arrest, and 3.1% per year for primary prevention on the basis of risk factors (5-year cumulative probability 17%). The mean time from implantation to first appropriate discharge was 2.9 ± 2.7 years (range to 8.6 years). The primary prevention discharge rate terminating ventricular tachycardia or ventricular fibrillation was the same in patients who underwent implantation for 1, 2, or ≥3 risk factors (12 of 88 [14%], 10 of 71 [14%], and 4 of 29 [14%], respectively, p = 1.00). Extreme left ventricular hypertrophy was the most common risk factor present (alone or in combination with other markers) in patients experiencing primary prevention interventions (17 of 26 [65%]). ICD-related complications, particularly inappropriate shocks and lead malfunction, occurred in 91 patients (41%) at 17 ± 5 years of age. CONCLUSIONS In a high-risk pediatric HCM cohort, ICD interventions terminating life-threatening ventricular tachyarrhythmias were frequent. Extreme left ventricular hypertrophy was most frequently associated with appropriate interventions. The rate of device complications adds a measure of complexity to ICD decisions in this age group.

Leopard syndrome : Clinical diagnosis in the first year of life

LEOPARD syndrome (LS) is an autosomal dominant syndrome characterized by multiple lentigines and café‐au‐lait spots, electrocardiographic‐conduction abnormalities, ocular hypertelorism/obstructive cardiomyopathy, pulmonary stenosis, abnormalities of the genitalia in males, retardation of growth, and deafness. LS shares many features with Noonan syndrome (NS), in which lentigines and deafness are usually not present. Molecular studies have shown that LS and NS are allelic disorders, caused by different missense mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP‐2 located at chromosome 12q22‐qter. The clinical diagnosis of LS is generally difficult in the first months of life because the distinctive lentigines are generally not present at birth and develop during childhood. From January 2002 to December 2004, we suspected LS clinically in 10 patients admitted to our genetic counseling services in the first 12 months of life. A PTPN11 gene mutation was detected in 8/10 (80%) patients. In one patient without a PTPN11 mutation a subsequent clinical diagnosis of neurofibromatosis type 1 (NF1) was made, following the evaluation of the mother, who had previously undiagnosed classic NF1. The age of LS patients with PTPN11 mutation ranged between 1 and 11 months (mean age ± SD 7.5 ± 3.96 months). Review of the clinical characteristics of patients with LS confirmed by molecular study during the first year of life demonstrates that the diagnosis of LS in the first months of age can be clinically suspected in patients presenting with three main features, that is, characteristic facial features (100%), hypertrophic cardiomyopathy (HCM) (87%), and cafe‐au‐lait spots (75%). Characteristic facial features can be mild or severe, and consist of hypertelorism, downslanting palpebral fissures, ptosis, and dysmorphic ears. The clinical suspicion of LS may be confirmed by molecular screening for PTPN11 mutations. An early diagnosis of the disease is useful for the prospective care of associated medical problems and for precise genetic counseling.

Metabolic exercise test data combined with cardiac and kidney indexes, the MECKI score: A multiparametric approach to heart failure prognosis

OBJECTIVES We built and validated a new heart failure (HF) prognostic model which integrates cardiopulmonary exercise test (CPET) parameters with easy-to-obtain clinical, laboratory, and echocardiographic variables. BACKGROUND HF prognostication is a challenging medical judgment, constrained by a magnitude of uncertainty. METHODS Our risk model was derived from a cohort of 2716 systolic HF patients followed in 13 Italian centers. Median follow up was 1041days (range 4-5185). Cox proportional hazard regression analysis with stepwise selection of variables was used, followed by cross-validation procedure. The study end-point was a composite of cardiovascular death and urgent heart transplant. RESULTS Six variables (hemoglobin, Na(+), kidney function by means of MDRD, left ventricle ejection fraction [echocardiography], peak oxygen consumption [% pred] and VE/VCO2 slope) out of the several evaluated resulted independently related to prognosis. A score was built from Metabolic Exercise Cardiac Kidney Indexes, the MECKI score, which identified the risk of study end-point with AUC values of 0.804 (0.754-0.852) at 1year, 0.789 (0.750-0.828) at 2years, 0.762 (0.726-0.799) at 3years and 0.760 (0.724-0.796) at 4years. CONCLUSIONS This is the first large-scale multicenter study where a prognostic score, the MECKI score, has been built for systolic HF patients considering CPET data combined with clinical, laboratory and echocardiographic measurements. In the present population, the MECKI score has been successfully validated, performing very high AUC.

