Dobutamine Stress Cardiac MRI in Pediatric Patients with Suspected Coronary Artery Disease.

Following current practice, pediatric patients with treated congenital coronary malformations or acquired coronary disease undergo Cardio-Pulmonary Exercise Test (CPET), stress Echocardiography and Electrocardiography (sEcho, sEKG), and Coronary Angiography (CA). Stress cMRI can assess cardiac function, myocardial viability, and stress/rest perfusion deficit-without radiation exposure, general anesthesia, and hospitalization-in a single non-invasive exam. The aim of our pilot study is to assess the feasibility and diagnostic accuracy of Dobutamine stress cMRI compared to the current procedures (sEcho, CPET, CA). The prospective study is focused on pediatric patients, at risk for or with previously diagnosed coronary artery disease: d-looped TGA after arterial Switch, Kawasaki disease, and anomalous origin of left coronary artery from pulmonary artery (ALCAPA) after coronary artery reimplantation. We have compared the results of MRI coronary angiography, and Dobutamine stress cMRI with traditional tests. All these diagnostic exams were acquired in a timeframe of 3 month, in a blinded fashion. All the 13 patients (age: 12 ± 2 years, median 12,7 y) recruited, completed the study without major adverse events. The mean heart rate-pressure product was 25,120 ± 5110 bpm x mm Hg. The target heart rate of 85% of the maximal theoretical was reached by 10 (77%) patients. The comparison between cardiac MRI coronarography versus the gold standard Coronary Angiography to identify the patency of the origin and the proximal pathway of the coronary arteries shows a sensitivity of 100% (confidence interval: 2,5-100%), specificity 92% (confidence interval: 64-100%). The stress test was well tolerated for the 77% of the patients and completed by the totality of patients (Table 3). Three patients (23%) had mild symptoms: nausea, vomiting, or general discomfort. In pediatric patients with a potential or definite diagnosis of coronary artery disease, stress cMRI combines an effective assessment of proximal coronary arteries anatomy with cardiac function, myocardial perfusion, and viability in a single examination. Stress cMRI can be proposed as alternative, standalone test.

DATA in BRIEF of: Interventional Cardiac Catheterization in Neonatal Age: Results in a Multi-centre Italian Experience.

A comprehensive description of morbidity and mortality as well as risk factors of interventional cardiac catheterization performed in neonatal age was reported in our paper recently published on the International Journal of Cardiology (IJCA28502; PII: S0167-5273(20)30384-3; DOI: 10.1016/j.ijcard.2020.04.013). Eight Italian high-volume centres of Paediatric Cardiology were involved in this observational, retrospective data collection and analysis. In this dataset, clinical and procedural characteristics of 1423 newborns submitted to 1551 interventional cardiac catheterization procedures were analyzed. Primary outcomes were considered procedure and in-hospital mortality as well as major adverse event and procedural failure rates. Secondary outcomes were considered minor adverse events and need for blood transfusion. Targets of this data analysis were: 1) to evaluate the overall major risk factors of interventional cardiac catheterization; 2) to identify the most hazardous interventional procedures; 3) to assess possible trends of individual procedures as well as their outcome over time; 4) to find possible relationships between the volume activity of any centre and the procedure and follow-up outcome. In particular, this Data in Brief companion paper aims to report the specific statistic highlights of the multivariable analysis (binary logistic regression) used to assess the impact of any potential risk factors on the type of procedure over a short-term follow-up.

Interventional cardiac catheterization in neonatal age: results in a multicentre Italian experience.

BACKGROUND: Despite recent technical advances, interventional cardiac catheterization is still challenging in neonatal age and no specific data concerning early outcome are so far published in literature. METHODS: Neonatal trans-catheter cardiac interventions performed in high-volume Italian referral centers were retrospectively analyzed. Primary outcomes were procedural major adverse events, in-hospital mortality and procedural failure. Secondary outcomes were minor adverse events and need for blood transfusion. RESULTS: From January 2000 to December 2017, 1423 newborns (mean weight 3.0 ± 0.6 kg, range 1.0-5.8; median age 2.0 days) underwent interventional cardiac catheterization. Overall, global procedure adverse event rate and in-hospital mortality were 10.2% and 5.2%, respectively. At multi-variable analysis, primary composite outcome was significantly related to low-weight (<2.5 kg) (p < 0.01) and younger age (≤7 days) (p < 0.01) at the procedure, prematurity (p < 0.01), uni-ventricular physiology (p < 0.01), associated genetic syndromes (p < 0.01) and procedure risk category (p < 0.01). No relationship between volume of activity of any single center and procedure outcome was found. Over time, a trend toward an increased number of procedures and their complexity was recorded. Trans-catheter management of cardiac malformations with critical, duct-dependent pulmonary blood flow by arterial duct stenting or right ventricular outflow tract stenting showed the highest increase. CONCLUSIONS: Interventional cardiac catheterization is relatively safe and feasible in neonatal age. Peri-natal age, low weight, uni-ventricular physiology and genetic syndromes still significantly contribute to procedural morbidity and in-hospital mortality of this approach.

