Biallelic truncating variants in children with titinopathy represent a recognizable condition with distinctive muscular and cardiac characteristics: a report on five patients.

Background: Monoallelic and biallelic TTN truncating variants (TTNtv) may be responsible for a wide spectrum of musculoskeletal and cardiac disorders with different age at onset. Although the prevalence of heterozygous TTNtv is relatively high in the general population, cardiac phenotyping (mainly cardiomyopathies, CMPs) in biallelic titinopathy has rarely been described in children. Methods: We reviewed the medical records of pediatric patients with biallelic TTNtv and cardiac involvement. Clinical exome sequencing excluded pathogenic/likely pathogenic variants in major CMP genes. Results: Five pediatric patients (four male) with biallelic TTNtv were included. Major arthrogryposis multiplex was observed in four patients; no patient showed intellectual disability. At a cardiac level, congenital heart defects (atrial and ventricular septal defects, n = 3) and left ventricular non-compaction (n = 1) were reported. All patients had dilated cardiomyopathy (DCM) diagnosed at birth in one patient and at the age of 10, 13, 14, and 17 years in the other four patients. Heart rhythm monitoring showed tachyarrhythmias (premature ventricular contractions, n = 2; non-sustained ventricular tachycardia, n = 2) and nocturnal first-degree atrio-ventricular block (n = 2). Cardiac magnetic resonance (CMR) imaging was performed in all patients and revealed a peculiar late gadolinium enhancement distribution in three patients. HyperCKemia was present in two patients and end-stage heart failure in four. End-organ damage requiring heart transplantation (HT) was indicated in two patients, who were operated on successfully. Conclusion: Biallelic TTNtv should be considered when evaluating children with severe and early-onset DCM, particularly if skeletal and muscular abnormalities are present, e.g., arthrogryposis multiplex and congenital progressive myopathy. End-stage heart failure is common and may require HT.

Cardiac Imaging in Patients After Fontan Palliation: Which Test and When?

The Fontan operation represents the final stage of a series of palliative surgical procedures for children born with complex congenital heart disease, where a "usual" biventricular physiology cannot be restored. The palliation results in the direct connection of the systemic venous returns to the pulmonary arterial circulation without an interposed ventricle. In this unique physiology, systemic venous hypertension and intrathoracic pressures changes due to respiratory mechanics play the main role for propelling blood through the pulmonary vasculature. Although the Fontan operation has dramatically improved survival in patients with a single ventricle congenital heart disease, significant morbidity is still a concern. Patients with Fontan physiology are in fact suffering from a multitude of complications mainly due to the increased systemic venous pressure. Consequently, these patients need close clinical and imaging monitoring, where cardiac exams play a key role. In this article, we review the main cardiac imaging modalities available, summarizing their main strengths and limitations in this peculiar setting. The main purpose is to provide a practical approach for all clinicians involved in the care of these patients, even for those less experienced in cardiac imaging.

Effects of Ivabradine on Residual Myocardial Ischemia after PCI Evaluated by Stress Echocardiography.

BACKGROUND: Residual angina after PCI is a frequently occurring disease. Ivabradine improves symptoms but its role in patients without left ventricular systolic dysfunction is still unclear. The aim was to quantify the effects of ivabradine in terms of MVO2 indicators and diastolic function. METHODS: Twenty-eight consecutive patients with residual angina after PCI were randomized to ivabradine 5 mg twice/day (IG) or standard therapy (CG). All patients performed a stress echocardiography at the enrollment and after 30 days. MVO2 was estimated from double product (DP) and triple product (TP) integrating DP with ejection time (ET). Diastolic function was evaluated determining E and A waves, E' measurements, and E/E' ratio both at rest and at the peak of exercise. RESULTS: The exercise time was longer in IG 9'49″ ± 48″ vs 8'09″ ± 59″ in CG (p=0.0001), reaching a greater workload (IG 139.3 ± 13.4 vs CG 118.7 ± 19.6 Watts; p=0.003). MVO2 expressed with DP and TP was significantly higher in IG (DP: IG 24194 ± 2697 vs CG 20358 ± 4671.8, p=0.01; TP: IG 17239 ± 4710 vs CG 12206 ± 4413, p=0.007). At peak exercise, the ET was diminished in IG than CG. The analysis of diastolic function after the exercise revealed an increase of E and A waves, without difference in the E/A ratio. The E' wave was higher in IG than CG, and in the same group, the differences between baseline and peak exercise were greater (∆E'3.14 ± 0.7 vs 2.4 ± 1.13, p=0.047). The E/E' ratio was reduced in patients treated with ivabradine (IG 10.2 ± 2.0 vs CG 7.9 ± 1.6, p=0.002). CONCLUSIONS: Ivabradine seems to produce a significant improvement of ischemic threshold, chronotropic reserve, and diastolic function.

Heparins crossover in percutaneous coronary interventions: a real issue with increasing rate of transradial procedures?