Two-dimensional strain to assess regional left and right ventricular longitudinal function in 100 normal foetuses

AIMS Previous reports have demonstrated that myocardial velocities are not sufficiently sensitive in foetal heart studies. Strain (S) imaging is a new non-invasive ultrasonic technique able to quantify regional myocardial deformation properties. Strain imaging has a superior sensitivity than myocardial velocity for non-invasive assessment of ventricular function. However, Doppler-derived strain imaging has been used to quantify myocardial deformation properties in the foetal heart with rather limited results, because of angle dependency, sensitivity to extracardiac movement, the need for good-quality images, long and time-consuming post-processing and the low reproducibility of Doppler-derived strain. Recently, a novel method for motion estimation based on two-dimensional (2D) tissue tracking strain (2D-S) echocardiography using time-domain processing has been developed, providing rapid assessment of regional myocardial strain that is independent of both cardiac translation and angle dependency, with a very good reproducibility. However, no information on 2D-S in human foetuses has so far been provided. METHODS We studied 100 consecutive normal foetuses (gestation range: 20-32 weeks; no evidence of structural cardiovascular disease by 2D echo and Doppler study) using 2D-S imaging. Left ventricle (LV) and right ventricle (RV) peak myocardial negative strain values were obtained. RESULTS Strain data were obtained from all the studied subjects, the duration of post processing was 3 +/- 2 min for each patient dataset. Peak longitudinal deformation parameters were homogeneous in all the three studied walls (strain: septum = -25 +/- 5%; lateral wall = -25 +/- 4%; RV free wall = -24 +/- 4%; P = NS). There were significant correlations between gestational age and peak longitudinal strain (P < 0.001; R: -0.73). Inter and intra-observer variability for strain was good, <3 and <6%, respectively. CONCLUSION This study demonstrated that 2D-S is a feasible and reproducible approach to assess regional ventricular function in the foetal heart, ready for the clinical application.

Right ventricular myocardial involvement in either physiological or pathological left ventricular hypertrophy: an ultrasound speckle-tracking two-dimensional strain analysis

AIMS To analyse right ventricular (RV) myocardial deformation in patients with left ventricular (LV) hypertrophy secondary to either hypertrophic cardiomyopathy (HCM) or athletes competitive endurance training. METHODS AND RESULTS Standard Doppler echo, exercise stress echo, and 2D speckle-tracking strain echocardiography (2DSE) of RV longitudinal deformation in RV septal and lateral walls were performed in 50 top-level endurance athletes and in 35 patients with HCM, all men, having evidence of LV hypertrophy. Right ventricular global longitudinal strain (GLS) was calculated by averaging local strains along the entire right ventricle. The two groups were comparable for age and blood pressure, whereas athletes showed lower heart rate and increased body surface area than HCM. Interventricular septal thickness was higher in HCM, whereas both LV and RV end-diastolic diameters (LVEDD and RVEDD) and LV stroke volume were increased in athletes. Right ventricular tricuspid annulus systolic excursion was comparable between the two groups. Conversely, RV GLS and regional peaks of RV myocardial strain were significantly impaired in patients with HCM (all P < 0.001). Multiple linear regression models detected an independent association between RV GLS and LVEDD (beta-coefficient = -0.68, P < 0.0001) in athletes, as well as an independent correlation of the same RV GLS with septal thickness (beta = 0.63, P < 0.0001) in HCM. An RV GLS cut-off value of -0.16% differentiated athletes and HCM with an 86% sensitivity and a 92% specificity. Furthermore, in the overall population, RV GLS (beta = 0.51, P < 0.0001) was a powerful independent predictor of maximal workload during exercise stress echo. CONCLUSION Right ventricular myocardial systolic deformation is positively influenced by preload increase in athletes and negatively associated with increased septal thickness in HCM. Therefore, 2DSE may represent a useful tool in the differential diagnosis between athletes heart and HCM, underlining the different involvement of RV myocardial function in either physiological or pathological LV hypertrophy.

Left ventricular myocardial velocities and deformation indexes in top-level athletes.