Ambrisentan use for pulmonary arterial hypertension in a post-authorization drug registry: The VOLibris Tracking Study.

BACKGROUND: The VOLibris Tracking (VOLT) Study was an open-label, prospective, observational, multicenter, post-marketing registry program designed to more fully characterize the safety profile of ambrisentan for the treatment of pulmonary arterial hypertension (PAH). The key outcome was the incidence of aminotransferase elevations >3× the upper limit of normal (ULN). METHODS: In total, 999 patients from 115 centers in 15 countries, who were prescribed ambrisentan for the treatment of PAH (Functional Class II and III) between 30 June 2008 and 13 May 2011, were enrolled. Of these, 238 had PAH associated with connective tissue disease (PAH-CTD) and 220 had no prior PAH-specific therapy. Routine clinical monitoring data were collected by physicians. RESULTS: The incidence of both alanine and aspartate aminotransferase events (>3× ULN) was 0.02 per patient-year (95% confidence interval 0.015 to 0.027). Similar results were reported for the PAH-CTD and PAH-specific-therapy-naive subgroups. Overall, 514 (52%) patients reported treatment-emergent adverse events of special interest, most commonly edema/fluid retention (249, or 25%) and anemia (143, or 14%). CONCLUSIONS: Data from the VOLT study indicate no new ambrisentan-related safety signals. Ambrisentan was not associated with increases in liver function test abnormalities above the assumed background incidence of 1.5% per year, and the observed safety profile of ambrisentan was consistent with previously published data.

Prenatal Echocardiographic Assessment of Foramen Ovale Appearance in Fetuses with D-Transposition of the Great Arteries and Impact on Neonatal Outcome.

INTRODUCTION: Neonates with D-transposition of the great arteries (dTGA) may die at birth because of the inadequate intracardiac mixing due to a misdiagnosed restrictive foramen ovale. We reviewed our experience in echocardiographic assessment and perinatal management of fetuses with dTGA searching for new features that may predict the need for urgent balloon atrial septostomy (BAS) immediately after birth. PATIENTS AND METHODS: We included fetuses diagnosed with dTGA between January 2000 and December 2014. We assessed pre- and postnatal appearance of the foramen ovale, ductus arteriosus and pulmonary veins. Both the diagnostic findings at the time of last prenatal echocardiogram and those findings deriving from a retrospective reevaluation of stored videos were considered. BAS was defined as urgent if performed in neonates with restrictive foramen ovale and severe hypoxemia. RESULTS: We reviewed 40 fetuses with dTGA. 20/40 fetuses received urgent BAS at birth. Not only the restrictive but also the hypermobile and the redundant appearance of the foramen ovale was significantly associated with urgent BAS (p < 0.0001, p = 0.002 and p = 0.0001, respectively). CONCLUSIONS: Prenatal evaluation of the foramen ovale appearance in fetuses with dTGA is still challenging. Based on our experience, also the redundant foramen ovale appearance may need urgent BAS at birth.

Sometimes they come back: recurrent noncardiac right-to-left shunt after percutaneous patent foramen ovale closure.

: An increasing number of patients are being evaluated for percutaneous patent foramen ovale (PFO) closure to prevent recurrent cerebrovascular events, but debate still exists on therapeutic indications and off-label closure device implantation. Pulmonary arteriovenous fistulas (PAVFs) are a rare and heterogeneous malformation prevalently associated with Rendu-Osler-Weber syndrome, and may mimic PFO right-to-left shunt (RLS), leading to unnecessary interventions and in some cases to relapses. Residual shunt is increasingly being observed both after PFO closure and PAVF embolization, even at long-term follow-up, with unclear clinical relevance. This instrumental and possibly therapeutic failure could lie in the presence of pulmonary microfistulas, either pre-existing or following the intervention. Hence, if RLS persists after optimal device placement and reasonable endothelialization time, the presence of a PAVF should be assumed and investigated; if RLS recurs after previous, negative echocontrast studies, presence of device-related complications or pulmonary microfistulas should be taken into consideration.

Neurohormonal activation and pharmacological inhibition in pulmonary arterial hypertension and related right ventricular failure.

During the last decade, hyperactivity of the sympathetic nervous and renin-angiotensin-aldosterone systems (SNS and RAAS, respectively) has repeatedly been related to the pathophysiology of pulmonary arterial hypertension (PAH) and PAH-related right ventricular failure (PAH-RVF), raising the question of whether neurohormonal inhibition may be indicated for these conditions. Experimental data indicate that the RAAS may be involved in pulmonary vascular remodeling, which is in fact halted by RAAS antagonism. Favorable actions of ß-blockers on the pulmonary vasculature have also been described, even if information about ß-adrenergic receptors in PAH is lacking. Furthermore, the available evidence suggests that stimulation of the pressure-overloaded RV by the SNS and RAAS is initially compensatory, but becomes maladaptive over time. Consistently, RV reverse remodeling has been shown in PAH animal models treated with either ß-blockers or RAAS inhibitors, although important differences with human PAH may limit the translational value of these findings. Only few observational studies of neurohormonal antagonism in PAH and PAH-RVF have been published. Nonetheless, ß-blockers on top of specific therapy appear to be safe and possibly also effective. The combination of mineralocorticoid receptor and endothelin-A receptor antagonists may result in an additive effect because of a positive pharmacodynamic interaction. While neurohormonal inhibitors cannot be recommended at present for treatment of PAH and PAH-RVF, they are worth being further investigated.