AIMS: Current guidelines give a class III recommendation to the intraprocedural use of unfractionated heparin (UFH) in patients pretreated with enoxaparin. The aim of our study was to evaluate bleeding complications in patients who underwent percutaneous coronary interventions (PCIs) performed using intraprocedural crossover of heparin therapy. METHODS: We retrospectively evaluated all PCIs performed at two Italian hospitals since January 2011 to December 2013. After a propensity-matched analysis, patients were divided into two groups (with a ratio 1 : 2) according to intraprocedural crossover of heparins (from enoxaparin to UFH) (Group 1) or intraprocedural UFH alone (Group 2). The primary end-point was a haemoglobin drop of at least 3 g/dl within 48 h after the procedure. RESULTS: During the 3 years analysed, 3224 patients underwent PCI, and after the propensity analysis, 309 patients were considered eligible for our study: 104 patients in Group 1 (69 ±â€Š12 years, 78% men) and 205 patients in Group 2 (69 ±â€Š13 years, 80% men, P = NS). There were no significant differences between the two groups for BMI, periprocedural use of antiplatelet therapy, baseline haemoglobin haematocrit or platelets levels. The primary end-point did not differ between the two groups (2.9% in Group 1 and 3.4% in Group 2, P = 0.550). Also, nadir of haematocrit or haemoglobin levels did not differ between the two groups. Finally, in hospital, major adverse cardio-cerebrovascular events did not differ between the two groups (1.9% in Group 1 and 3.9% in Group 2, P = 0.50). CONCLUSION: In this retrospective analysis of a large PCI database, the 'heparins crossover' during PCI was not associated with increased bleeding risk.

Assessment of right ventricular function by three-dimensional echocardiography and myocardial strain imaging in adult atrial septal defect before and after percutaneous closure.

Real-time three-dimensional (3D) echocardiography allows us to measure right ventricular (RV) end-diastolic volume irrespective of its shape. Tissue Doppler imaging (TDI) and speckle tracking imaging (STI) are new tools to assess myocardial function. We sought to evaluate RV function by 3D echocardiography and myocardial strain imaging in adult patients with atrial septal defect (ASD) before and 6 months after transcatheter closure in order to assess the utility of these new indexes in comparison with standard two-dimensional (2D) and Doppler parameters. Thirty-nine ASD patients and 39 healthy age- and sex-matched controls were studied using a commercially available cardiovascular ultrasound system. 2D-Doppler parameters of RV function (fractional area change, tricuspid annular plane systolic excursion, myocardial performance index) were calculated. 3D RV volumes were also obtained. RV peak-systolic velocities, peak-systolic strain, and peak systolic and diastolic strain-rate were measured in the basal, mid and apical segments of lateral and septal walls in apical 4-chamber view by TDI and STI. In open ASD, RV ejection fraction (3D-RVEF) and global and regional RV longitudinal strain were significantly higher than control group and decreased significantly after closure. By multivariate analysis 3D-RVEF, apical strain and strain rate were independent predictors of functional class. ROC analysis showed 3D-RVEF and apical strain to be more sensitive predictors of unfavorable outcome after defect closure compared to 2D-Doppler indexes. 3D echocardiography and myocardial strain imaging give useful insights in the quantitative assessment of RV function in ASD patients before and after closure.

Assessment of ascending aorta wall stiffness in hypertensive patients by tissue Doppler imaging and strain Doppler echocardiography.

BACKGROUND: Aortic stiffness may be associated with an increased incidence of cardiovascular events and has been reported to be related to arterial wall motion velocities as measured by tissue Doppler imaging. OBJECTIVE: To investigate the potential clinical application of tissue Doppler imaging (TDI) for assessment of aortic function parameters in healthy and hypertensive adults. METHODS: 110 hypertensive and 80 healthy adults were examined. Pulse wave velocity (PWV) and augmentation index (Aix) were measured as standard parameters of arterial stiffness by an oscillometric system. Aortic M-mode and TDI parameters were measured. Aortic distensibility (D) and aortic stiffness index (SI) were calculated using accepted formulae. Anterior wall aortic expansion velocity (S(Ao)), acceleration time (AT(Ao)), early (E(Ao)) and late (A(Ao)) diastolic retraction velocity and peak systolic radial strain (epsilon(Ao)) were determined. Comprehensive echocardiography was performed for the assessment of left ventricular (LV) systolic/diastolic function. RESULTS: S(Ao), E(Ao) and e(Ao) were significantly lower in hypertensive subjects (p<.001, p<.001, and p<.0001, respectively). Reduced D (p<.05 vs controls) and increased PWV (p<.05 vs controls) and SI (p<.01 vs controls) were consistent with evidence of increased aortic stiffness in both male and female hypertensive patients. PWV and Aix increased and D decreased with increasing age or systolic blood pressure. Multivariate analysis showed epsilon(Ao) to be independently related (R2 = 0.63) to pulse pressure, LV mass index and diastolic function. CONCLUSION: Ascending aorta TDI provides wall velocity and strain data differentiating hypertensive from healthy adults and reflecting aortic compliance changes related to age and sex and LV diastolic function.