BACKGROUND The aim of this study was to define the range of left ventricular (LV) velocities and deformation indexes in highly trained athletes, analyzing potential differences induced by different long-term training protocols. METHODS Standard echocardiography, pulsed-wave tissue Doppler echocardiography, and two-dimensional strain echocardiography of the interventricular septum and lateral wall were performed in 370 endurance athletes and 280 power athletes. Using pulsed-wave tissue Doppler, the following parameters of myocardial function were assessed: systolic peak velocities (S(m)), early (E(m)) and late (A(m)) diastolic velocities, and the E(m)/A(m) ratio. By two-dimensional strain echocardiography, peaks of regional systolic strain and LV global longitudinal strain were calculated. RESULTS LV mass index and ejection fraction did not significantly differ between the two groups. However, power athletes showed an increased sum of wall thicknesses (P < .01) and relative wall thickness, while LV stroke volume and LV end-diastolic diameter (P < .001) were greater in endurance athletes. By pulsed-wave tissue Doppler analysis, E(m) and E(m)/A(m) at both the septal and lateral wall levels were higher in endurance athletes. By two-dimensional strain echocardiography, myocardial deformation indexes were comparable between the two groups. E(m)/A(m) ratios ≥ 1 were found in the overall population, while 90 % of athletes had an E(m) ≥ 16 cm/sec, S(m) ≥ 10 cm/sec, and global longitudinal strain ≤ -16%. Multivariate analyses evidenced independent positive association between Em peak velocity and LV end-diastolic volume (P < .001) and an independent correlation of global longitudinal strain with the sum of LV wall thicknesses (P < .005). CONCLUSIONS This study describes the full spectrum of systolic and diastolic myocardial velocities and deformation indexes in a large population of competitive athletes.

Novel insights into the role of cardiotrophin-1 in cardiovascular diseases

Cardiotrophin-1 (CT-1), a member of interleukin (IL)-6 family, was originally isolated for its ability to induce a hypertrophic response in neonatal cardiac myocytes. This cytokine mediates a pleiotropic set of growth and differentiation activities through a unique receptor system, consisting of IL-6 receptor (IL-6R) and a common signal transducer, the glycoprotein 130 (gp130). Both in humans and in mice, CT-1 mRNA has been detected in several tissues, such as liver tissue, adipose tissue, and tissues in the respiratory and nervous systems; in each of these tissues it performs different functions. Predominant actions of CT-1 are on the heart, where it is synthesized and where it provides first myocardial protection by promoting cell survival and proliferation, it carries on its haemodynamic effects and endocrine properties, and finally, it predisposes the heart to pathological conditions. The aim of this review is to describe the pathophysiological mechanisms through which CT-1 carries out its activities, especially on the heart, and its potential contribution as a disease marker in clinical cardiology. Recent studies have confirmed its active role in promoting structural changes typical of most common cardiovascular disease, such as hypertension, valve diseases, congestive heart failure, and coronary artery disease. In fact, CT-1 induces myocyte hypertrophy and collagen synthesis, thereby participating in the progression of ventricular remodelling, which results in cardiac muscle failure at the latest stage. CT-1 plasma levels are elevated in patients with hypertension and coronary artery diseases, and they are also correlated with the severity of valve diseases and heart failure. Therefore, CT-1 may represent a diagnostic, staging, and prognostic biomarker of cardiovascular diseases.

Exercise Capacity in Young Patients After Total Repair of Tetralogy of Fallot

Abstract. Tetralogy of Fallot is the most common form of cyanotic congenital heart disease. Measurement of physical activity is usually performed as a routine part of the patients cardiac evaluation. The aim of this study was to examine the exercise performance of young patients operated on for tetralogy of Fallot, assessing the possible influence of known negative prognostic factors related to the surgical repair. The study group comprised 41 consecutive patients (29 male and 12 female, ages 11.2 ± 3.9 years, range 6–16 years) operated on for tetralogy of Fallot. Patients in the study group were divided in subgroups in relation to the age of surgical intervention (before or after 2 years of life), the surgical approach (combined transatrial/transpulmonary approach or right ventriculotomy), and the presence of aortopulmonary shunts prior to performing total correction. Their data were compared with those of 33 aged-matched asymptomatic control subjects (19 male and 14 female, ages 11.9 ± 1.3 years, range 11–16 years). Blood pressure and heart rate measured at rest were similar between control and Fallot groups. A normal increase in systolic blood pressure was observed in response to exercise intensity for all subgroups. No significant difference between control and Fallot groups was found under conditions of mild or moderate exercise or for diastolic blood pressure at rest and in response to exercise. Lower maximal heart rate and systolic blood pressure values were recorded in all patients when compared with the control subjects. Significant differences in peak workload were detected between control and Fallot groups and between the control and each subgroup; however, no difference was found between subgroups. In conclusion, despite their very satisfactory clinical status, all patients showed a reduced peak workload, irrespective of the surgical approach, age at surgery, and aortopulmonary shunts prior to performing total correction.

Pulmonary stenosis and atresia with intact ventricular septum during prenatal life

To identify fetal echocardiographic characteristics predictive of perinatal outcome in cases with a prenatal diagnosis of pulmonary stenosis or pulmonary atresia.