Recurrent and Residual Shunts After Patent Foramen Ovale Closure: Results From a Long-Term Transcranial Doppler Study.

OBJECTIVES: Assess the evolution of right-to-left shunt (RLS) after transcatheter patent foramen ovale (PFO) closure. BACKGROUND: Despite the high number of interventional procedures performed worldwide, limited systematic data on the long-term abolition of RLS after percutaneous closure are available. METHODS: All patients treated at our Institution between February 2001 and July 2009 were included in this single center, prospective study, and were asked to repeat late contrast transcranial Doppler (cTCD). Rate of complete closure, residual RLS (i.e., a shunt that persists after closure), and recurrent RLS (i.e., a shunt that reappears after a previous negative cTCD) was assessed. RESULTS: Long-term follow-up was completed in 120 patients (56% male). RLS was still detectable 4.9 ± 2.3 years (range 1.3-10.3) after the procedure in 55 patients; 20 (17%) had residual RLS and 35 (29%) had recurrent RLS. Multivariate analysis revealed that significant predictors of residual RLS included post-procedural shunt at transesophageal echocardiography (OR 3.07, 95%CI 0.97-9.7), use of a bigger device (35 vs 25 mm, OR 3.85, 95%CI 1.22-12.2) and length of follow-up (OR 0.75, 95%CI 0.57-0.98), while only length of follow-up (OR 0.77, 95%CI 0.62-0.95) was associated with recurrent RLS. Neurological recurrences (1 stroke, 6 transient ischemic attacks) were equally distributed between the groups. CONCLUSION: A significant number of recurrent and residual shunts may be observed by cTCD up to 5 years after PFO closure. Management of late RLSs includes periodic re-evaluation, exclusion of device-induced complications or secondary sources of RLS, and optimization of antithrombotic treatment with or without a second intervention.

Controversies in pulmonary hypertension due to left heart disease.

Left heart failure is currently the most prevalent cause of pulmonary hypertension (PH) worldwide and this is due mainly to the increased left ventricular and pulmonary venous pressures seen in this condition. Still, a quota of patients with left heart failure will have a pulmonary arterial disease "disproportionate" to the initial increase of left-sided pressures. Whatever the mechanism involved, the appearance of PH is a powerful marker, as it determines decreased exercise tolerance and survival. To date, all trials using therapies approved for pulmonary arterial hypertension (PAH) failed to demonstrate a benefit in the context of heart failure (HF) without or with PH. In addition, the comparison among studies is limited by relevant differences in definitions, methodology, and timing of assessment. A novel rigorous hemodynamic classification based on the diastolic pulmonary gradient has been recently proposed to better characterize this form of PH. This will promote uniformity in patient populations and end-points for future clinical trials.

[Invasive intracoronary imaging in ischemic heart disease]. / Imaging coronarico invasivo e cardiopatia ischemica.

In the last years, both the increase in percutaneous coronary revascularization and the instance of more reliable and individualized treatments have led interventional cardiologists to seek for a valuable adjunct to angiography in order to improve assessment and treatment of atherosclerotic coronary disease. Intravascular ultrasound (IVUS) allows precise tomographic measurement of lumen area, plaque size, and, to some extent, composition, with low risks and affordable costs. It is not yet clear whether routine use of IVUS provides a middle-to-long-term benefit in prevention of recurrent cardiovascular events. This review reports the main studies on IVUS imaging, underlining impact of ultrasound in the development of contemporary percutaneous revascularization techniques.

[Patent foramen ovale and migraine: a causal or casual relationship?]. / Forame ovale pervio ed emicrania: relazione causale o casuale?

The occlusion of a patent foramen ovale (PFO) is one of the most promising and controversial issues of interventional cardiology, with an increasing number of procedures, indications and scientific publications. Although this procedure is considered relatively feasible and efficacious, complications may occur, and the balance between risks and benefits is not always favorable. Data on long-term safety and efficacy are also lacking. From cryptogenic stroke in young patients, indications for occlusion have been extended to include patients with drug-refractory migraine. In this setting, the prevalence of PFO is higher than in the general population, suggesting a possible pathogenetic role. Pathophysiology of this condition and evidence to support occlusion of PFO are incomplete, but a trend towards improving has been reported in many retrospective studies. The only randomized study for migraine benefits in PFO occlusion (MIST) has failed to show a reduction in frequency and intensity of attacks. Selection criteria for patients who will most probably benefit from occlusion are needed. The aim of this brief analysis is to focus the pathophysiological and diagnostic issues on migraine, evaluate their relation with PFO, and review studies to outline percutaneous closure indications.